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Review Article Alepidea amatymbica Eckl. & Zeyh.: A Review of Its Traditional Uses, Phytochemistry, Pharmacology, and Toxicology O. A. Wintola and A. J. Afolayan Medicinal Plant and Economic Development Research Centre, Department of Botany, University of Fort Hare, Alice 5700, South Africa Correspondence should be addressed to A. J. Afolayan; [email protected] Received 6 May 2014; Accepted 16 July 2014; Published 17 August 2014 Academic Editor: Gloria Brusotti Copyright © 2014 O. A. Wintola and A. J. Afolayan. is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Alepidea amatymbica is an important medicinal plant in Southern Africa with a long history of traditional use for the management of conditions like colds, coughs, sore throat, influenza, asthma, and abdominal cramps. Despite the much acclaimed traditional uses of the plant, there is a dearth of scientific information on the review of this plant. Hence, this review is aimed at providing information on the botany, phytochemistry, pharmacology, and toxicology of A. amatymbica. is review uses all the synonyms of the plant obtained from the plant list. Google scholar, Science Direct, PubMed, and Scopus were made use of in addition to the University of Fort Hare’s online databases. All the phytochemical studies on Alepidea amatymbica obtained from the literature reported the presence of kaurene-type diterpenoids and their derivatives. Pharmacological areas identified on A. amatymbica fresh and dried extract include antibacterial, antifungal, sedative, astringent, antimalarial, anti-inflammatory, antihelminthes, antihypertensive, anti-HIV, and diuretic activities. Literature search on A. amatymbica revealed the use of cell line, brine shrimps, and rats for the determination of the toxicity in the plant. Clinical trials and product development to fully exploit the medicinal value are also required to validate its folklore use in traditional medicine. 1. Introduction e genus Alepidea is a member of the Apiaceae family, placed in the subfamily Saniculoideae, also known as the larger tinsel flower (Eng). Species from the genus have been historically important medicinal plants throughout Africa, occurring mainly in Southern Africa [1, 2]. Alepidea is a genus of 28 species of herbaceous geophytes endemic to grassland areas of Eastern and Southern Africa northwards to Kenya and Ethiopia [1, 3, 4]. Seven out of the 28 species (A. amatymbica Eckl. & Zeyh., A. natalensis Wood & Evans, A. pilifera Weimack, A. longifolia E. Mey. Ex D¨ ummer, A. setifera N.E.Br., A. comosa D¨ ummer, and A. macowanii D¨ ummer) are known to be used commonly for medicinal purposes [5, 6]. Species of the genus Alepidea are most commonly found in the grasslands of the Eastern Cape Province, Kwazulu Natal, Mpumalanga, South Africa, and other Southern Africa countries like Lesotho, Swaziland, and Zimbabwe [7–9]. Alepidea amatymbica Eckl. & Zeyh. also known as kal- moes (Afr.); Iqwili (Xhosa); ikhathazo (Zulu) is an important source of traditional medicine [10, 11]. e plant generally grows on stream banks, drainage lines, and forest margins of Northern and Southern Drakensberg Mountains of the Eastern Cape Province, Lesotho, Kwazulu Natal, Swaziland, Mpumalanga, and Northern Province extending towards Zimbabwe [12]. e plant is critically endangered in Zimbabwe [13, 14], vulnerable in Lesotho [15], and listed as at lower risk or near threatened but locally extinct in certain heavily collected areas [14, 16]. A. amatymbica is an herba- ceous perennial plant with dark green leaves arising from a single or branched rhizome. It is a robust, erect plant, up to 2 m tall in grassland; the leaves form a loose rosette with the margins of the leaves prominently toothed, each tooth ending in a bristle. e flowering stalk hollow up to two meters in height, rising above the surrounding grasses, with numerous small flowers arranged in dense, rounded heads [8]. e inflo- rescence is widely branched, with a number of small, star- shaped white flowers about 250 mm in diameter (Figure 1). A. amatymbica has a number of synonyms, namely, Alep- idea amatymbica var. amatymbica, Alepidea amatymbica Hindawi Publishing Corporation Evidence-Based Complementary and Alternative Medicine Volume 2014, Article ID 284517, 11 pages http://dx.doi.org/10.1155/2014/284517

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Page 1: Review Article Alepidea amatymbica Eckl. & Zeyh.: A Review ...downloads.hindawi.com/journals/ecam/2014/284517.pdf · A Review of Its Traditional Uses, Phytochemistry, Pharmacology,

Review ArticleAlepidea amatymbica Eckl amp Zeyh A Review of Its TraditionalUses Phytochemistry Pharmacology and Toxicology

O A Wintola and A J Afolayan

Medicinal Plant and Economic Development Research Centre Department of Botany University of Fort Hare Alice 5700 South Africa

Correspondence should be addressed to A J Afolayan aafolayanufhacza

Received 6 May 2014 Accepted 16 July 2014 Published 17 August 2014

Academic Editor Gloria Brusotti

Copyright copy 2014 O A Wintola and A J Afolayan This is an open access article distributed under the Creative CommonsAttribution License which permits unrestricted use distribution and reproduction in any medium provided the original work isproperly cited

Alepidea amatymbica is an importantmedicinal plant in SouthernAfricawith a long history of traditional use for themanagement ofconditions like colds coughs sore throat influenza asthma and abdominal cramps Despite themuch acclaimed traditional uses ofthe plant there is a dearth of scientific information on the review of this plant Hence this review is aimed at providing informationon the botany phytochemistry pharmacology and toxicology of A amatymbica This review uses all the synonyms of the plantobtained from the plant list Google scholar Science Direct PubMed and Scopus were made use of in addition to the Universityof Fort Harersquos online databases All the phytochemical studies on Alepidea amatymbica obtained from the literature reported thepresence of kaurene-type diterpenoids and their derivatives Pharmacological areas identified on A amatymbica fresh and driedextract include antibacterial antifungal sedative astringent antimalarial anti-inflammatory antihelminthes antihypertensiveanti-HIV and diuretic activities Literature search on A amatymbica revealed the use of cell line brine shrimps and rats for thedetermination of the toxicity in the plant Clinical trials and product development to fully exploit the medicinal value are alsorequired to validate its folklore use in traditional medicine

1 Introduction

The genus Alepidea is a member of the Apiaceae familyplaced in the subfamily Saniculoideae also known as thelarger tinsel flower (Eng) Species from the genus have beenhistorically important medicinal plants throughout Africaoccurring mainly in Southern Africa [1 2] Alepidea is agenus of 28 species of herbaceous geophytes endemic tograssland areas of Eastern and Southern Africa northwardsto Kenya and Ethiopia [1 3 4] Seven out of the 28 species (Aamatymbica Eckl amp Zeyh A natalensis Wood amp Evans ApiliferaWeimackA longifolia EMey ExDummerA setiferaNEBrA comosaDummer andAmacowaniiDummer) areknown to be used commonly for medicinal purposes [5 6]Species of the genus Alepidea are most commonly foundin the grasslands of the Eastern Cape Province KwazuluNatal Mpumalanga South Africa and other Southern Africacountries like Lesotho Swaziland and Zimbabwe [7ndash9]

Alepidea amatymbica Eckl amp Zeyh also known as kal-moes (Afr) Iqwili (Xhosa) ikhathazo (Zulu) is an important

source of traditional medicine [10 11] The plant generallygrows on stream banks drainage lines and forest marginsof Northern and Southern Drakensberg Mountains of theEastern Cape Province Lesotho Kwazulu Natal SwazilandMpumalanga and Northern Province extending towardsZimbabwe [12] The plant is critically endangered inZimbabwe [13 14] vulnerable in Lesotho [15] and listed asat lower risk or near threatened but locally extinct in certainheavily collected areas [14 16] A amatymbica is an herba-ceous perennial plant with dark green leaves arising from asingle or branched rhizome It is a robust erect plant up to2m tall in grassland the leaves form a loose rosette with themargins of the leaves prominently toothed each tooth endingin a bristle The flowering stalk hollow up to two meters inheight rising above the surrounding grasses with numeroussmall flowers arranged in dense roundedheads [8]The inflo-rescence is widely branched with a number of small star-shaped white flowers about 250mm in diameter (Figure 1)A amatymbica has a number of synonyms namely Alep-idea amatymbica var amatymbica Alepidea amatymbica

Hindawi Publishing CorporationEvidence-Based Complementary and Alternative MedicineVolume 2014 Article ID 284517 11 pageshttpdxdoiorg1011552014284517

2 Evidence-Based Complementary and Alternative Medicine

(a) (b)

(c) (d)

Figure 1 (a) Alepidea amatymbica Eckl amp Zeyh in its natural habitat (source httpwwwPlantzafricacom) (b) dried rhizome of Alepideaamatymbica and ((c) and (d)) Alepidea amatymbica growing in the nursery

var cordata Eckl amp Zeyh Alepidea aquatica Kuntze andEryngium amatymbica (Eckl amp Zeyh) Koso-Pol [17]

This review is aimed at gathering information onAlepideaamatymbica that covers its traditional use phytochemistrypharmacological activity and toxicology and at highlightingthe opportunities for greater development of the plantrsquosmedicinal properties at a local and international level

2 Materials and Methods

During the review all the synonyms of Alepidea amatymbica(Alepidea amatymbica var amatymbica Alepidea amatym-bica var cordata Eckl amp ZeyhAlepidea aquaticaKuntze andEryngium amatymbica (Eckl amp Zeyh) Koso-Pol) derivedfrom the plant list synonyms httpwwwtheplantlistorg[17] were employed for the literature search Key words suchas ldquobotanyrdquo ldquopharmacological effectsrdquo ldquotoxicological effectsrdquoand ldquotraditional usesrdquo of Alepidea amatymbica were used forthe literature search Searches were done on the followingdatabases Google Scholar (httpscholargooglecom) Sci-enceDirect (httpwwwsciencedirectcom) PubMed (httpwwwncbinlmnihgovpubmed) and Scopus (httpwwwscopuscom)

3 Traditional Medicinal Uses

Various ranges of traditional uses of Alepidea amatym-bica were reported in the literature from simple uses for

conditions such as malaria diarrhea to cold coughs influ-enza chest complaints and wound to complex uses for themanagement of asthma and rheumatism For asthma treat-ment grounded samples of Alepidea amatymbica rhizomeare combined with cannabis for the washing of the diviningbones [18] Our literature search identified citations fortraditional use in six countries and these countries are locatedin Southern Africa (South Africa Swaziland Lesotho andZimbabwe) and East Africa (Kenya Ethiopia) In traditionalmedicine Alepidea amatymbica is used for the treatment ofminor ailments (eg sore throat cough and influenza) andcomplications (inflammation asthma diarrhea abdominalcramps wound and rheumatism) The ethnomedical uses ofAlepidea amatymbica are listed in Table 1 In Zimbabwe Aamatymbica is considered as one of the ten most recognisedmedicinal plants locally used as a remedy for asthmainfluenza diarrhoea and abdominal cramps and to treatcolds coughs rheumatism and wounds [14 19] This speciesis highly regarded as a remedy for respiratory tract infec-tions asthma sore throat gastrointestinal complaints feverrheumatism bleedingwounds and headache and extracts arealso reported to be active against HIV [2]

31 Posology (Dosage) A amatymbica is used for the treat-ment of colds and chest complaints Watt amp Breyer-Brand-wijk [10] as well as for asthma influenza diarrhoea andabdominal cramps sore throat and rheumatism [7 12 36]For respiratory complaints (cough cold and influenza)

Evidence-Based Complementary and Alternative Medicine 3

Table 1 Traditional uses of Alepidea amatymbica Eckl amp Zeyh

Category of use Description of traditional dosage References

Cultural and dietary

The dry rhizome and roots are smoked or powdered and taken as a snuff by divinersand healers to assist in divination and communication with ancestors [20ndash22]

Smoking the roots reportedly results in mild sedation and vivid dreams [22]The dry rhizome and roots are used as a lotion to wash the divining bones [23]

Antihypertensive Fresh rhizomes [22 24]Nervousness Dry rhizome and roots [25]Antimicrobial Leaf stem rhizome and root [8 22]Diuretic effects Fresh rhizome [22 24]

Respiratory Rhizomes and roots are used for colds coughs and influenza and respiratoryailments [7 10 21 22 25 26]

Inflammatory conditions Rhizomes and roots are used for rheumatism and wounds [10 21 22]Gastrointestinal Rhizomes and roots are used for stomach [10 21 22]Purgative Rhizomes for the treatment of abdominal disorders [7 27]Mild sedation and vivid dreams Smoking the roots [20 28]Antimalaria Rhizome [29]Astringent Fresh rhizome is applied externally [7 12]

the recommended adult dose is one tablespoonful of rawor cooked rhizome and root for children one to two tea-spoonfuls according to age is sufficient Fresh or cookedrhizome and roots are chewed or sucked and fresh rhizomeis also applied externally as a styptic [7 12] The dry rhizomeand roots are smoked or powdered and taken as a snuff byunspecified diviners and healers in South Africa to assistin divination and communication with the ancestors [20]Smoke from burning of the dry plant material is inhaled anda root infusion taken orally or administered per rectum asan enema [25] Smoking the roots results in mild sedationand vivid dreams and a decoction made of the dried productis taken or fresh rhizomes are chewed It is also burnedand inhaled or administered as snuff [7 12] Zulu herbalists(Izinyanga) prescribe the plant to help prevent nervousnessin South Africa [25]

32 Contradictions Alepidea amatymbica rhizome isbelieved to be used as a diuretic by Somova et al [24] but theplant was reported by Wright et al [37] to have no diureticeffect in an overview of plants with putative diuretic effects

4 Chemical Constituents

Some of the phytochemicals isolated and characterized todate fromAlepidea amatymbica are showed in Figure 2Theseinclude kaurene-type diterpenoids and their derivatives likeent-9 (11)-dehydro-16-kauren-19-oic acid ent-16-kauren-19-oic acid wedelia seco-kaurenolide and 313-acetoxy whichis believed to constitute up to 118 of rhizome and rootdry mass [20] The activity of the medicine can most likelybe attributed to the diterpenoids it contains although theyhave not been tested individually [20] Several diterpenoidkaurene derivatives have been isolated from the rhizomesand roots of A amatymbica [30 31 38] Lipophilic extracts

of the powdered dried rhizomes of A amatymbica collectedin different localities also confirmed the presence of ent-9(11)-dehydro-16-kauren-19-oic acid (la) ent-16-kauren-19-oicacid (2a) wedelia seco-kaurenolide (3) and (4) and the 313-acetoxy derivative of 3 previously reported as constituentsof the roots and aerial parts of A amatymbica [30] Theextracts contained additional kaurene derivatives not pre-viously reported A comparative study of dichloromethaneextracts of the roots of several Alepidea species showed thepresence of kaurene derivatives in every caseThedistributionof all the major compounds found in Alepidea amatymbica issummarized in Table 2The highly resinous rhizomes containkaurene-type diterpenoids [30 31]

5 Pharmacological Reports

Different pharmacological areas were revealed in the litera-ture search on A amatymbica investigation These includeanti-inflammatory antibacterial antifungal antihelminticantimalarial antihypertensive and diuretic activities Thesummarized detail of the pharmacological studies on Aamatymbica was showed in Table 3 However there is dearthof information in literature on the pharmacological effectsof the active principles of A amatymbica Hutchings [27]reported the performance of screening tests on the basis ofpersonal communication with a pharmaceutical companyindicating the antimicrobial antihypertensive and diureticactivity [24]

51 Antimicrobial Activity Crude dichloromethane petrole-umether ethanol and aqueous rhizome extracts demonstratestrong antibacterial activity against both gram-negative andgram-positive bacteria used However the crude PE andDCM rhizome extracts exhibited the best MIC (039mgmL)against B subtilis and the rest of the extracts were shown to

4 Evidence-Based Complementary and Alternative Medicine

H3C CH2

CH2

O OH COOHOAc

Me

Me

R

R

R

SSS H

HHO2C

Ent-kaur-16-en-19-oic acid

16120572-Methoxy-ent-kaur-en-19-oic acid

15120573-Acetoxy-(mdash)-kaur-16-en-19-oic acid

Sources (ChemSpider sigma-Aldrich and Google)

Figure 2 Chemical structures of kaurene-type diterpenoids in Alepidea amatymbica

Table 2 Chemical groups part of the plant studied and isolated compounds isolated from Alepidea amatymbica Eckl amp Zeyh

Phytochemicals Compound Plant part Reference

Terpenes(kaurene-type diterpenoids)

ent-9 (11)-dehydro-16-kauren-19-oic acid Rhizomes and roots [30 31]ent-16-kauren-19-oic acid Dried rhizomes [30]wedelia seco-kaurenolide Dried rhizomes [12 30]313-acetoxy Dried rhizomes [30]

Phenolic acid Phenolic acid Rhizome [32]Rosmarinic acid 31015840-O-120573-d-Glucopyranosyl rosmarinic acid Rhizome [2]

have low activity (MIC value gt 1mgmL) [6]The dosage andMIC of the plant extract used in this study showed activityagainst the bacterial tested when compared to the controlThis suggests that the result favors its usage in traditionalmedicine for the treatment of bacterial infections

In a related work the crude extracts of the leaf stemrhizome and root of A amatymbica exhibit a range of anti-microbial properties against the following bacteria Bacilluscereus Staphylococcus epidermidis Staphylococcus aureusMicrococcus kristinae Streptococcus pyogenes Escherichiacoli Salmonella poona Serratia marcescens Pseudomonasaeruginosa and Klebsiella pneumoniaeThe acetone rhizomeextract showed better activity than others especially on Saureus and B cereus and moderate activity was recordedagainst the gram-positive bacteria tested with the exceptionofMicrococcus kristinae [8] Although the inhibitionwas highin all the parts of the plant tested the acetone and methanolstem extract showed a weak activity against Streptococcuspyogenes This result supports the use of A amatymbicain treating bacterial diseases associated with respiratorytract urinary tract and gastrointestinal tract infections Dueto lack of positive control in this work it is difficult to

draw conclusions on the study Thus further investigation isrequired to justify its traditional usage as antibacterial

The fresh and 90-day dried crude extract of the leafand rhizome extract of A amatymbica prepared in waterethanol and hexane were used in this study [9] The extractsdemonstrated anti-H pylori activity with zone of inhibitionrange of 0ndash38mm and MIC

50range of 006ndash50mgmL

respectively The antimicrobial activity was comparable withthe control antibiotics HoweverA amatymbica extracts gavea susceptibility of less than 50

The antibacterial activity also increased with storage orageing of plant material [33] Antibacterial activity is stablein dry specimens and as such may account for the factthat activity is unaffected by storage in certain instances[39] Therefore the result favors the use of the plant as anantibacterial considering the activity of the extract and thecontrol even though the dosage was not stated Hence morework is needed in the validation of the plant extract for thetreatment of bacterial infections

52 Antifungal Activity Antifungal activities of A amatym-bica have been reported [6 8] The crude extracts of the leaf

Evidence-Based Complementary and Alternative Medicine 5

Table3Ph

armacologicalinvestigationof

Alepidea

amatym

bica

Ecklamp

Zeyh

Activ

ityteste

dMod

elused

Plantp

art

usedte

sted

material

Extracttype

Dosage

Con

trol

Results

Reference

Antibacteria

l

Nutrie

ntagar

medium

was

mixed

with

extractand

bacteriasuspensio

nSpeciesstrainsB

acillus

subtilisA

TCC6051

and

Staphylococcus

aureus

ATCC

1260

0and

Escherich

iacoliAT

CC117

75andKlebsiella

pneumoniae

ATCC

13883

Rhizom

eDCM

PE

waterand

EtOHrhizom

eextracts

1mgm

LWater

andbacteriafre

ebroth(minusve)01m

gmL

neom

ycin

(+ve)

TheP

EandDCM

extracts

ofther

hizomes

exhibited

theb

estactivity

(MIC

values

of039

mgmL)

againstB

subtilis

Ther

est

ofthee

xtractssho

wedlow

activ

ity(M

ICvalues

gt1m

gmL)

[6]

Antibacteria

l

Agard

ilutio

nmetho

dswith

thefollowingorganism

sBa

cilluscereus

Staphylococcus

epidermidis

Staphylococcus

aureus

Micrococcusk

ristin

ae

Streptococcusp

yogenes

Escherich

iacoliSalm

onella

poonaSerratiamarcescens

Pseudomonas

aeruginosa

andKlebsiella

pneumoniae

Crud

eextractso

ftheleafste

m

rhizom

eandroot

Aceton

eand

methano

l1ndash10mgmL

Plates

containing

1aceton

eand

methano

lin

agar

Thea

cetone

rhizom

eextractsho

wed

bette

ractiv

itythan

others

especiallyon

Saureus

and

Bcereus

mod

eratea

ctivity

thatwas

recorded

againstthe

gram

-positive

bacteria

teste

dwith

thee

xceptio

nof

Micrococcusk

ristin

ae

[8]

Antim

icrobial

Microdilutio

nmetho

don

Mueller-Hintonbroth

SpeciesB

acillus

subtilis

Staphylococcus

aureus

Escherich

iacoliand

Klebsiella

pneumoniae

Rhizom

eand

leaf

(fresh90

days

old

andon

e-year-o

ldmaterial)were

assayed

Waterethanoland

hexane

extracts

125625313156

078039

020and

01m

gmL

Extract-frees

olutionand

ethano

lwereu

sedas

ablankcontroland

neom

ycin

(+ve)

Thew

ater

extractsof

plants

teste

dfora

ntibacteria

lactiv

ityshow

edno

activ

ity

whereas

thee

thanol

extractsgenerally

show

edan

increase

inactiv

ityTh

eantib

acteria

lactivity

increase

with

storage

orageing

ofplantm

aterial

[33]

Antim

icrobial

Agarw

elldiffu

sionmetho

dusingHpyloriino

cula

prepared

atMcFarland

rsquosturbidity

standard

2was

plated

onto

BHIa

gar

supp

lementedwith

5ho

rseb

lood

andSkirr

owrsquos

supp

lement

Rootsrhizom

esEthylacetateacetone

ethano

lmethano

landwater

100m

gmL

Clarith

romycin

and10

DMSO

wereu

sedas

positivea

ndnegativ

econtrols

respectiv

ely

Thep

lantsd

emon

strated

anti-Hpyloriactivity

with

zone

diam

eterso

finhibitio

nbetween0and

38mm

and50minim

uminhibitory

concentration

(MIC50)v

aluesranging

from

006

to50m

gmL

[9]

6 Evidence-Based Complementary and Alternative MedicineTa

ble3Con

tinued

Activ

ityteste

dMod

elused

Plantp

art

usedte

sted

material

Extracttype

Dosage

Con

trol

Results

Reference

Antim

icrobial

Agarw

elldiffu

sionmetho

dAlepidea

amatym

bica

were

investigated

against30

clinicalstrains

ofHpylori

Rootsrhizom

esEthylacetateacetone

ethano

lmethano

landwater

0002ndash50m

gmL

Referencec

ontro

lstrain

(NCT

C116

38)

Metronidazoleand

amoxicillin

wereincluded

aspo

sitivec

ontro

lantib

iotic

s

Methano

lwas

quantitatively

theb

est

solventfor

allthe

plants

whileethylacetatehadthe

lowestyieldsA

amatym

bica

gave

percentage

susceptib

ilitie

sof

lessthan

50

[9]

Antifu

ngal

Agard

ilutio

nmetho

dswith

thefollowingorganism

sAspergillus

flavus

Aspergillus

nigerand

Penicilliu

mnotatum

cultu

resw

erem

aintained

onPo

tato

Dextro

seagar

Crud

eextractso

ftheleafste

m

rhizom

eandroot

Aceton

eand

methano

l

Radialpatte

rnof

streakingof

organism

swas

used

Plates

containing

onlyPD

Aor

PDAwith

ther

espective

solvent

Diameter

ofthefun

gal

grow

thwas

measuredand

expressedas

percentage

grow

thinhibitio

nAllthe

extractsshow

edmorethan

50mycoticinhibitio

nwith

activ

ityrang

ingfro

m5139

to

8111at

5mgmLwith

ther

hizome

[8]

Antifu

ngal

Thea

ntifu

ngalactiv

ityof

thee

xtractsw

asevaluated

againstC

andida

albicans

(ATC

C10231)andfung

alcultu

rewas

prepared

inYeastM

alt(YM

)

Rhizom

eDCM

PE

waterand

EtOHrhizom

eextracts

01ndash50m

gmL

Water

andbacteriafre

ebroth(minusve)01m

gmL

neom

ycin

(+ve)

Allthee

xtractssho

wed

activ

ityagainstC

andida

albicans

[6]

Anti-infl

ammatory

Usin

gthee

nzym

ebased

cyclo

oxygenasea

ssays

COX-

1and

COX-

2Rh

izom

eDCM

PE

waterand

EtOHrhizom

eextracts

1mgmL

Water

andbacteriafre

ebroth(minusve)01m

gmL

neom

ycin

(+ve)

TheP

EandDCM

extracts

hadhigh

COX-

1activity

with

percentage

inhibitio

nsabove7

0E

thanol

extractshadinhibitio

nless

than

40

[6]

Antihypertensive

Purifi

edcompo

unds

onbloo

dpressure

andheart

rateof

anesthetized

Wistar

rats

Freshrhizom

es

Hexanee

xtractive

(AA1)

dichloromethane

extractiv

eand

methano

lextractive

ipinjectio

nof

sodium

thiopenton

e(40m

gkg

body

weight)

Chlorothiazide

Inadditio

nto

the

cardiovascular

effects

distinctdiureticand

natriuretic

effectswere

foun

d

[24]

Antiplasm

odium

Plasmodium

falciparum

strainD10

usingthe

parasitelactate

dehydrogenase(pL

DH)

assay

Who

leplant

Dichlorom

ethane

(DCM

)DCM

methano

l(M

eOH)(11)

MeO

Hand

purifi

edwater

100ndash

02120583

gmL)

Chloroqu

ined

ipho

sphate

served

asthep

ositive

control

Detectp

lant-based

antim

alarialagents

show

ingprom

ising

antip

lasm

odialactivity

with

IC50

values

ofle10gmL

[34]

Diuretic

TheL

ipschitztestwas

used

todeterm

inethe

Diuretic

andsaluretic

activ

ityin

rats

Freshrhizom

eHexaneethylacetate

extract

Thetestcom

poun

dwas

appliedorallyata

dose

of50

mgkg

Urea(

1gkgb

w)

Hydrochlorothiazide

(25m

gkg

bw)

Thed

iuretic

andnatriuretic

effectsof

thee

xtractives

werefou

ndto

besim

ilarto

thee

ffectso

fchlorothiazide

[24]

Evidence-Based Complementary and Alternative Medicine 7

Table3Con

tinued

Activ

ityteste

dMod

elused

Plantp

art

usedte

sted

material

Extracttype

Dosage

Con

trol

Results

Reference

Cardiovascular

Purifi

edcompo

unds

onbloo

dpressure

andheart

rateof

anesthetized

Wistar

rats

Purifi

edcompo

undfro

mfre

shrhizom

e

Hexanee

xtract

(AA1)

dichloromethaneand

methano

lportio

nof

AA1weres

ubjected

torepeated

flash

chromatograph

ywith

gradient

elutio

n(100ndash70

hexaneEtO

Ac)to

give

AA3a

crystalline

mixture

ofent-k

aur-en-19-oic

acident-kaura-9

(11)

16-dien-19-oicacid

and

trachyloban-19-oic

acidA

A4

16-m

etho

xy-ent-kaur-

11-en-19-oica

cid

AA511-a

cetoxy-ent-

kaur-16-en-19-oic

acidand

AA6

wedelia

seco-kaureno

lide

20mgkg

bw

intraperito

neally

Ethylene

glycol

Mod

eratebu

tsignificant

decreasin

gsysto

licbloo

dpressure

(SBP

)and

heart

rate(H

T)effectsaft

erintraperito

nealapplication

onconsciou

srats

[24]

Anti-H

IV

Extractsandtherein

subfractions

ofA

amatym

bica

werea

ssessed

inac

ellbased

assay

targetingther

eplicationof

prototypicCX

CR4-tro

pic

(NL4

-3)o

rCCR

5-tro

pic

(NL-AD87)H

IV-1str

ains

Aeria

lpartsand

roots

Aqueou

s500120583

Lof

samplea

taconcentrationof

25mgmL

Standard

retro

viral

inhibitor

Thea

ctiveing

redient

identifi

edin

thea

queous

extractd

oesn

otsupp

orta

directapplicationof

this

plantextractfortreating

HIV

infection

The

anti-HIV

activ

ityof

the

pure

compo

undwas

foun

dto

bequ

itemod

erate

[212]

Antihelminthes

Nem

atod

egrowth

agar

with

Caenorhabditiseleg

ans

varBristol(N

2)nematod

es

Freshandsto

red

leaves

androot

Ethano

l1m

gmL

Levamiso

le(+Ve

)and

nematod

eincub

ated

with

water

(minusVe

)

Onlyfre

shandsto

redwater

extractsshow

eda

significantantihelminthes

[33]

8 Evidence-Based Complementary and Alternative Medicine

Table3Con

tinued

Activ

ityteste

dMod

elused

Plantp

art

usedte

sted

material

Extracttype

Dosage

Con

trol

Results

Reference

Toxicity

Theb

acteria

lcultures

(100120583L)

werea

dded

to100120583

Lof

plantextractin

500120583

Lph

osph

ateb

uffer

and2m

Lof

agar

containing

biotin-histidine(05m

M)

Rhizom

eDCM

PE

waterand

EtOHrhizom

eextracts

50500and

5000120583gmL

4-Nitroq

uino

line-N-oxide

(4NQO)w

asused

asa

positivec

ontro

land

water

(minusve

control)

TheA

mes

testrevealed

that

none

ofthep

lant

extracts

significantly

increasedthe

numbero

fHis+

revertants

with

respecttothen

egative

control

[6]

Cytoxicity

HeLaVe

roJurkatE

61

AA-

2or

CEM-SScells

Freshrhizom

esAq

ueou

s1m

gmL

Not

stated

Thee

xtractwas

nottoxicat

anyconcentrationused

inthetest

[35]

Acutetoxicity

Evaluatio

nusingbrine

shrim

pAr

temiasalin

aintersectio

nbioassay

Freshrhizom

esHexane

Not

stated

Not

stated

Theb

rines

hrim

ptest

show

edthatthec

rude

hexane

extractshave

low

toxicitywith

LC5002

[24]

Toxicity

TheH

ippo

craticteston

rats

was

used

Freshrhizom

esIsolates

from

Alepidea

amatym

bica

Hexanee

xtractive

01m

gmL

Verapamil(10m

gkg)

Allextracts

crud

eand

purifi

edsho

wed

low

toxicityrang

ingfro

mLC

5005to

5ngmLapartfrom

AA4

andAA5

that

prod

uced

slightd

iarrheao

ndays

34and5andother

extractiv

esshow

edno

toxicityatad

oseo

f20

[24]

Evidence-Based Complementary and Alternative Medicine 9

stem rhizome and root exhibited activity against Candidaalbicans extracts and more than 50 mycotic inhibitionagainst fungal cultures [6] This study does not provide adose dependent evidence of the extract and negative controlwas not used in validating the traditional use of the plantas antifungal Also all the extracts except acetone extractshowed mycotic inhibition activity against Aspergillus flavusandAspergillus niger [8]These results validate the traditionaluses of the plant as an antifungal but no dose dependentevidencewas given in this study and positive control drugwasnot used in comparison with the extract used Therefore theantifungal activity of the extract cannot be compared with anantifungal drug

53 Antiviral Louvel et al [2] investigated the screeningactivity of the aerial part and root aqueous extract of Aamatymbica against a cell-based infection assay targeting thereplication of prototypic CXCR4-tropic (NL4-3) or CCR5-tropic (NL-AD87) HIV-1 strains designed to detect inhibitorsblocking any step of the viral life cycle The active ingredientidentified in the extract does not support a direct applicationof this plant extract for treating HIV infection The anti-HIV activity of the pure compound was found to be quitemoderate Lack of negative control and a dose dependentactivity of the extract make the antiviral activity of the extractinconclusive

54 Antihelminthes Research was undertaken using nema-tode growth agar with Caenorhabditis elegans var Bristol(N2)nematodes on the ethanol extract of the fresh and storedleaves and root ofA amatymbicaOnly fresh and storedwaterextracts showed a significant Anthelminthic [33] The resultof the study did not evaluate a dose dependent inhibitionof the extract against the worms even though the controlswere compared with the extract Further investigation isthus required to validate the use of the plant in traditionalmedicine as antihelmintic

55 Anti-Inflammatory The DCM PE water and EtOHrhizome extracts were evaluated using the enzyme basedcyclooxygenase assays COX-1 and COX-2 [6] The PE andDCM extracts had high COX-1 and COX-2 activities withpercentage inhibitions above 70 Ethanol extracts showedhigher inhibition (lt40) in COX-1 than COX-2 The waterextract on the other hand has a moderate inhibition activ-ity (40ndash60) in COX-1 and lowered in COX-2 (lt20)Despite reports on the undesirable effects of higher COX-1 inhibition as a result of its damage to the gastrointestinaltract [40] report of Mulaudzi et al [6] recorded a higherCOX-1 in both DCM and PE and a lower COX-1 inhibitionin ethanol and water The result favors the use of waterand ethanol as a solvent of extraction for this plant whenusing it against inflammation However conclusion cannotbe totally drawn on this report due to lack of negativecontrol and dosage Hence further investigation is required toprovide an evidence for its traditional use against inflamma-tion

56 Antihypertensive Hexane extractive (AA1) dichloro-methane extractive and methanol extractive of the fresh rhi-zome were investigated using purified compounds on bloodpressure and heart rate of anesthetizedWistar rats Moderatebut significant decrease in systolic blood pressure (SBP) andheart rate (HT) effects after intraperitoneal application onconscious rats was reported [24]

57 Antiplasmodium Dichloromethane (DCM) DCMmethanol (MeOH) (1 1) MeOH and purified water extractfrom the whole plant were investigated on plasmodialactivity and were found to contain plant based antimalarialagents showing promising antiplasmodial activity with IC

50

values of le10 gmL [34] This is the only study showing thedose dependent antiplasmodic activity of the plant extractin relation to the positive control Validation of the use ofthe plant in vivo is necessary to conclude the antiplasmodialactivity of A amatymbica

58 Diuretic The purified compounds of the fresh rhizomeextracted in hexaneethyl acetate of A amatymbica wereinvestigated using anesthetized Wistar rats The diuretic andnatriuretic effects of the extractives were found to be similarto the effects of chlorothiazide drug [24] The result suggeststhe inhibitory effect of the extractive of A amatymbica inreabsorption of K+ and Na+ ions suggesting the diureticand natriuretic effects of the extractives Lack of testedextractive in a dose dependent manner however negates thevalidation of the plants and the extractives for use as diuretictraditionally Further investigation is required to provideevidence for its use as a diuretic

6 Toxicological Reports

Four toxicity screens were identified in the literature Eachof the four screens tested uses crude aqueous and organicsolvents hexane extracts and extractives from the crudehexane extract and none of the reports recorded toxicity atall doses testedThe reported cytotoxicity of the fresh aqueousrhizome was investigated using HeLa Vero and Jurkat E61AA-2 or CEM-SS cells The extract was shown not to betoxic at all concentrations used in the test [35] since thedosage and controls were shown in this study in comparisonwith the control The second screens use bacterial cultures(100 120583L) in an Amen test assay which were added to 100120583L ofDCM PE water and EtOH rhizome plant extracts in 500120583Lphosphate buffer and 2mLof agar containing biotin-histidine(05mM) The Ames test revealed that none of the plantextracts significantly increased the number ofHis+ revertantswith respect to the negative control [6] The third test screenutilised the Brine Shrimp Lethal Assay (BSLA) Acute toxicityof the isolates from Alepidea amatymbica was screen againstbrine shrimp Artemia salina intersection bioassay The brineshrimp test showed that the crude hexane extracts have lowtoxicity with LC

5002 ngmL while the AA6 (wedelia seco-

kaurenolide) a derivative of A amatymbica has a low toxicityof 05 ngmL [24]The fourth screenmade use of Hippocratictest on rats with the use of hexane (AA1) extract and itrsquos

10 Evidence-Based Complementary and Alternative Medicine

extractives in dichloromethane and methanol (AA1) aftersubjection to repeated flash chromatography with gradientelution (100ndash70 hexaneEtOAc) to give AA3 a crystallinemixture of ent-kaur-en-19-oic acid ent-kaura-9 (11) 16-dien-19-oic acid and trachyloban-19-oic acid AA4 16-methoxy-ent-kaur-11-en-19-oic acid AA5 11-acetoxy-ent-kaur-16-en-19-oic acid and AA6 wedelia seco-kaurenolide All extractscrude and purified showed low toxicity ranging from 05 to5 ngmL (LC

50) apart from AA4 and AA5 that produced

slight diarrhea on days 3 4 and 5 and other extractivesshowed no toxicity at a dose of 20 [24] Apart from thestudies of Treurnicht [35] and Mulaudzi et al [6] mentionedabove the other studies do not provide sufficient evidencewith respect to the safety of A amatymbica considering theabsence of dosage used and control in their assays

7 Clinical Trials

To date there appears to be no published research indicatingthat extracts ofAlepidea amatymbica have undergone humanclinical trials

8 Conclusion

The review showed that A amatymbica has a widespread usein South Africa and other SADEC countriesThe recognitionof its ethnomedicinal usage for conditions of inflammationlike rheumatism and sore throat to usage for wounds coughasthma influenza diarrhea stomach cramps abdominal dis-orders malaria and diuretic is worth mentioningThe abilityof the extract to also restrain the growth of bacteria and fungiindicated its broad spectrum antimicrobial prospective Thepharmacological reports on A amatymbica revealed thera-peutic potential in the treatment of inflammation malariaand infectious diseases like influenza cough and diarrheaThe frequently occurring chemical constituents of Alepideaamatymbica belong to the kaurene-type diterpenoids andtheir derivatives Literature search onA amatymbica revealedthe use of cell line brine shrimps and rats for the determi-nation of the toxicity in the plant More investigations arenecessary to explore themedicinal potential of the plant in themanagement of rheumatism asthma hypertension diureticand inflammation Clinical trials and product development tofully exploit the medicinal value are also required to validateits folklore use in traditional medicine There is thereforethe need to develop the existing traditional use of this plantto amplify nutraceuticals product and commence clinicalresearch to exploit the plantrsquos novel phytochemicals

Conflict of Interests

The authors declare no conflict of interests

Acknowledgments

The authors are thankful to the Govan Mbeki Research andDevelopment Centre and the National Research Fund of theUniversity of Fort Hare South Africa

References

[1] B l Burtt ldquoUmbelliferae of southern Africa an introductionand annotated checklistrdquo Edinburgh Journal of Botany vol 48pp 133ndash282 1991

[2] S Louvel N Moodley I Seibert et al ldquoIdentification ofcompounds from the plant species Alepidea amatymbica activeagainst HIVrdquo South African Journal of Botany vol 86 pp 9ndash142013

[3] G Germishuizen N L Meyer Y Steenkamp and M KeithPlants of Southern Africa An Annotated Checklist vol 41 ofSABONET Report National Botanical Institute Pretoria SouthAfrica 2006

[4] R R Klopper P Lemmer and J Nel ldquoPteridophyta Pteridaceaecheilanthes deltoidea a new locality in Gauteng South AfricardquoBothalia vol 36 no 2 pp 173ndash174 2006

[5] Z Maksimovic S Dobric N Kovacevic and Z MilovanovicldquoDiuretic activity of Maydis stigma extract in ratsrdquo Pharmazievol 59 no 12 pp 967ndash971 2004

[6] R B Mulaudzi A R Ndhlala J F Finnie and J Van StadenldquoAntimicrobial anti-inflammatory and genotoxicity activityof Alepidea amatymbica and Alepidea natalensis (Apiaceae)rdquoSouth African Journal of Botany vol 75 no 3 pp 584ndash587 2009

[7] A de Castro and B-E van Wyk ldquoDiagnostic characters andgeographic distribution of Alepidea species used in traditionalmedicinerdquo South African Journal of Botany vol 60 no 6 pp345ndash350 1994

[8] A J Afolayan and F B Lewu ldquoAntimicrobial activity ofAlepideaamatymbicardquo Pharmaceutical Biology vol 47 no 5 pp 436ndash439 2009

[9] C Njume A A Jide and R N Ndip ldquoAqueous and organicsolvent-extracts of selected South African medicinal plantspossess antimicrobial activity against drug-resistant strainsof Helicobacter pylori inhibitory and bactericidal potentialrdquoInternational Journal of Molecular Sciences vol 12 no 9 pp5652ndash5665 2011

[10] J M Watt and M G Breyer-Brandwijik The Medicinal andPoisonous Plants of Southern and Eastern Africa E and SLivingstone London UK 2nd edition 1962

[11] B E van Wyk A de Castro P M Tilney P J D Winter andA R Magee ldquoA new species of Alepidea (Apiaceae subfamSaniculoideae)rdquo South African Journal of Botany vol 74 no 4pp 740ndash745 2008

[12] J T Mukinda and P F K Eagles ldquoThe South African Pharma-copoeia Monograph Projectrdquo Developed by South African Tra-ditional Medicines Research Group (SATMERG) and Schoolof Pharmacy University of the Western Cape (Unpublished)2010

[13] A Mapaura and J R Timberlake ldquoSouthern African plantred data listsrdquo Southern African Botanical Diversity Network(SABONET) Report 14 SABONET Pretoria South Africa

[14] A Maroyi ldquoEthnobotanical study of two threatened medicinalplants in Zimbabwerdquo International Journal of Biodiversity Sci-ence and Management vol 4 no 3 pp 148ndash153 2008

[15] S Talukdar ldquoLesothordquo in Southern African Plant Red Data ListsJ Golding Ed Southern African Botanical Diversity Network(SABONET) Report Number 14 pp 21ndash30 SABONET Preto-ria South Africa 2002

[16] R Scott-Shaw ldquoRare and threatened plants of KwaZulu-Nataland neighbouring regionsrdquo in A Plant Red Data Book p182 KwaZulu-Natal Nature Conservation Service Pietermar-itzburg South Africa 1999

Evidence-Based Complementary and Alternative Medicine 11

[17] The Plant List 2012 httpwwwtheplantlistorg[18] S Nonjinge and B B Tarr Natal National Botanical Garden

2013 httpwwwplantzafricacomplantabalipedeamathtm[19] M Gelfand S Mavi R B Drummond and B Ndemera The

Traditional Medical Practitioner in Zimbabwe Mambo PressGweru Zimbabwe 1985

[20] B E VanWyk and N Gericke rsquoPeoplersquos PlantsmdashA Guide toUseful Plants of South Africa Briza Publication Pretoria SouthAfrica 2000

[21] A Hutchings A H Scott G Lewis and A CunninghamZulu Medicinal Plants An Inventory University of Natal PressScottsville South Africa 1996

[22] B E van Wyk B van Oudtshoorn and N Gericke MedicinalPlants of South Africa Briza Publications Pretoria SouthAfrica 1997

[23] J A Guillarmod Flora of Lesotho J Cramer Lehre Germany1971

[24] L I Somova F O Shode K Moodley and Y GovenderldquoCardiovascular and diuretic activity of kaurene derivativesof Xylopia aethiopica and Alepidea amatymbicardquo Journal ofEthnopharmacology vol 77 no 2-3 pp 165ndash174 2001

[25] J Pujol NaturAfrica The Herbalists Handbook Jean PujolNatural Healers Foundation Durban South Africa 1990

[26] A Hutchings and J van Staden ldquoPlants used for stress-relatedailments in traditional Zulu Xhosa and Sotho medicine Part 1plants used for headachesrdquo Journal of Ethnopharmacology vol43 no 2 pp 89ndash124 1994

[27] A Hutchings ldquorsquoObservations on plant usage in Xhosa and Zulumedicinerdquo Bothalia vol 19 pp 225ndash235 1989

[28] J F Sobiecki ldquoA preliminary inventory of plants used forpsychoactive purposes in southern African healing traditionsrdquoTransactions of the Royal Society of SouthAfrica vol 57 pp 1ndash242002

[29] S O Bandeira F Gaspar and F P Pagula ldquoAfrican ethnobotanyand healthcare emphasis on Mozambiquerdquo PharmaceuticalBiology vol 39 pp 70ndash73 2001

[30] A Rustaiyan and A S Sadjadi ldquoKaurene derivatives fromAlepidea amatynsiardquo Phytochemistry vol 26 no 7 pp 2106ndash2107 1987

[31] C W Holzapfel B E van Wyk A de Castro W Marais andM Herbst ldquoA chemotaxonomic survey of kaurene derivativesin the genus Alepidea (Apiaceae)rdquo Biochemical Systematics andEcology vol 23 no 7-8 pp 799ndash803 1995

[32] D K Olivier B van Wyk and F R van Heerden ldquoThechemotaxonomic and medicinal significance of phenolic acidsin Arctopus and Alepidea (Apiaceae subfamily Saniculoideae)rdquoBiochemical Systematics and Ecology vol 36 no 9 pp 724ndash7292008

[33] G I Stafford A K Jager and J van Staden ldquoEffect ofstorage on the chemical composition and biological activityof several popular South African medicinal plantsrdquo Journal ofEthnopharmacology vol 97 no 1 pp 107ndash115 2005

[34] C Clarkson V JMaharaj N R Crouch et al ldquoIn vitro antiplas-modial activity of medicinal plants native to or naturalised inSouth Africardquo Journal of Ethnopharmacology vol 92 no 2-3pp 177ndash191 2004

[35] F T TreurnichtAn evaluation of the toxic and potential antiviraleffects of some plants used by South Africans for medicinalpurposes [MS thesis] University of Stellenbosch StellenboschSouth Africa 1997

[36] A Hutchings Zulu Medicinal Plants Natal University PressPietermaritzburg South Africa 1996

[37] C I Wright L van-Buren C I Kroner and M M GKoning ldquoHerbalmedicines as diuretics a reviewof the scientificevidencerdquo Journal of Ethnopharmacology vol 114 no 1 pp 1ndash312007

[38] F O Shode and B C Rogers ldquoThe chemistry of ApiaceaeIsolation and characterisation of diterpenoids and other ter-penoids from Alepidea amatymbicardquo in Proceedings of the 7thInternational Chemistry Conference in Africa Durban SouthAfrica 1998

[39] C W Fennell M E Light S G Sparg G I Stafford and JVan Staden ldquoAssessingAfricanmedicinal plants for efficacy andsafety agricultural and storage practicesrdquo Journal of Ethnophar-macology vol 95 no 2-3 pp 113ndash121 2004

[40] D Luseba E E Elgorashi D T Ntloedibe and J Van StadenldquoAntibacterial anti-inflammatory and mutagenic effects ofsome medicinal plants used in South Africa for the treatmentof wounds and retained placenta in livestockrdquo South AfricanJournal of Botany vol 73 no 3 pp 378ndash383 2007

Submit your manuscripts athttpwwwhindawicom

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ObesityJournal of

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Parkinsonrsquos Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom

Page 2: Review Article Alepidea amatymbica Eckl. & Zeyh.: A Review ...downloads.hindawi.com/journals/ecam/2014/284517.pdf · A Review of Its Traditional Uses, Phytochemistry, Pharmacology,

2 Evidence-Based Complementary and Alternative Medicine

(a) (b)

(c) (d)

Figure 1 (a) Alepidea amatymbica Eckl amp Zeyh in its natural habitat (source httpwwwPlantzafricacom) (b) dried rhizome of Alepideaamatymbica and ((c) and (d)) Alepidea amatymbica growing in the nursery

var cordata Eckl amp Zeyh Alepidea aquatica Kuntze andEryngium amatymbica (Eckl amp Zeyh) Koso-Pol [17]

This review is aimed at gathering information onAlepideaamatymbica that covers its traditional use phytochemistrypharmacological activity and toxicology and at highlightingthe opportunities for greater development of the plantrsquosmedicinal properties at a local and international level

2 Materials and Methods

During the review all the synonyms of Alepidea amatymbica(Alepidea amatymbica var amatymbica Alepidea amatym-bica var cordata Eckl amp ZeyhAlepidea aquaticaKuntze andEryngium amatymbica (Eckl amp Zeyh) Koso-Pol) derivedfrom the plant list synonyms httpwwwtheplantlistorg[17] were employed for the literature search Key words suchas ldquobotanyrdquo ldquopharmacological effectsrdquo ldquotoxicological effectsrdquoand ldquotraditional usesrdquo of Alepidea amatymbica were used forthe literature search Searches were done on the followingdatabases Google Scholar (httpscholargooglecom) Sci-enceDirect (httpwwwsciencedirectcom) PubMed (httpwwwncbinlmnihgovpubmed) and Scopus (httpwwwscopuscom)

3 Traditional Medicinal Uses

Various ranges of traditional uses of Alepidea amatym-bica were reported in the literature from simple uses for

conditions such as malaria diarrhea to cold coughs influ-enza chest complaints and wound to complex uses for themanagement of asthma and rheumatism For asthma treat-ment grounded samples of Alepidea amatymbica rhizomeare combined with cannabis for the washing of the diviningbones [18] Our literature search identified citations fortraditional use in six countries and these countries are locatedin Southern Africa (South Africa Swaziland Lesotho andZimbabwe) and East Africa (Kenya Ethiopia) In traditionalmedicine Alepidea amatymbica is used for the treatment ofminor ailments (eg sore throat cough and influenza) andcomplications (inflammation asthma diarrhea abdominalcramps wound and rheumatism) The ethnomedical uses ofAlepidea amatymbica are listed in Table 1 In Zimbabwe Aamatymbica is considered as one of the ten most recognisedmedicinal plants locally used as a remedy for asthmainfluenza diarrhoea and abdominal cramps and to treatcolds coughs rheumatism and wounds [14 19] This speciesis highly regarded as a remedy for respiratory tract infec-tions asthma sore throat gastrointestinal complaints feverrheumatism bleedingwounds and headache and extracts arealso reported to be active against HIV [2]

31 Posology (Dosage) A amatymbica is used for the treat-ment of colds and chest complaints Watt amp Breyer-Brand-wijk [10] as well as for asthma influenza diarrhoea andabdominal cramps sore throat and rheumatism [7 12 36]For respiratory complaints (cough cold and influenza)

Evidence-Based Complementary and Alternative Medicine 3

Table 1 Traditional uses of Alepidea amatymbica Eckl amp Zeyh

Category of use Description of traditional dosage References

Cultural and dietary

The dry rhizome and roots are smoked or powdered and taken as a snuff by divinersand healers to assist in divination and communication with ancestors [20ndash22]

Smoking the roots reportedly results in mild sedation and vivid dreams [22]The dry rhizome and roots are used as a lotion to wash the divining bones [23]

Antihypertensive Fresh rhizomes [22 24]Nervousness Dry rhizome and roots [25]Antimicrobial Leaf stem rhizome and root [8 22]Diuretic effects Fresh rhizome [22 24]

Respiratory Rhizomes and roots are used for colds coughs and influenza and respiratoryailments [7 10 21 22 25 26]

Inflammatory conditions Rhizomes and roots are used for rheumatism and wounds [10 21 22]Gastrointestinal Rhizomes and roots are used for stomach [10 21 22]Purgative Rhizomes for the treatment of abdominal disorders [7 27]Mild sedation and vivid dreams Smoking the roots [20 28]Antimalaria Rhizome [29]Astringent Fresh rhizome is applied externally [7 12]

the recommended adult dose is one tablespoonful of rawor cooked rhizome and root for children one to two tea-spoonfuls according to age is sufficient Fresh or cookedrhizome and roots are chewed or sucked and fresh rhizomeis also applied externally as a styptic [7 12] The dry rhizomeand roots are smoked or powdered and taken as a snuff byunspecified diviners and healers in South Africa to assistin divination and communication with the ancestors [20]Smoke from burning of the dry plant material is inhaled anda root infusion taken orally or administered per rectum asan enema [25] Smoking the roots results in mild sedationand vivid dreams and a decoction made of the dried productis taken or fresh rhizomes are chewed It is also burnedand inhaled or administered as snuff [7 12] Zulu herbalists(Izinyanga) prescribe the plant to help prevent nervousnessin South Africa [25]

32 Contradictions Alepidea amatymbica rhizome isbelieved to be used as a diuretic by Somova et al [24] but theplant was reported by Wright et al [37] to have no diureticeffect in an overview of plants with putative diuretic effects

4 Chemical Constituents

Some of the phytochemicals isolated and characterized todate fromAlepidea amatymbica are showed in Figure 2Theseinclude kaurene-type diterpenoids and their derivatives likeent-9 (11)-dehydro-16-kauren-19-oic acid ent-16-kauren-19-oic acid wedelia seco-kaurenolide and 313-acetoxy whichis believed to constitute up to 118 of rhizome and rootdry mass [20] The activity of the medicine can most likelybe attributed to the diterpenoids it contains although theyhave not been tested individually [20] Several diterpenoidkaurene derivatives have been isolated from the rhizomesand roots of A amatymbica [30 31 38] Lipophilic extracts

of the powdered dried rhizomes of A amatymbica collectedin different localities also confirmed the presence of ent-9(11)-dehydro-16-kauren-19-oic acid (la) ent-16-kauren-19-oicacid (2a) wedelia seco-kaurenolide (3) and (4) and the 313-acetoxy derivative of 3 previously reported as constituentsof the roots and aerial parts of A amatymbica [30] Theextracts contained additional kaurene derivatives not pre-viously reported A comparative study of dichloromethaneextracts of the roots of several Alepidea species showed thepresence of kaurene derivatives in every caseThedistributionof all the major compounds found in Alepidea amatymbica issummarized in Table 2The highly resinous rhizomes containkaurene-type diterpenoids [30 31]

5 Pharmacological Reports

Different pharmacological areas were revealed in the litera-ture search on A amatymbica investigation These includeanti-inflammatory antibacterial antifungal antihelminticantimalarial antihypertensive and diuretic activities Thesummarized detail of the pharmacological studies on Aamatymbica was showed in Table 3 However there is dearthof information in literature on the pharmacological effectsof the active principles of A amatymbica Hutchings [27]reported the performance of screening tests on the basis ofpersonal communication with a pharmaceutical companyindicating the antimicrobial antihypertensive and diureticactivity [24]

51 Antimicrobial Activity Crude dichloromethane petrole-umether ethanol and aqueous rhizome extracts demonstratestrong antibacterial activity against both gram-negative andgram-positive bacteria used However the crude PE andDCM rhizome extracts exhibited the best MIC (039mgmL)against B subtilis and the rest of the extracts were shown to

4 Evidence-Based Complementary and Alternative Medicine

H3C CH2

CH2

O OH COOHOAc

Me

Me

R

R

R

SSS H

HHO2C

Ent-kaur-16-en-19-oic acid

16120572-Methoxy-ent-kaur-en-19-oic acid

15120573-Acetoxy-(mdash)-kaur-16-en-19-oic acid

Sources (ChemSpider sigma-Aldrich and Google)

Figure 2 Chemical structures of kaurene-type diterpenoids in Alepidea amatymbica

Table 2 Chemical groups part of the plant studied and isolated compounds isolated from Alepidea amatymbica Eckl amp Zeyh

Phytochemicals Compound Plant part Reference

Terpenes(kaurene-type diterpenoids)

ent-9 (11)-dehydro-16-kauren-19-oic acid Rhizomes and roots [30 31]ent-16-kauren-19-oic acid Dried rhizomes [30]wedelia seco-kaurenolide Dried rhizomes [12 30]313-acetoxy Dried rhizomes [30]

Phenolic acid Phenolic acid Rhizome [32]Rosmarinic acid 31015840-O-120573-d-Glucopyranosyl rosmarinic acid Rhizome [2]

have low activity (MIC value gt 1mgmL) [6]The dosage andMIC of the plant extract used in this study showed activityagainst the bacterial tested when compared to the controlThis suggests that the result favors its usage in traditionalmedicine for the treatment of bacterial infections

In a related work the crude extracts of the leaf stemrhizome and root of A amatymbica exhibit a range of anti-microbial properties against the following bacteria Bacilluscereus Staphylococcus epidermidis Staphylococcus aureusMicrococcus kristinae Streptococcus pyogenes Escherichiacoli Salmonella poona Serratia marcescens Pseudomonasaeruginosa and Klebsiella pneumoniaeThe acetone rhizomeextract showed better activity than others especially on Saureus and B cereus and moderate activity was recordedagainst the gram-positive bacteria tested with the exceptionofMicrococcus kristinae [8] Although the inhibitionwas highin all the parts of the plant tested the acetone and methanolstem extract showed a weak activity against Streptococcuspyogenes This result supports the use of A amatymbicain treating bacterial diseases associated with respiratorytract urinary tract and gastrointestinal tract infections Dueto lack of positive control in this work it is difficult to

draw conclusions on the study Thus further investigation isrequired to justify its traditional usage as antibacterial

The fresh and 90-day dried crude extract of the leafand rhizome extract of A amatymbica prepared in waterethanol and hexane were used in this study [9] The extractsdemonstrated anti-H pylori activity with zone of inhibitionrange of 0ndash38mm and MIC

50range of 006ndash50mgmL

respectively The antimicrobial activity was comparable withthe control antibiotics HoweverA amatymbica extracts gavea susceptibility of less than 50

The antibacterial activity also increased with storage orageing of plant material [33] Antibacterial activity is stablein dry specimens and as such may account for the factthat activity is unaffected by storage in certain instances[39] Therefore the result favors the use of the plant as anantibacterial considering the activity of the extract and thecontrol even though the dosage was not stated Hence morework is needed in the validation of the plant extract for thetreatment of bacterial infections

52 Antifungal Activity Antifungal activities of A amatym-bica have been reported [6 8] The crude extracts of the leaf

Evidence-Based Complementary and Alternative Medicine 5

Table3Ph

armacologicalinvestigationof

Alepidea

amatym

bica

Ecklamp

Zeyh

Activ

ityteste

dMod

elused

Plantp

art

usedte

sted

material

Extracttype

Dosage

Con

trol

Results

Reference

Antibacteria

l

Nutrie

ntagar

medium

was

mixed

with

extractand

bacteriasuspensio

nSpeciesstrainsB

acillus

subtilisA

TCC6051

and

Staphylococcus

aureus

ATCC

1260

0and

Escherich

iacoliAT

CC117

75andKlebsiella

pneumoniae

ATCC

13883

Rhizom

eDCM

PE

waterand

EtOHrhizom

eextracts

1mgm

LWater

andbacteriafre

ebroth(minusve)01m

gmL

neom

ycin

(+ve)

TheP

EandDCM

extracts

ofther

hizomes

exhibited

theb

estactivity

(MIC

values

of039

mgmL)

againstB

subtilis

Ther

est

ofthee

xtractssho

wedlow

activ

ity(M

ICvalues

gt1m

gmL)

[6]

Antibacteria

l

Agard

ilutio

nmetho

dswith

thefollowingorganism

sBa

cilluscereus

Staphylococcus

epidermidis

Staphylococcus

aureus

Micrococcusk

ristin

ae

Streptococcusp

yogenes

Escherich

iacoliSalm

onella

poonaSerratiamarcescens

Pseudomonas

aeruginosa

andKlebsiella

pneumoniae

Crud

eextractso

ftheleafste

m

rhizom

eandroot

Aceton

eand

methano

l1ndash10mgmL

Plates

containing

1aceton

eand

methano

lin

agar

Thea

cetone

rhizom

eextractsho

wed

bette

ractiv

itythan

others

especiallyon

Saureus

and

Bcereus

mod

eratea

ctivity

thatwas

recorded

againstthe

gram

-positive

bacteria

teste

dwith

thee

xceptio

nof

Micrococcusk

ristin

ae

[8]

Antim

icrobial

Microdilutio

nmetho

don

Mueller-Hintonbroth

SpeciesB

acillus

subtilis

Staphylococcus

aureus

Escherich

iacoliand

Klebsiella

pneumoniae

Rhizom

eand

leaf

(fresh90

days

old

andon

e-year-o

ldmaterial)were

assayed

Waterethanoland

hexane

extracts

125625313156

078039

020and

01m

gmL

Extract-frees

olutionand

ethano

lwereu

sedas

ablankcontroland

neom

ycin

(+ve)

Thew

ater

extractsof

plants

teste

dfora

ntibacteria

lactiv

ityshow

edno

activ

ity

whereas

thee

thanol

extractsgenerally

show

edan

increase

inactiv

ityTh

eantib

acteria

lactivity

increase

with

storage

orageing

ofplantm

aterial

[33]

Antim

icrobial

Agarw

elldiffu

sionmetho

dusingHpyloriino

cula

prepared

atMcFarland

rsquosturbidity

standard

2was

plated

onto

BHIa

gar

supp

lementedwith

5ho

rseb

lood

andSkirr

owrsquos

supp

lement

Rootsrhizom

esEthylacetateacetone

ethano

lmethano

landwater

100m

gmL

Clarith

romycin

and10

DMSO

wereu

sedas

positivea

ndnegativ

econtrols

respectiv

ely

Thep

lantsd

emon

strated

anti-Hpyloriactivity

with

zone

diam

eterso

finhibitio

nbetween0and

38mm

and50minim

uminhibitory

concentration

(MIC50)v

aluesranging

from

006

to50m

gmL

[9]

6 Evidence-Based Complementary and Alternative MedicineTa

ble3Con

tinued

Activ

ityteste

dMod

elused

Plantp

art

usedte

sted

material

Extracttype

Dosage

Con

trol

Results

Reference

Antim

icrobial

Agarw

elldiffu

sionmetho

dAlepidea

amatym

bica

were

investigated

against30

clinicalstrains

ofHpylori

Rootsrhizom

esEthylacetateacetone

ethano

lmethano

landwater

0002ndash50m

gmL

Referencec

ontro

lstrain

(NCT

C116

38)

Metronidazoleand

amoxicillin

wereincluded

aspo

sitivec

ontro

lantib

iotic

s

Methano

lwas

quantitatively

theb

est

solventfor

allthe

plants

whileethylacetatehadthe

lowestyieldsA

amatym

bica

gave

percentage

susceptib

ilitie

sof

lessthan

50

[9]

Antifu

ngal

Agard

ilutio

nmetho

dswith

thefollowingorganism

sAspergillus

flavus

Aspergillus

nigerand

Penicilliu

mnotatum

cultu

resw

erem

aintained

onPo

tato

Dextro

seagar

Crud

eextractso

ftheleafste

m

rhizom

eandroot

Aceton

eand

methano

l

Radialpatte

rnof

streakingof

organism

swas

used

Plates

containing

onlyPD

Aor

PDAwith

ther

espective

solvent

Diameter

ofthefun

gal

grow

thwas

measuredand

expressedas

percentage

grow

thinhibitio

nAllthe

extractsshow

edmorethan

50mycoticinhibitio

nwith

activ

ityrang

ingfro

m5139

to

8111at

5mgmLwith

ther

hizome

[8]

Antifu

ngal

Thea

ntifu

ngalactiv

ityof

thee

xtractsw

asevaluated

againstC

andida

albicans

(ATC

C10231)andfung

alcultu

rewas

prepared

inYeastM

alt(YM

)

Rhizom

eDCM

PE

waterand

EtOHrhizom

eextracts

01ndash50m

gmL

Water

andbacteriafre

ebroth(minusve)01m

gmL

neom

ycin

(+ve)

Allthee

xtractssho

wed

activ

ityagainstC

andida

albicans

[6]

Anti-infl

ammatory

Usin

gthee

nzym

ebased

cyclo

oxygenasea

ssays

COX-

1and

COX-

2Rh

izom

eDCM

PE

waterand

EtOHrhizom

eextracts

1mgmL

Water

andbacteriafre

ebroth(minusve)01m

gmL

neom

ycin

(+ve)

TheP

EandDCM

extracts

hadhigh

COX-

1activity

with

percentage

inhibitio

nsabove7

0E

thanol

extractshadinhibitio

nless

than

40

[6]

Antihypertensive

Purifi

edcompo

unds

onbloo

dpressure

andheart

rateof

anesthetized

Wistar

rats

Freshrhizom

es

Hexanee

xtractive

(AA1)

dichloromethane

extractiv

eand

methano

lextractive

ipinjectio

nof

sodium

thiopenton

e(40m

gkg

body

weight)

Chlorothiazide

Inadditio

nto

the

cardiovascular

effects

distinctdiureticand

natriuretic

effectswere

foun

d

[24]

Antiplasm

odium

Plasmodium

falciparum

strainD10

usingthe

parasitelactate

dehydrogenase(pL

DH)

assay

Who

leplant

Dichlorom

ethane

(DCM

)DCM

methano

l(M

eOH)(11)

MeO

Hand

purifi

edwater

100ndash

02120583

gmL)

Chloroqu

ined

ipho

sphate

served

asthep

ositive

control

Detectp

lant-based

antim

alarialagents

show

ingprom

ising

antip

lasm

odialactivity

with

IC50

values

ofle10gmL

[34]

Diuretic

TheL

ipschitztestwas

used

todeterm

inethe

Diuretic

andsaluretic

activ

ityin

rats

Freshrhizom

eHexaneethylacetate

extract

Thetestcom

poun

dwas

appliedorallyata

dose

of50

mgkg

Urea(

1gkgb

w)

Hydrochlorothiazide

(25m

gkg

bw)

Thed

iuretic

andnatriuretic

effectsof

thee

xtractives

werefou

ndto

besim

ilarto

thee

ffectso

fchlorothiazide

[24]

Evidence-Based Complementary and Alternative Medicine 7

Table3Con

tinued

Activ

ityteste

dMod

elused

Plantp

art

usedte

sted

material

Extracttype

Dosage

Con

trol

Results

Reference

Cardiovascular

Purifi

edcompo

unds

onbloo

dpressure

andheart

rateof

anesthetized

Wistar

rats

Purifi

edcompo

undfro

mfre

shrhizom

e

Hexanee

xtract

(AA1)

dichloromethaneand

methano

lportio

nof

AA1weres

ubjected

torepeated

flash

chromatograph

ywith

gradient

elutio

n(100ndash70

hexaneEtO

Ac)to

give

AA3a

crystalline

mixture

ofent-k

aur-en-19-oic

acident-kaura-9

(11)

16-dien-19-oicacid

and

trachyloban-19-oic

acidA

A4

16-m

etho

xy-ent-kaur-

11-en-19-oica

cid

AA511-a

cetoxy-ent-

kaur-16-en-19-oic

acidand

AA6

wedelia

seco-kaureno

lide

20mgkg

bw

intraperito

neally

Ethylene

glycol

Mod

eratebu

tsignificant

decreasin

gsysto

licbloo

dpressure

(SBP

)and

heart

rate(H

T)effectsaft

erintraperito

nealapplication

onconsciou

srats

[24]

Anti-H

IV

Extractsandtherein

subfractions

ofA

amatym

bica

werea

ssessed

inac

ellbased

assay

targetingther

eplicationof

prototypicCX

CR4-tro

pic

(NL4

-3)o

rCCR

5-tro

pic

(NL-AD87)H

IV-1str

ains

Aeria

lpartsand

roots

Aqueou

s500120583

Lof

samplea

taconcentrationof

25mgmL

Standard

retro

viral

inhibitor

Thea

ctiveing

redient

identifi

edin

thea

queous

extractd

oesn

otsupp

orta

directapplicationof

this

plantextractfortreating

HIV

infection

The

anti-HIV

activ

ityof

the

pure

compo

undwas

foun

dto

bequ

itemod

erate

[212]

Antihelminthes

Nem

atod

egrowth

agar

with

Caenorhabditiseleg

ans

varBristol(N

2)nematod

es

Freshandsto

red

leaves

androot

Ethano

l1m

gmL

Levamiso

le(+Ve

)and

nematod

eincub

ated

with

water

(minusVe

)

Onlyfre

shandsto

redwater

extractsshow

eda

significantantihelminthes

[33]

8 Evidence-Based Complementary and Alternative Medicine

Table3Con

tinued

Activ

ityteste

dMod

elused

Plantp

art

usedte

sted

material

Extracttype

Dosage

Con

trol

Results

Reference

Toxicity

Theb

acteria

lcultures

(100120583L)

werea

dded

to100120583

Lof

plantextractin

500120583

Lph

osph

ateb

uffer

and2m

Lof

agar

containing

biotin-histidine(05m

M)

Rhizom

eDCM

PE

waterand

EtOHrhizom

eextracts

50500and

5000120583gmL

4-Nitroq

uino

line-N-oxide

(4NQO)w

asused

asa

positivec

ontro

land

water

(minusve

control)

TheA

mes

testrevealed

that

none

ofthep

lant

extracts

significantly

increasedthe

numbero

fHis+

revertants

with

respecttothen

egative

control

[6]

Cytoxicity

HeLaVe

roJurkatE

61

AA-

2or

CEM-SScells

Freshrhizom

esAq

ueou

s1m

gmL

Not

stated

Thee

xtractwas

nottoxicat

anyconcentrationused

inthetest

[35]

Acutetoxicity

Evaluatio

nusingbrine

shrim

pAr

temiasalin

aintersectio

nbioassay

Freshrhizom

esHexane

Not

stated

Not

stated

Theb

rines

hrim

ptest

show

edthatthec

rude

hexane

extractshave

low

toxicitywith

LC5002

[24]

Toxicity

TheH

ippo

craticteston

rats

was

used

Freshrhizom

esIsolates

from

Alepidea

amatym

bica

Hexanee

xtractive

01m

gmL

Verapamil(10m

gkg)

Allextracts

crud

eand

purifi

edsho

wed

low

toxicityrang

ingfro

mLC

5005to

5ngmLapartfrom

AA4

andAA5

that

prod

uced

slightd

iarrheao

ndays

34and5andother

extractiv

esshow

edno

toxicityatad

oseo

f20

[24]

Evidence-Based Complementary and Alternative Medicine 9

stem rhizome and root exhibited activity against Candidaalbicans extracts and more than 50 mycotic inhibitionagainst fungal cultures [6] This study does not provide adose dependent evidence of the extract and negative controlwas not used in validating the traditional use of the plantas antifungal Also all the extracts except acetone extractshowed mycotic inhibition activity against Aspergillus flavusandAspergillus niger [8]These results validate the traditionaluses of the plant as an antifungal but no dose dependentevidencewas given in this study and positive control drugwasnot used in comparison with the extract used Therefore theantifungal activity of the extract cannot be compared with anantifungal drug

53 Antiviral Louvel et al [2] investigated the screeningactivity of the aerial part and root aqueous extract of Aamatymbica against a cell-based infection assay targeting thereplication of prototypic CXCR4-tropic (NL4-3) or CCR5-tropic (NL-AD87) HIV-1 strains designed to detect inhibitorsblocking any step of the viral life cycle The active ingredientidentified in the extract does not support a direct applicationof this plant extract for treating HIV infection The anti-HIV activity of the pure compound was found to be quitemoderate Lack of negative control and a dose dependentactivity of the extract make the antiviral activity of the extractinconclusive

54 Antihelminthes Research was undertaken using nema-tode growth agar with Caenorhabditis elegans var Bristol(N2)nematodes on the ethanol extract of the fresh and storedleaves and root ofA amatymbicaOnly fresh and storedwaterextracts showed a significant Anthelminthic [33] The resultof the study did not evaluate a dose dependent inhibitionof the extract against the worms even though the controlswere compared with the extract Further investigation isthus required to validate the use of the plant in traditionalmedicine as antihelmintic

55 Anti-Inflammatory The DCM PE water and EtOHrhizome extracts were evaluated using the enzyme basedcyclooxygenase assays COX-1 and COX-2 [6] The PE andDCM extracts had high COX-1 and COX-2 activities withpercentage inhibitions above 70 Ethanol extracts showedhigher inhibition (lt40) in COX-1 than COX-2 The waterextract on the other hand has a moderate inhibition activ-ity (40ndash60) in COX-1 and lowered in COX-2 (lt20)Despite reports on the undesirable effects of higher COX-1 inhibition as a result of its damage to the gastrointestinaltract [40] report of Mulaudzi et al [6] recorded a higherCOX-1 in both DCM and PE and a lower COX-1 inhibitionin ethanol and water The result favors the use of waterand ethanol as a solvent of extraction for this plant whenusing it against inflammation However conclusion cannotbe totally drawn on this report due to lack of negativecontrol and dosage Hence further investigation is required toprovide an evidence for its traditional use against inflamma-tion

56 Antihypertensive Hexane extractive (AA1) dichloro-methane extractive and methanol extractive of the fresh rhi-zome were investigated using purified compounds on bloodpressure and heart rate of anesthetizedWistar rats Moderatebut significant decrease in systolic blood pressure (SBP) andheart rate (HT) effects after intraperitoneal application onconscious rats was reported [24]

57 Antiplasmodium Dichloromethane (DCM) DCMmethanol (MeOH) (1 1) MeOH and purified water extractfrom the whole plant were investigated on plasmodialactivity and were found to contain plant based antimalarialagents showing promising antiplasmodial activity with IC

50

values of le10 gmL [34] This is the only study showing thedose dependent antiplasmodic activity of the plant extractin relation to the positive control Validation of the use ofthe plant in vivo is necessary to conclude the antiplasmodialactivity of A amatymbica

58 Diuretic The purified compounds of the fresh rhizomeextracted in hexaneethyl acetate of A amatymbica wereinvestigated using anesthetized Wistar rats The diuretic andnatriuretic effects of the extractives were found to be similarto the effects of chlorothiazide drug [24] The result suggeststhe inhibitory effect of the extractive of A amatymbica inreabsorption of K+ and Na+ ions suggesting the diureticand natriuretic effects of the extractives Lack of testedextractive in a dose dependent manner however negates thevalidation of the plants and the extractives for use as diuretictraditionally Further investigation is required to provideevidence for its use as a diuretic

6 Toxicological Reports

Four toxicity screens were identified in the literature Eachof the four screens tested uses crude aqueous and organicsolvents hexane extracts and extractives from the crudehexane extract and none of the reports recorded toxicity atall doses testedThe reported cytotoxicity of the fresh aqueousrhizome was investigated using HeLa Vero and Jurkat E61AA-2 or CEM-SS cells The extract was shown not to betoxic at all concentrations used in the test [35] since thedosage and controls were shown in this study in comparisonwith the control The second screens use bacterial cultures(100 120583L) in an Amen test assay which were added to 100120583L ofDCM PE water and EtOH rhizome plant extracts in 500120583Lphosphate buffer and 2mLof agar containing biotin-histidine(05mM) The Ames test revealed that none of the plantextracts significantly increased the number ofHis+ revertantswith respect to the negative control [6] The third test screenutilised the Brine Shrimp Lethal Assay (BSLA) Acute toxicityof the isolates from Alepidea amatymbica was screen againstbrine shrimp Artemia salina intersection bioassay The brineshrimp test showed that the crude hexane extracts have lowtoxicity with LC

5002 ngmL while the AA6 (wedelia seco-

kaurenolide) a derivative of A amatymbica has a low toxicityof 05 ngmL [24]The fourth screenmade use of Hippocratictest on rats with the use of hexane (AA1) extract and itrsquos

10 Evidence-Based Complementary and Alternative Medicine

extractives in dichloromethane and methanol (AA1) aftersubjection to repeated flash chromatography with gradientelution (100ndash70 hexaneEtOAc) to give AA3 a crystallinemixture of ent-kaur-en-19-oic acid ent-kaura-9 (11) 16-dien-19-oic acid and trachyloban-19-oic acid AA4 16-methoxy-ent-kaur-11-en-19-oic acid AA5 11-acetoxy-ent-kaur-16-en-19-oic acid and AA6 wedelia seco-kaurenolide All extractscrude and purified showed low toxicity ranging from 05 to5 ngmL (LC

50) apart from AA4 and AA5 that produced

slight diarrhea on days 3 4 and 5 and other extractivesshowed no toxicity at a dose of 20 [24] Apart from thestudies of Treurnicht [35] and Mulaudzi et al [6] mentionedabove the other studies do not provide sufficient evidencewith respect to the safety of A amatymbica considering theabsence of dosage used and control in their assays

7 Clinical Trials

To date there appears to be no published research indicatingthat extracts ofAlepidea amatymbica have undergone humanclinical trials

8 Conclusion

The review showed that A amatymbica has a widespread usein South Africa and other SADEC countriesThe recognitionof its ethnomedicinal usage for conditions of inflammationlike rheumatism and sore throat to usage for wounds coughasthma influenza diarrhea stomach cramps abdominal dis-orders malaria and diuretic is worth mentioningThe abilityof the extract to also restrain the growth of bacteria and fungiindicated its broad spectrum antimicrobial prospective Thepharmacological reports on A amatymbica revealed thera-peutic potential in the treatment of inflammation malariaand infectious diseases like influenza cough and diarrheaThe frequently occurring chemical constituents of Alepideaamatymbica belong to the kaurene-type diterpenoids andtheir derivatives Literature search onA amatymbica revealedthe use of cell line brine shrimps and rats for the determi-nation of the toxicity in the plant More investigations arenecessary to explore themedicinal potential of the plant in themanagement of rheumatism asthma hypertension diureticand inflammation Clinical trials and product development tofully exploit the medicinal value are also required to validateits folklore use in traditional medicine There is thereforethe need to develop the existing traditional use of this plantto amplify nutraceuticals product and commence clinicalresearch to exploit the plantrsquos novel phytochemicals

Conflict of Interests

The authors declare no conflict of interests

Acknowledgments

The authors are thankful to the Govan Mbeki Research andDevelopment Centre and the National Research Fund of theUniversity of Fort Hare South Africa

References

[1] B l Burtt ldquoUmbelliferae of southern Africa an introductionand annotated checklistrdquo Edinburgh Journal of Botany vol 48pp 133ndash282 1991

[2] S Louvel N Moodley I Seibert et al ldquoIdentification ofcompounds from the plant species Alepidea amatymbica activeagainst HIVrdquo South African Journal of Botany vol 86 pp 9ndash142013

[3] G Germishuizen N L Meyer Y Steenkamp and M KeithPlants of Southern Africa An Annotated Checklist vol 41 ofSABONET Report National Botanical Institute Pretoria SouthAfrica 2006

[4] R R Klopper P Lemmer and J Nel ldquoPteridophyta Pteridaceaecheilanthes deltoidea a new locality in Gauteng South AfricardquoBothalia vol 36 no 2 pp 173ndash174 2006

[5] Z Maksimovic S Dobric N Kovacevic and Z MilovanovicldquoDiuretic activity of Maydis stigma extract in ratsrdquo Pharmazievol 59 no 12 pp 967ndash971 2004

[6] R B Mulaudzi A R Ndhlala J F Finnie and J Van StadenldquoAntimicrobial anti-inflammatory and genotoxicity activityof Alepidea amatymbica and Alepidea natalensis (Apiaceae)rdquoSouth African Journal of Botany vol 75 no 3 pp 584ndash587 2009

[7] A de Castro and B-E van Wyk ldquoDiagnostic characters andgeographic distribution of Alepidea species used in traditionalmedicinerdquo South African Journal of Botany vol 60 no 6 pp345ndash350 1994

[8] A J Afolayan and F B Lewu ldquoAntimicrobial activity ofAlepideaamatymbicardquo Pharmaceutical Biology vol 47 no 5 pp 436ndash439 2009

[9] C Njume A A Jide and R N Ndip ldquoAqueous and organicsolvent-extracts of selected South African medicinal plantspossess antimicrobial activity against drug-resistant strainsof Helicobacter pylori inhibitory and bactericidal potentialrdquoInternational Journal of Molecular Sciences vol 12 no 9 pp5652ndash5665 2011

[10] J M Watt and M G Breyer-Brandwijik The Medicinal andPoisonous Plants of Southern and Eastern Africa E and SLivingstone London UK 2nd edition 1962

[11] B E van Wyk A de Castro P M Tilney P J D Winter andA R Magee ldquoA new species of Alepidea (Apiaceae subfamSaniculoideae)rdquo South African Journal of Botany vol 74 no 4pp 740ndash745 2008

[12] J T Mukinda and P F K Eagles ldquoThe South African Pharma-copoeia Monograph Projectrdquo Developed by South African Tra-ditional Medicines Research Group (SATMERG) and Schoolof Pharmacy University of the Western Cape (Unpublished)2010

[13] A Mapaura and J R Timberlake ldquoSouthern African plantred data listsrdquo Southern African Botanical Diversity Network(SABONET) Report 14 SABONET Pretoria South Africa

[14] A Maroyi ldquoEthnobotanical study of two threatened medicinalplants in Zimbabwerdquo International Journal of Biodiversity Sci-ence and Management vol 4 no 3 pp 148ndash153 2008

[15] S Talukdar ldquoLesothordquo in Southern African Plant Red Data ListsJ Golding Ed Southern African Botanical Diversity Network(SABONET) Report Number 14 pp 21ndash30 SABONET Preto-ria South Africa 2002

[16] R Scott-Shaw ldquoRare and threatened plants of KwaZulu-Nataland neighbouring regionsrdquo in A Plant Red Data Book p182 KwaZulu-Natal Nature Conservation Service Pietermar-itzburg South Africa 1999

Evidence-Based Complementary and Alternative Medicine 11

[17] The Plant List 2012 httpwwwtheplantlistorg[18] S Nonjinge and B B Tarr Natal National Botanical Garden

2013 httpwwwplantzafricacomplantabalipedeamathtm[19] M Gelfand S Mavi R B Drummond and B Ndemera The

Traditional Medical Practitioner in Zimbabwe Mambo PressGweru Zimbabwe 1985

[20] B E VanWyk and N Gericke rsquoPeoplersquos PlantsmdashA Guide toUseful Plants of South Africa Briza Publication Pretoria SouthAfrica 2000

[21] A Hutchings A H Scott G Lewis and A CunninghamZulu Medicinal Plants An Inventory University of Natal PressScottsville South Africa 1996

[22] B E van Wyk B van Oudtshoorn and N Gericke MedicinalPlants of South Africa Briza Publications Pretoria SouthAfrica 1997

[23] J A Guillarmod Flora of Lesotho J Cramer Lehre Germany1971

[24] L I Somova F O Shode K Moodley and Y GovenderldquoCardiovascular and diuretic activity of kaurene derivativesof Xylopia aethiopica and Alepidea amatymbicardquo Journal ofEthnopharmacology vol 77 no 2-3 pp 165ndash174 2001

[25] J Pujol NaturAfrica The Herbalists Handbook Jean PujolNatural Healers Foundation Durban South Africa 1990

[26] A Hutchings and J van Staden ldquoPlants used for stress-relatedailments in traditional Zulu Xhosa and Sotho medicine Part 1plants used for headachesrdquo Journal of Ethnopharmacology vol43 no 2 pp 89ndash124 1994

[27] A Hutchings ldquorsquoObservations on plant usage in Xhosa and Zulumedicinerdquo Bothalia vol 19 pp 225ndash235 1989

[28] J F Sobiecki ldquoA preliminary inventory of plants used forpsychoactive purposes in southern African healing traditionsrdquoTransactions of the Royal Society of SouthAfrica vol 57 pp 1ndash242002

[29] S O Bandeira F Gaspar and F P Pagula ldquoAfrican ethnobotanyand healthcare emphasis on Mozambiquerdquo PharmaceuticalBiology vol 39 pp 70ndash73 2001

[30] A Rustaiyan and A S Sadjadi ldquoKaurene derivatives fromAlepidea amatynsiardquo Phytochemistry vol 26 no 7 pp 2106ndash2107 1987

[31] C W Holzapfel B E van Wyk A de Castro W Marais andM Herbst ldquoA chemotaxonomic survey of kaurene derivativesin the genus Alepidea (Apiaceae)rdquo Biochemical Systematics andEcology vol 23 no 7-8 pp 799ndash803 1995

[32] D K Olivier B van Wyk and F R van Heerden ldquoThechemotaxonomic and medicinal significance of phenolic acidsin Arctopus and Alepidea (Apiaceae subfamily Saniculoideae)rdquoBiochemical Systematics and Ecology vol 36 no 9 pp 724ndash7292008

[33] G I Stafford A K Jager and J van Staden ldquoEffect ofstorage on the chemical composition and biological activityof several popular South African medicinal plantsrdquo Journal ofEthnopharmacology vol 97 no 1 pp 107ndash115 2005

[34] C Clarkson V JMaharaj N R Crouch et al ldquoIn vitro antiplas-modial activity of medicinal plants native to or naturalised inSouth Africardquo Journal of Ethnopharmacology vol 92 no 2-3pp 177ndash191 2004

[35] F T TreurnichtAn evaluation of the toxic and potential antiviraleffects of some plants used by South Africans for medicinalpurposes [MS thesis] University of Stellenbosch StellenboschSouth Africa 1997

[36] A Hutchings Zulu Medicinal Plants Natal University PressPietermaritzburg South Africa 1996

[37] C I Wright L van-Buren C I Kroner and M M GKoning ldquoHerbalmedicines as diuretics a reviewof the scientificevidencerdquo Journal of Ethnopharmacology vol 114 no 1 pp 1ndash312007

[38] F O Shode and B C Rogers ldquoThe chemistry of ApiaceaeIsolation and characterisation of diterpenoids and other ter-penoids from Alepidea amatymbicardquo in Proceedings of the 7thInternational Chemistry Conference in Africa Durban SouthAfrica 1998

[39] C W Fennell M E Light S G Sparg G I Stafford and JVan Staden ldquoAssessingAfricanmedicinal plants for efficacy andsafety agricultural and storage practicesrdquo Journal of Ethnophar-macology vol 95 no 2-3 pp 113ndash121 2004

[40] D Luseba E E Elgorashi D T Ntloedibe and J Van StadenldquoAntibacterial anti-inflammatory and mutagenic effects ofsome medicinal plants used in South Africa for the treatmentof wounds and retained placenta in livestockrdquo South AfricanJournal of Botany vol 73 no 3 pp 378ndash383 2007

Submit your manuscripts athttpwwwhindawicom

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Disease Markers

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OncologyJournal of

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Oxidative Medicine and Cellular Longevity

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The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

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ObesityJournal of

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Research and TreatmentAIDS

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Gastroenterology Research and Practice

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Parkinsonrsquos Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom

Page 3: Review Article Alepidea amatymbica Eckl. & Zeyh.: A Review ...downloads.hindawi.com/journals/ecam/2014/284517.pdf · A Review of Its Traditional Uses, Phytochemistry, Pharmacology,

Evidence-Based Complementary and Alternative Medicine 3

Table 1 Traditional uses of Alepidea amatymbica Eckl amp Zeyh

Category of use Description of traditional dosage References

Cultural and dietary

The dry rhizome and roots are smoked or powdered and taken as a snuff by divinersand healers to assist in divination and communication with ancestors [20ndash22]

Smoking the roots reportedly results in mild sedation and vivid dreams [22]The dry rhizome and roots are used as a lotion to wash the divining bones [23]

Antihypertensive Fresh rhizomes [22 24]Nervousness Dry rhizome and roots [25]Antimicrobial Leaf stem rhizome and root [8 22]Diuretic effects Fresh rhizome [22 24]

Respiratory Rhizomes and roots are used for colds coughs and influenza and respiratoryailments [7 10 21 22 25 26]

Inflammatory conditions Rhizomes and roots are used for rheumatism and wounds [10 21 22]Gastrointestinal Rhizomes and roots are used for stomach [10 21 22]Purgative Rhizomes for the treatment of abdominal disorders [7 27]Mild sedation and vivid dreams Smoking the roots [20 28]Antimalaria Rhizome [29]Astringent Fresh rhizome is applied externally [7 12]

the recommended adult dose is one tablespoonful of rawor cooked rhizome and root for children one to two tea-spoonfuls according to age is sufficient Fresh or cookedrhizome and roots are chewed or sucked and fresh rhizomeis also applied externally as a styptic [7 12] The dry rhizomeand roots are smoked or powdered and taken as a snuff byunspecified diviners and healers in South Africa to assistin divination and communication with the ancestors [20]Smoke from burning of the dry plant material is inhaled anda root infusion taken orally or administered per rectum asan enema [25] Smoking the roots results in mild sedationand vivid dreams and a decoction made of the dried productis taken or fresh rhizomes are chewed It is also burnedand inhaled or administered as snuff [7 12] Zulu herbalists(Izinyanga) prescribe the plant to help prevent nervousnessin South Africa [25]

32 Contradictions Alepidea amatymbica rhizome isbelieved to be used as a diuretic by Somova et al [24] but theplant was reported by Wright et al [37] to have no diureticeffect in an overview of plants with putative diuretic effects

4 Chemical Constituents

Some of the phytochemicals isolated and characterized todate fromAlepidea amatymbica are showed in Figure 2Theseinclude kaurene-type diterpenoids and their derivatives likeent-9 (11)-dehydro-16-kauren-19-oic acid ent-16-kauren-19-oic acid wedelia seco-kaurenolide and 313-acetoxy whichis believed to constitute up to 118 of rhizome and rootdry mass [20] The activity of the medicine can most likelybe attributed to the diterpenoids it contains although theyhave not been tested individually [20] Several diterpenoidkaurene derivatives have been isolated from the rhizomesand roots of A amatymbica [30 31 38] Lipophilic extracts

of the powdered dried rhizomes of A amatymbica collectedin different localities also confirmed the presence of ent-9(11)-dehydro-16-kauren-19-oic acid (la) ent-16-kauren-19-oicacid (2a) wedelia seco-kaurenolide (3) and (4) and the 313-acetoxy derivative of 3 previously reported as constituentsof the roots and aerial parts of A amatymbica [30] Theextracts contained additional kaurene derivatives not pre-viously reported A comparative study of dichloromethaneextracts of the roots of several Alepidea species showed thepresence of kaurene derivatives in every caseThedistributionof all the major compounds found in Alepidea amatymbica issummarized in Table 2The highly resinous rhizomes containkaurene-type diterpenoids [30 31]

5 Pharmacological Reports

Different pharmacological areas were revealed in the litera-ture search on A amatymbica investigation These includeanti-inflammatory antibacterial antifungal antihelminticantimalarial antihypertensive and diuretic activities Thesummarized detail of the pharmacological studies on Aamatymbica was showed in Table 3 However there is dearthof information in literature on the pharmacological effectsof the active principles of A amatymbica Hutchings [27]reported the performance of screening tests on the basis ofpersonal communication with a pharmaceutical companyindicating the antimicrobial antihypertensive and diureticactivity [24]

51 Antimicrobial Activity Crude dichloromethane petrole-umether ethanol and aqueous rhizome extracts demonstratestrong antibacterial activity against both gram-negative andgram-positive bacteria used However the crude PE andDCM rhizome extracts exhibited the best MIC (039mgmL)against B subtilis and the rest of the extracts were shown to

4 Evidence-Based Complementary and Alternative Medicine

H3C CH2

CH2

O OH COOHOAc

Me

Me

R

R

R

SSS H

HHO2C

Ent-kaur-16-en-19-oic acid

16120572-Methoxy-ent-kaur-en-19-oic acid

15120573-Acetoxy-(mdash)-kaur-16-en-19-oic acid

Sources (ChemSpider sigma-Aldrich and Google)

Figure 2 Chemical structures of kaurene-type diterpenoids in Alepidea amatymbica

Table 2 Chemical groups part of the plant studied and isolated compounds isolated from Alepidea amatymbica Eckl amp Zeyh

Phytochemicals Compound Plant part Reference

Terpenes(kaurene-type diterpenoids)

ent-9 (11)-dehydro-16-kauren-19-oic acid Rhizomes and roots [30 31]ent-16-kauren-19-oic acid Dried rhizomes [30]wedelia seco-kaurenolide Dried rhizomes [12 30]313-acetoxy Dried rhizomes [30]

Phenolic acid Phenolic acid Rhizome [32]Rosmarinic acid 31015840-O-120573-d-Glucopyranosyl rosmarinic acid Rhizome [2]

have low activity (MIC value gt 1mgmL) [6]The dosage andMIC of the plant extract used in this study showed activityagainst the bacterial tested when compared to the controlThis suggests that the result favors its usage in traditionalmedicine for the treatment of bacterial infections

In a related work the crude extracts of the leaf stemrhizome and root of A amatymbica exhibit a range of anti-microbial properties against the following bacteria Bacilluscereus Staphylococcus epidermidis Staphylococcus aureusMicrococcus kristinae Streptococcus pyogenes Escherichiacoli Salmonella poona Serratia marcescens Pseudomonasaeruginosa and Klebsiella pneumoniaeThe acetone rhizomeextract showed better activity than others especially on Saureus and B cereus and moderate activity was recordedagainst the gram-positive bacteria tested with the exceptionofMicrococcus kristinae [8] Although the inhibitionwas highin all the parts of the plant tested the acetone and methanolstem extract showed a weak activity against Streptococcuspyogenes This result supports the use of A amatymbicain treating bacterial diseases associated with respiratorytract urinary tract and gastrointestinal tract infections Dueto lack of positive control in this work it is difficult to

draw conclusions on the study Thus further investigation isrequired to justify its traditional usage as antibacterial

The fresh and 90-day dried crude extract of the leafand rhizome extract of A amatymbica prepared in waterethanol and hexane were used in this study [9] The extractsdemonstrated anti-H pylori activity with zone of inhibitionrange of 0ndash38mm and MIC

50range of 006ndash50mgmL

respectively The antimicrobial activity was comparable withthe control antibiotics HoweverA amatymbica extracts gavea susceptibility of less than 50

The antibacterial activity also increased with storage orageing of plant material [33] Antibacterial activity is stablein dry specimens and as such may account for the factthat activity is unaffected by storage in certain instances[39] Therefore the result favors the use of the plant as anantibacterial considering the activity of the extract and thecontrol even though the dosage was not stated Hence morework is needed in the validation of the plant extract for thetreatment of bacterial infections

52 Antifungal Activity Antifungal activities of A amatym-bica have been reported [6 8] The crude extracts of the leaf

Evidence-Based Complementary and Alternative Medicine 5

Table3Ph

armacologicalinvestigationof

Alepidea

amatym

bica

Ecklamp

Zeyh

Activ

ityteste

dMod

elused

Plantp

art

usedte

sted

material

Extracttype

Dosage

Con

trol

Results

Reference

Antibacteria

l

Nutrie

ntagar

medium

was

mixed

with

extractand

bacteriasuspensio

nSpeciesstrainsB

acillus

subtilisA

TCC6051

and

Staphylococcus

aureus

ATCC

1260

0and

Escherich

iacoliAT

CC117

75andKlebsiella

pneumoniae

ATCC

13883

Rhizom

eDCM

PE

waterand

EtOHrhizom

eextracts

1mgm

LWater

andbacteriafre

ebroth(minusve)01m

gmL

neom

ycin

(+ve)

TheP

EandDCM

extracts

ofther

hizomes

exhibited

theb

estactivity

(MIC

values

of039

mgmL)

againstB

subtilis

Ther

est

ofthee

xtractssho

wedlow

activ

ity(M

ICvalues

gt1m

gmL)

[6]

Antibacteria

l

Agard

ilutio

nmetho

dswith

thefollowingorganism

sBa

cilluscereus

Staphylococcus

epidermidis

Staphylococcus

aureus

Micrococcusk

ristin

ae

Streptococcusp

yogenes

Escherich

iacoliSalm

onella

poonaSerratiamarcescens

Pseudomonas

aeruginosa

andKlebsiella

pneumoniae

Crud

eextractso

ftheleafste

m

rhizom

eandroot

Aceton

eand

methano

l1ndash10mgmL

Plates

containing

1aceton

eand

methano

lin

agar

Thea

cetone

rhizom

eextractsho

wed

bette

ractiv

itythan

others

especiallyon

Saureus

and

Bcereus

mod

eratea

ctivity

thatwas

recorded

againstthe

gram

-positive

bacteria

teste

dwith

thee

xceptio

nof

Micrococcusk

ristin

ae

[8]

Antim

icrobial

Microdilutio

nmetho

don

Mueller-Hintonbroth

SpeciesB

acillus

subtilis

Staphylococcus

aureus

Escherich

iacoliand

Klebsiella

pneumoniae

Rhizom

eand

leaf

(fresh90

days

old

andon

e-year-o

ldmaterial)were

assayed

Waterethanoland

hexane

extracts

125625313156

078039

020and

01m

gmL

Extract-frees

olutionand

ethano

lwereu

sedas

ablankcontroland

neom

ycin

(+ve)

Thew

ater

extractsof

plants

teste

dfora

ntibacteria

lactiv

ityshow

edno

activ

ity

whereas

thee

thanol

extractsgenerally

show

edan

increase

inactiv

ityTh

eantib

acteria

lactivity

increase

with

storage

orageing

ofplantm

aterial

[33]

Antim

icrobial

Agarw

elldiffu

sionmetho

dusingHpyloriino

cula

prepared

atMcFarland

rsquosturbidity

standard

2was

plated

onto

BHIa

gar

supp

lementedwith

5ho

rseb

lood

andSkirr

owrsquos

supp

lement

Rootsrhizom

esEthylacetateacetone

ethano

lmethano

landwater

100m

gmL

Clarith

romycin

and10

DMSO

wereu

sedas

positivea

ndnegativ

econtrols

respectiv

ely

Thep

lantsd

emon

strated

anti-Hpyloriactivity

with

zone

diam

eterso

finhibitio

nbetween0and

38mm

and50minim

uminhibitory

concentration

(MIC50)v

aluesranging

from

006

to50m

gmL

[9]

6 Evidence-Based Complementary and Alternative MedicineTa

ble3Con

tinued

Activ

ityteste

dMod

elused

Plantp

art

usedte

sted

material

Extracttype

Dosage

Con

trol

Results

Reference

Antim

icrobial

Agarw

elldiffu

sionmetho

dAlepidea

amatym

bica

were

investigated

against30

clinicalstrains

ofHpylori

Rootsrhizom

esEthylacetateacetone

ethano

lmethano

landwater

0002ndash50m

gmL

Referencec

ontro

lstrain

(NCT

C116

38)

Metronidazoleand

amoxicillin

wereincluded

aspo

sitivec

ontro

lantib

iotic

s

Methano

lwas

quantitatively

theb

est

solventfor

allthe

plants

whileethylacetatehadthe

lowestyieldsA

amatym

bica

gave

percentage

susceptib

ilitie

sof

lessthan

50

[9]

Antifu

ngal

Agard

ilutio

nmetho

dswith

thefollowingorganism

sAspergillus

flavus

Aspergillus

nigerand

Penicilliu

mnotatum

cultu

resw

erem

aintained

onPo

tato

Dextro

seagar

Crud

eextractso

ftheleafste

m

rhizom

eandroot

Aceton

eand

methano

l

Radialpatte

rnof

streakingof

organism

swas

used

Plates

containing

onlyPD

Aor

PDAwith

ther

espective

solvent

Diameter

ofthefun

gal

grow

thwas

measuredand

expressedas

percentage

grow

thinhibitio

nAllthe

extractsshow

edmorethan

50mycoticinhibitio

nwith

activ

ityrang

ingfro

m5139

to

8111at

5mgmLwith

ther

hizome

[8]

Antifu

ngal

Thea

ntifu

ngalactiv

ityof

thee

xtractsw

asevaluated

againstC

andida

albicans

(ATC

C10231)andfung

alcultu

rewas

prepared

inYeastM

alt(YM

)

Rhizom

eDCM

PE

waterand

EtOHrhizom

eextracts

01ndash50m

gmL

Water

andbacteriafre

ebroth(minusve)01m

gmL

neom

ycin

(+ve)

Allthee

xtractssho

wed

activ

ityagainstC

andida

albicans

[6]

Anti-infl

ammatory

Usin

gthee

nzym

ebased

cyclo

oxygenasea

ssays

COX-

1and

COX-

2Rh

izom

eDCM

PE

waterand

EtOHrhizom

eextracts

1mgmL

Water

andbacteriafre

ebroth(minusve)01m

gmL

neom

ycin

(+ve)

TheP

EandDCM

extracts

hadhigh

COX-

1activity

with

percentage

inhibitio

nsabove7

0E

thanol

extractshadinhibitio

nless

than

40

[6]

Antihypertensive

Purifi

edcompo

unds

onbloo

dpressure

andheart

rateof

anesthetized

Wistar

rats

Freshrhizom

es

Hexanee

xtractive

(AA1)

dichloromethane

extractiv

eand

methano

lextractive

ipinjectio

nof

sodium

thiopenton

e(40m

gkg

body

weight)

Chlorothiazide

Inadditio

nto

the

cardiovascular

effects

distinctdiureticand

natriuretic

effectswere

foun

d

[24]

Antiplasm

odium

Plasmodium

falciparum

strainD10

usingthe

parasitelactate

dehydrogenase(pL

DH)

assay

Who

leplant

Dichlorom

ethane

(DCM

)DCM

methano

l(M

eOH)(11)

MeO

Hand

purifi

edwater

100ndash

02120583

gmL)

Chloroqu

ined

ipho

sphate

served

asthep

ositive

control

Detectp

lant-based

antim

alarialagents

show

ingprom

ising

antip

lasm

odialactivity

with

IC50

values

ofle10gmL

[34]

Diuretic

TheL

ipschitztestwas

used

todeterm

inethe

Diuretic

andsaluretic

activ

ityin

rats

Freshrhizom

eHexaneethylacetate

extract

Thetestcom

poun

dwas

appliedorallyata

dose

of50

mgkg

Urea(

1gkgb

w)

Hydrochlorothiazide

(25m

gkg

bw)

Thed

iuretic

andnatriuretic

effectsof

thee

xtractives

werefou

ndto

besim

ilarto

thee

ffectso

fchlorothiazide

[24]

Evidence-Based Complementary and Alternative Medicine 7

Table3Con

tinued

Activ

ityteste

dMod

elused

Plantp

art

usedte

sted

material

Extracttype

Dosage

Con

trol

Results

Reference

Cardiovascular

Purifi

edcompo

unds

onbloo

dpressure

andheart

rateof

anesthetized

Wistar

rats

Purifi

edcompo

undfro

mfre

shrhizom

e

Hexanee

xtract

(AA1)

dichloromethaneand

methano

lportio

nof

AA1weres

ubjected

torepeated

flash

chromatograph

ywith

gradient

elutio

n(100ndash70

hexaneEtO

Ac)to

give

AA3a

crystalline

mixture

ofent-k

aur-en-19-oic

acident-kaura-9

(11)

16-dien-19-oicacid

and

trachyloban-19-oic

acidA

A4

16-m

etho

xy-ent-kaur-

11-en-19-oica

cid

AA511-a

cetoxy-ent-

kaur-16-en-19-oic

acidand

AA6

wedelia

seco-kaureno

lide

20mgkg

bw

intraperito

neally

Ethylene

glycol

Mod

eratebu

tsignificant

decreasin

gsysto

licbloo

dpressure

(SBP

)and

heart

rate(H

T)effectsaft

erintraperito

nealapplication

onconsciou

srats

[24]

Anti-H

IV

Extractsandtherein

subfractions

ofA

amatym

bica

werea

ssessed

inac

ellbased

assay

targetingther

eplicationof

prototypicCX

CR4-tro

pic

(NL4

-3)o

rCCR

5-tro

pic

(NL-AD87)H

IV-1str

ains

Aeria

lpartsand

roots

Aqueou

s500120583

Lof

samplea

taconcentrationof

25mgmL

Standard

retro

viral

inhibitor

Thea

ctiveing

redient

identifi

edin

thea

queous

extractd

oesn

otsupp

orta

directapplicationof

this

plantextractfortreating

HIV

infection

The

anti-HIV

activ

ityof

the

pure

compo

undwas

foun

dto

bequ

itemod

erate

[212]

Antihelminthes

Nem

atod

egrowth

agar

with

Caenorhabditiseleg

ans

varBristol(N

2)nematod

es

Freshandsto

red

leaves

androot

Ethano

l1m

gmL

Levamiso

le(+Ve

)and

nematod

eincub

ated

with

water

(minusVe

)

Onlyfre

shandsto

redwater

extractsshow

eda

significantantihelminthes

[33]

8 Evidence-Based Complementary and Alternative Medicine

Table3Con

tinued

Activ

ityteste

dMod

elused

Plantp

art

usedte

sted

material

Extracttype

Dosage

Con

trol

Results

Reference

Toxicity

Theb

acteria

lcultures

(100120583L)

werea

dded

to100120583

Lof

plantextractin

500120583

Lph

osph

ateb

uffer

and2m

Lof

agar

containing

biotin-histidine(05m

M)

Rhizom

eDCM

PE

waterand

EtOHrhizom

eextracts

50500and

5000120583gmL

4-Nitroq

uino

line-N-oxide

(4NQO)w

asused

asa

positivec

ontro

land

water

(minusve

control)

TheA

mes

testrevealed

that

none

ofthep

lant

extracts

significantly

increasedthe

numbero

fHis+

revertants

with

respecttothen

egative

control

[6]

Cytoxicity

HeLaVe

roJurkatE

61

AA-

2or

CEM-SScells

Freshrhizom

esAq

ueou

s1m

gmL

Not

stated

Thee

xtractwas

nottoxicat

anyconcentrationused

inthetest

[35]

Acutetoxicity

Evaluatio

nusingbrine

shrim

pAr

temiasalin

aintersectio

nbioassay

Freshrhizom

esHexane

Not

stated

Not

stated

Theb

rines

hrim

ptest

show

edthatthec

rude

hexane

extractshave

low

toxicitywith

LC5002

[24]

Toxicity

TheH

ippo

craticteston

rats

was

used

Freshrhizom

esIsolates

from

Alepidea

amatym

bica

Hexanee

xtractive

01m

gmL

Verapamil(10m

gkg)

Allextracts

crud

eand

purifi

edsho

wed

low

toxicityrang

ingfro

mLC

5005to

5ngmLapartfrom

AA4

andAA5

that

prod

uced

slightd

iarrheao

ndays

34and5andother

extractiv

esshow

edno

toxicityatad

oseo

f20

[24]

Evidence-Based Complementary and Alternative Medicine 9

stem rhizome and root exhibited activity against Candidaalbicans extracts and more than 50 mycotic inhibitionagainst fungal cultures [6] This study does not provide adose dependent evidence of the extract and negative controlwas not used in validating the traditional use of the plantas antifungal Also all the extracts except acetone extractshowed mycotic inhibition activity against Aspergillus flavusandAspergillus niger [8]These results validate the traditionaluses of the plant as an antifungal but no dose dependentevidencewas given in this study and positive control drugwasnot used in comparison with the extract used Therefore theantifungal activity of the extract cannot be compared with anantifungal drug

53 Antiviral Louvel et al [2] investigated the screeningactivity of the aerial part and root aqueous extract of Aamatymbica against a cell-based infection assay targeting thereplication of prototypic CXCR4-tropic (NL4-3) or CCR5-tropic (NL-AD87) HIV-1 strains designed to detect inhibitorsblocking any step of the viral life cycle The active ingredientidentified in the extract does not support a direct applicationof this plant extract for treating HIV infection The anti-HIV activity of the pure compound was found to be quitemoderate Lack of negative control and a dose dependentactivity of the extract make the antiviral activity of the extractinconclusive

54 Antihelminthes Research was undertaken using nema-tode growth agar with Caenorhabditis elegans var Bristol(N2)nematodes on the ethanol extract of the fresh and storedleaves and root ofA amatymbicaOnly fresh and storedwaterextracts showed a significant Anthelminthic [33] The resultof the study did not evaluate a dose dependent inhibitionof the extract against the worms even though the controlswere compared with the extract Further investigation isthus required to validate the use of the plant in traditionalmedicine as antihelmintic

55 Anti-Inflammatory The DCM PE water and EtOHrhizome extracts were evaluated using the enzyme basedcyclooxygenase assays COX-1 and COX-2 [6] The PE andDCM extracts had high COX-1 and COX-2 activities withpercentage inhibitions above 70 Ethanol extracts showedhigher inhibition (lt40) in COX-1 than COX-2 The waterextract on the other hand has a moderate inhibition activ-ity (40ndash60) in COX-1 and lowered in COX-2 (lt20)Despite reports on the undesirable effects of higher COX-1 inhibition as a result of its damage to the gastrointestinaltract [40] report of Mulaudzi et al [6] recorded a higherCOX-1 in both DCM and PE and a lower COX-1 inhibitionin ethanol and water The result favors the use of waterand ethanol as a solvent of extraction for this plant whenusing it against inflammation However conclusion cannotbe totally drawn on this report due to lack of negativecontrol and dosage Hence further investigation is required toprovide an evidence for its traditional use against inflamma-tion

56 Antihypertensive Hexane extractive (AA1) dichloro-methane extractive and methanol extractive of the fresh rhi-zome were investigated using purified compounds on bloodpressure and heart rate of anesthetizedWistar rats Moderatebut significant decrease in systolic blood pressure (SBP) andheart rate (HT) effects after intraperitoneal application onconscious rats was reported [24]

57 Antiplasmodium Dichloromethane (DCM) DCMmethanol (MeOH) (1 1) MeOH and purified water extractfrom the whole plant were investigated on plasmodialactivity and were found to contain plant based antimalarialagents showing promising antiplasmodial activity with IC

50

values of le10 gmL [34] This is the only study showing thedose dependent antiplasmodic activity of the plant extractin relation to the positive control Validation of the use ofthe plant in vivo is necessary to conclude the antiplasmodialactivity of A amatymbica

58 Diuretic The purified compounds of the fresh rhizomeextracted in hexaneethyl acetate of A amatymbica wereinvestigated using anesthetized Wistar rats The diuretic andnatriuretic effects of the extractives were found to be similarto the effects of chlorothiazide drug [24] The result suggeststhe inhibitory effect of the extractive of A amatymbica inreabsorption of K+ and Na+ ions suggesting the diureticand natriuretic effects of the extractives Lack of testedextractive in a dose dependent manner however negates thevalidation of the plants and the extractives for use as diuretictraditionally Further investigation is required to provideevidence for its use as a diuretic

6 Toxicological Reports

Four toxicity screens were identified in the literature Eachof the four screens tested uses crude aqueous and organicsolvents hexane extracts and extractives from the crudehexane extract and none of the reports recorded toxicity atall doses testedThe reported cytotoxicity of the fresh aqueousrhizome was investigated using HeLa Vero and Jurkat E61AA-2 or CEM-SS cells The extract was shown not to betoxic at all concentrations used in the test [35] since thedosage and controls were shown in this study in comparisonwith the control The second screens use bacterial cultures(100 120583L) in an Amen test assay which were added to 100120583L ofDCM PE water and EtOH rhizome plant extracts in 500120583Lphosphate buffer and 2mLof agar containing biotin-histidine(05mM) The Ames test revealed that none of the plantextracts significantly increased the number ofHis+ revertantswith respect to the negative control [6] The third test screenutilised the Brine Shrimp Lethal Assay (BSLA) Acute toxicityof the isolates from Alepidea amatymbica was screen againstbrine shrimp Artemia salina intersection bioassay The brineshrimp test showed that the crude hexane extracts have lowtoxicity with LC

5002 ngmL while the AA6 (wedelia seco-

kaurenolide) a derivative of A amatymbica has a low toxicityof 05 ngmL [24]The fourth screenmade use of Hippocratictest on rats with the use of hexane (AA1) extract and itrsquos

10 Evidence-Based Complementary and Alternative Medicine

extractives in dichloromethane and methanol (AA1) aftersubjection to repeated flash chromatography with gradientelution (100ndash70 hexaneEtOAc) to give AA3 a crystallinemixture of ent-kaur-en-19-oic acid ent-kaura-9 (11) 16-dien-19-oic acid and trachyloban-19-oic acid AA4 16-methoxy-ent-kaur-11-en-19-oic acid AA5 11-acetoxy-ent-kaur-16-en-19-oic acid and AA6 wedelia seco-kaurenolide All extractscrude and purified showed low toxicity ranging from 05 to5 ngmL (LC

50) apart from AA4 and AA5 that produced

slight diarrhea on days 3 4 and 5 and other extractivesshowed no toxicity at a dose of 20 [24] Apart from thestudies of Treurnicht [35] and Mulaudzi et al [6] mentionedabove the other studies do not provide sufficient evidencewith respect to the safety of A amatymbica considering theabsence of dosage used and control in their assays

7 Clinical Trials

To date there appears to be no published research indicatingthat extracts ofAlepidea amatymbica have undergone humanclinical trials

8 Conclusion

The review showed that A amatymbica has a widespread usein South Africa and other SADEC countriesThe recognitionof its ethnomedicinal usage for conditions of inflammationlike rheumatism and sore throat to usage for wounds coughasthma influenza diarrhea stomach cramps abdominal dis-orders malaria and diuretic is worth mentioningThe abilityof the extract to also restrain the growth of bacteria and fungiindicated its broad spectrum antimicrobial prospective Thepharmacological reports on A amatymbica revealed thera-peutic potential in the treatment of inflammation malariaand infectious diseases like influenza cough and diarrheaThe frequently occurring chemical constituents of Alepideaamatymbica belong to the kaurene-type diterpenoids andtheir derivatives Literature search onA amatymbica revealedthe use of cell line brine shrimps and rats for the determi-nation of the toxicity in the plant More investigations arenecessary to explore themedicinal potential of the plant in themanagement of rheumatism asthma hypertension diureticand inflammation Clinical trials and product development tofully exploit the medicinal value are also required to validateits folklore use in traditional medicine There is thereforethe need to develop the existing traditional use of this plantto amplify nutraceuticals product and commence clinicalresearch to exploit the plantrsquos novel phytochemicals

Conflict of Interests

The authors declare no conflict of interests

Acknowledgments

The authors are thankful to the Govan Mbeki Research andDevelopment Centre and the National Research Fund of theUniversity of Fort Hare South Africa

References

[1] B l Burtt ldquoUmbelliferae of southern Africa an introductionand annotated checklistrdquo Edinburgh Journal of Botany vol 48pp 133ndash282 1991

[2] S Louvel N Moodley I Seibert et al ldquoIdentification ofcompounds from the plant species Alepidea amatymbica activeagainst HIVrdquo South African Journal of Botany vol 86 pp 9ndash142013

[3] G Germishuizen N L Meyer Y Steenkamp and M KeithPlants of Southern Africa An Annotated Checklist vol 41 ofSABONET Report National Botanical Institute Pretoria SouthAfrica 2006

[4] R R Klopper P Lemmer and J Nel ldquoPteridophyta Pteridaceaecheilanthes deltoidea a new locality in Gauteng South AfricardquoBothalia vol 36 no 2 pp 173ndash174 2006

[5] Z Maksimovic S Dobric N Kovacevic and Z MilovanovicldquoDiuretic activity of Maydis stigma extract in ratsrdquo Pharmazievol 59 no 12 pp 967ndash971 2004

[6] R B Mulaudzi A R Ndhlala J F Finnie and J Van StadenldquoAntimicrobial anti-inflammatory and genotoxicity activityof Alepidea amatymbica and Alepidea natalensis (Apiaceae)rdquoSouth African Journal of Botany vol 75 no 3 pp 584ndash587 2009

[7] A de Castro and B-E van Wyk ldquoDiagnostic characters andgeographic distribution of Alepidea species used in traditionalmedicinerdquo South African Journal of Botany vol 60 no 6 pp345ndash350 1994

[8] A J Afolayan and F B Lewu ldquoAntimicrobial activity ofAlepideaamatymbicardquo Pharmaceutical Biology vol 47 no 5 pp 436ndash439 2009

[9] C Njume A A Jide and R N Ndip ldquoAqueous and organicsolvent-extracts of selected South African medicinal plantspossess antimicrobial activity against drug-resistant strainsof Helicobacter pylori inhibitory and bactericidal potentialrdquoInternational Journal of Molecular Sciences vol 12 no 9 pp5652ndash5665 2011

[10] J M Watt and M G Breyer-Brandwijik The Medicinal andPoisonous Plants of Southern and Eastern Africa E and SLivingstone London UK 2nd edition 1962

[11] B E van Wyk A de Castro P M Tilney P J D Winter andA R Magee ldquoA new species of Alepidea (Apiaceae subfamSaniculoideae)rdquo South African Journal of Botany vol 74 no 4pp 740ndash745 2008

[12] J T Mukinda and P F K Eagles ldquoThe South African Pharma-copoeia Monograph Projectrdquo Developed by South African Tra-ditional Medicines Research Group (SATMERG) and Schoolof Pharmacy University of the Western Cape (Unpublished)2010

[13] A Mapaura and J R Timberlake ldquoSouthern African plantred data listsrdquo Southern African Botanical Diversity Network(SABONET) Report 14 SABONET Pretoria South Africa

[14] A Maroyi ldquoEthnobotanical study of two threatened medicinalplants in Zimbabwerdquo International Journal of Biodiversity Sci-ence and Management vol 4 no 3 pp 148ndash153 2008

[15] S Talukdar ldquoLesothordquo in Southern African Plant Red Data ListsJ Golding Ed Southern African Botanical Diversity Network(SABONET) Report Number 14 pp 21ndash30 SABONET Preto-ria South Africa 2002

[16] R Scott-Shaw ldquoRare and threatened plants of KwaZulu-Nataland neighbouring regionsrdquo in A Plant Red Data Book p182 KwaZulu-Natal Nature Conservation Service Pietermar-itzburg South Africa 1999

Evidence-Based Complementary and Alternative Medicine 11

[17] The Plant List 2012 httpwwwtheplantlistorg[18] S Nonjinge and B B Tarr Natal National Botanical Garden

2013 httpwwwplantzafricacomplantabalipedeamathtm[19] M Gelfand S Mavi R B Drummond and B Ndemera The

Traditional Medical Practitioner in Zimbabwe Mambo PressGweru Zimbabwe 1985

[20] B E VanWyk and N Gericke rsquoPeoplersquos PlantsmdashA Guide toUseful Plants of South Africa Briza Publication Pretoria SouthAfrica 2000

[21] A Hutchings A H Scott G Lewis and A CunninghamZulu Medicinal Plants An Inventory University of Natal PressScottsville South Africa 1996

[22] B E van Wyk B van Oudtshoorn and N Gericke MedicinalPlants of South Africa Briza Publications Pretoria SouthAfrica 1997

[23] J A Guillarmod Flora of Lesotho J Cramer Lehre Germany1971

[24] L I Somova F O Shode K Moodley and Y GovenderldquoCardiovascular and diuretic activity of kaurene derivativesof Xylopia aethiopica and Alepidea amatymbicardquo Journal ofEthnopharmacology vol 77 no 2-3 pp 165ndash174 2001

[25] J Pujol NaturAfrica The Herbalists Handbook Jean PujolNatural Healers Foundation Durban South Africa 1990

[26] A Hutchings and J van Staden ldquoPlants used for stress-relatedailments in traditional Zulu Xhosa and Sotho medicine Part 1plants used for headachesrdquo Journal of Ethnopharmacology vol43 no 2 pp 89ndash124 1994

[27] A Hutchings ldquorsquoObservations on plant usage in Xhosa and Zulumedicinerdquo Bothalia vol 19 pp 225ndash235 1989

[28] J F Sobiecki ldquoA preliminary inventory of plants used forpsychoactive purposes in southern African healing traditionsrdquoTransactions of the Royal Society of SouthAfrica vol 57 pp 1ndash242002

[29] S O Bandeira F Gaspar and F P Pagula ldquoAfrican ethnobotanyand healthcare emphasis on Mozambiquerdquo PharmaceuticalBiology vol 39 pp 70ndash73 2001

[30] A Rustaiyan and A S Sadjadi ldquoKaurene derivatives fromAlepidea amatynsiardquo Phytochemistry vol 26 no 7 pp 2106ndash2107 1987

[31] C W Holzapfel B E van Wyk A de Castro W Marais andM Herbst ldquoA chemotaxonomic survey of kaurene derivativesin the genus Alepidea (Apiaceae)rdquo Biochemical Systematics andEcology vol 23 no 7-8 pp 799ndash803 1995

[32] D K Olivier B van Wyk and F R van Heerden ldquoThechemotaxonomic and medicinal significance of phenolic acidsin Arctopus and Alepidea (Apiaceae subfamily Saniculoideae)rdquoBiochemical Systematics and Ecology vol 36 no 9 pp 724ndash7292008

[33] G I Stafford A K Jager and J van Staden ldquoEffect ofstorage on the chemical composition and biological activityof several popular South African medicinal plantsrdquo Journal ofEthnopharmacology vol 97 no 1 pp 107ndash115 2005

[34] C Clarkson V JMaharaj N R Crouch et al ldquoIn vitro antiplas-modial activity of medicinal plants native to or naturalised inSouth Africardquo Journal of Ethnopharmacology vol 92 no 2-3pp 177ndash191 2004

[35] F T TreurnichtAn evaluation of the toxic and potential antiviraleffects of some plants used by South Africans for medicinalpurposes [MS thesis] University of Stellenbosch StellenboschSouth Africa 1997

[36] A Hutchings Zulu Medicinal Plants Natal University PressPietermaritzburg South Africa 1996

[37] C I Wright L van-Buren C I Kroner and M M GKoning ldquoHerbalmedicines as diuretics a reviewof the scientificevidencerdquo Journal of Ethnopharmacology vol 114 no 1 pp 1ndash312007

[38] F O Shode and B C Rogers ldquoThe chemistry of ApiaceaeIsolation and characterisation of diterpenoids and other ter-penoids from Alepidea amatymbicardquo in Proceedings of the 7thInternational Chemistry Conference in Africa Durban SouthAfrica 1998

[39] C W Fennell M E Light S G Sparg G I Stafford and JVan Staden ldquoAssessingAfricanmedicinal plants for efficacy andsafety agricultural and storage practicesrdquo Journal of Ethnophar-macology vol 95 no 2-3 pp 113ndash121 2004

[40] D Luseba E E Elgorashi D T Ntloedibe and J Van StadenldquoAntibacterial anti-inflammatory and mutagenic effects ofsome medicinal plants used in South Africa for the treatmentof wounds and retained placenta in livestockrdquo South AfricanJournal of Botany vol 73 no 3 pp 378ndash383 2007

Submit your manuscripts athttpwwwhindawicom

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Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MEDIATORSINFLAMMATION

of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Behavioural Neurology

EndocrinologyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Disease Markers

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

OncologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Oxidative Medicine and Cellular Longevity

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

PPAR Research

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

ObesityJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Computational and Mathematical Methods in Medicine

OphthalmologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Diabetes ResearchJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Research and TreatmentAIDS

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Gastroenterology Research and Practice

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Parkinsonrsquos Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom

Page 4: Review Article Alepidea amatymbica Eckl. & Zeyh.: A Review ...downloads.hindawi.com/journals/ecam/2014/284517.pdf · A Review of Its Traditional Uses, Phytochemistry, Pharmacology,

4 Evidence-Based Complementary and Alternative Medicine

H3C CH2

CH2

O OH COOHOAc

Me

Me

R

R

R

SSS H

HHO2C

Ent-kaur-16-en-19-oic acid

16120572-Methoxy-ent-kaur-en-19-oic acid

15120573-Acetoxy-(mdash)-kaur-16-en-19-oic acid

Sources (ChemSpider sigma-Aldrich and Google)

Figure 2 Chemical structures of kaurene-type diterpenoids in Alepidea amatymbica

Table 2 Chemical groups part of the plant studied and isolated compounds isolated from Alepidea amatymbica Eckl amp Zeyh

Phytochemicals Compound Plant part Reference

Terpenes(kaurene-type diterpenoids)

ent-9 (11)-dehydro-16-kauren-19-oic acid Rhizomes and roots [30 31]ent-16-kauren-19-oic acid Dried rhizomes [30]wedelia seco-kaurenolide Dried rhizomes [12 30]313-acetoxy Dried rhizomes [30]

Phenolic acid Phenolic acid Rhizome [32]Rosmarinic acid 31015840-O-120573-d-Glucopyranosyl rosmarinic acid Rhizome [2]

have low activity (MIC value gt 1mgmL) [6]The dosage andMIC of the plant extract used in this study showed activityagainst the bacterial tested when compared to the controlThis suggests that the result favors its usage in traditionalmedicine for the treatment of bacterial infections

In a related work the crude extracts of the leaf stemrhizome and root of A amatymbica exhibit a range of anti-microbial properties against the following bacteria Bacilluscereus Staphylococcus epidermidis Staphylococcus aureusMicrococcus kristinae Streptococcus pyogenes Escherichiacoli Salmonella poona Serratia marcescens Pseudomonasaeruginosa and Klebsiella pneumoniaeThe acetone rhizomeextract showed better activity than others especially on Saureus and B cereus and moderate activity was recordedagainst the gram-positive bacteria tested with the exceptionofMicrococcus kristinae [8] Although the inhibitionwas highin all the parts of the plant tested the acetone and methanolstem extract showed a weak activity against Streptococcuspyogenes This result supports the use of A amatymbicain treating bacterial diseases associated with respiratorytract urinary tract and gastrointestinal tract infections Dueto lack of positive control in this work it is difficult to

draw conclusions on the study Thus further investigation isrequired to justify its traditional usage as antibacterial

The fresh and 90-day dried crude extract of the leafand rhizome extract of A amatymbica prepared in waterethanol and hexane were used in this study [9] The extractsdemonstrated anti-H pylori activity with zone of inhibitionrange of 0ndash38mm and MIC

50range of 006ndash50mgmL

respectively The antimicrobial activity was comparable withthe control antibiotics HoweverA amatymbica extracts gavea susceptibility of less than 50

The antibacterial activity also increased with storage orageing of plant material [33] Antibacterial activity is stablein dry specimens and as such may account for the factthat activity is unaffected by storage in certain instances[39] Therefore the result favors the use of the plant as anantibacterial considering the activity of the extract and thecontrol even though the dosage was not stated Hence morework is needed in the validation of the plant extract for thetreatment of bacterial infections

52 Antifungal Activity Antifungal activities of A amatym-bica have been reported [6 8] The crude extracts of the leaf

Evidence-Based Complementary and Alternative Medicine 5

Table3Ph

armacologicalinvestigationof

Alepidea

amatym

bica

Ecklamp

Zeyh

Activ

ityteste

dMod

elused

Plantp

art

usedte

sted

material

Extracttype

Dosage

Con

trol

Results

Reference

Antibacteria

l

Nutrie

ntagar

medium

was

mixed

with

extractand

bacteriasuspensio

nSpeciesstrainsB

acillus

subtilisA

TCC6051

and

Staphylococcus

aureus

ATCC

1260

0and

Escherich

iacoliAT

CC117

75andKlebsiella

pneumoniae

ATCC

13883

Rhizom

eDCM

PE

waterand

EtOHrhizom

eextracts

1mgm

LWater

andbacteriafre

ebroth(minusve)01m

gmL

neom

ycin

(+ve)

TheP

EandDCM

extracts

ofther

hizomes

exhibited

theb

estactivity

(MIC

values

of039

mgmL)

againstB

subtilis

Ther

est

ofthee

xtractssho

wedlow

activ

ity(M

ICvalues

gt1m

gmL)

[6]

Antibacteria

l

Agard

ilutio

nmetho

dswith

thefollowingorganism

sBa

cilluscereus

Staphylococcus

epidermidis

Staphylococcus

aureus

Micrococcusk

ristin

ae

Streptococcusp

yogenes

Escherich

iacoliSalm

onella

poonaSerratiamarcescens

Pseudomonas

aeruginosa

andKlebsiella

pneumoniae

Crud

eextractso

ftheleafste

m

rhizom

eandroot

Aceton

eand

methano

l1ndash10mgmL

Plates

containing

1aceton

eand

methano

lin

agar

Thea

cetone

rhizom

eextractsho

wed

bette

ractiv

itythan

others

especiallyon

Saureus

and

Bcereus

mod

eratea

ctivity

thatwas

recorded

againstthe

gram

-positive

bacteria

teste

dwith

thee

xceptio

nof

Micrococcusk

ristin

ae

[8]

Antim

icrobial

Microdilutio

nmetho

don

Mueller-Hintonbroth

SpeciesB

acillus

subtilis

Staphylococcus

aureus

Escherich

iacoliand

Klebsiella

pneumoniae

Rhizom

eand

leaf

(fresh90

days

old

andon

e-year-o

ldmaterial)were

assayed

Waterethanoland

hexane

extracts

125625313156

078039

020and

01m

gmL

Extract-frees

olutionand

ethano

lwereu

sedas

ablankcontroland

neom

ycin

(+ve)

Thew

ater

extractsof

plants

teste

dfora

ntibacteria

lactiv

ityshow

edno

activ

ity

whereas

thee

thanol

extractsgenerally

show

edan

increase

inactiv

ityTh

eantib

acteria

lactivity

increase

with

storage

orageing

ofplantm

aterial

[33]

Antim

icrobial

Agarw

elldiffu

sionmetho

dusingHpyloriino

cula

prepared

atMcFarland

rsquosturbidity

standard

2was

plated

onto

BHIa

gar

supp

lementedwith

5ho

rseb

lood

andSkirr

owrsquos

supp

lement

Rootsrhizom

esEthylacetateacetone

ethano

lmethano

landwater

100m

gmL

Clarith

romycin

and10

DMSO

wereu

sedas

positivea

ndnegativ

econtrols

respectiv

ely

Thep

lantsd

emon

strated

anti-Hpyloriactivity

with

zone

diam

eterso

finhibitio

nbetween0and

38mm

and50minim

uminhibitory

concentration

(MIC50)v

aluesranging

from

006

to50m

gmL

[9]

6 Evidence-Based Complementary and Alternative MedicineTa

ble3Con

tinued

Activ

ityteste

dMod

elused

Plantp

art

usedte

sted

material

Extracttype

Dosage

Con

trol

Results

Reference

Antim

icrobial

Agarw

elldiffu

sionmetho

dAlepidea

amatym

bica

were

investigated

against30

clinicalstrains

ofHpylori

Rootsrhizom

esEthylacetateacetone

ethano

lmethano

landwater

0002ndash50m

gmL

Referencec

ontro

lstrain

(NCT

C116

38)

Metronidazoleand

amoxicillin

wereincluded

aspo

sitivec

ontro

lantib

iotic

s

Methano

lwas

quantitatively

theb

est

solventfor

allthe

plants

whileethylacetatehadthe

lowestyieldsA

amatym

bica

gave

percentage

susceptib

ilitie

sof

lessthan

50

[9]

Antifu

ngal

Agard

ilutio

nmetho

dswith

thefollowingorganism

sAspergillus

flavus

Aspergillus

nigerand

Penicilliu

mnotatum

cultu

resw

erem

aintained

onPo

tato

Dextro

seagar

Crud

eextractso

ftheleafste

m

rhizom

eandroot

Aceton

eand

methano

l

Radialpatte

rnof

streakingof

organism

swas

used

Plates

containing

onlyPD

Aor

PDAwith

ther

espective

solvent

Diameter

ofthefun

gal

grow

thwas

measuredand

expressedas

percentage

grow

thinhibitio

nAllthe

extractsshow

edmorethan

50mycoticinhibitio

nwith

activ

ityrang

ingfro

m5139

to

8111at

5mgmLwith

ther

hizome

[8]

Antifu

ngal

Thea

ntifu

ngalactiv

ityof

thee

xtractsw

asevaluated

againstC

andida

albicans

(ATC

C10231)andfung

alcultu

rewas

prepared

inYeastM

alt(YM

)

Rhizom

eDCM

PE

waterand

EtOHrhizom

eextracts

01ndash50m

gmL

Water

andbacteriafre

ebroth(minusve)01m

gmL

neom

ycin

(+ve)

Allthee

xtractssho

wed

activ

ityagainstC

andida

albicans

[6]

Anti-infl

ammatory

Usin

gthee

nzym

ebased

cyclo

oxygenasea

ssays

COX-

1and

COX-

2Rh

izom

eDCM

PE

waterand

EtOHrhizom

eextracts

1mgmL

Water

andbacteriafre

ebroth(minusve)01m

gmL

neom

ycin

(+ve)

TheP

EandDCM

extracts

hadhigh

COX-

1activity

with

percentage

inhibitio

nsabove7

0E

thanol

extractshadinhibitio

nless

than

40

[6]

Antihypertensive

Purifi

edcompo

unds

onbloo

dpressure

andheart

rateof

anesthetized

Wistar

rats

Freshrhizom

es

Hexanee

xtractive

(AA1)

dichloromethane

extractiv

eand

methano

lextractive

ipinjectio

nof

sodium

thiopenton

e(40m

gkg

body

weight)

Chlorothiazide

Inadditio

nto

the

cardiovascular

effects

distinctdiureticand

natriuretic

effectswere

foun

d

[24]

Antiplasm

odium

Plasmodium

falciparum

strainD10

usingthe

parasitelactate

dehydrogenase(pL

DH)

assay

Who

leplant

Dichlorom

ethane

(DCM

)DCM

methano

l(M

eOH)(11)

MeO

Hand

purifi

edwater

100ndash

02120583

gmL)

Chloroqu

ined

ipho

sphate

served

asthep

ositive

control

Detectp

lant-based

antim

alarialagents

show

ingprom

ising

antip

lasm

odialactivity

with

IC50

values

ofle10gmL

[34]

Diuretic

TheL

ipschitztestwas

used

todeterm

inethe

Diuretic

andsaluretic

activ

ityin

rats

Freshrhizom

eHexaneethylacetate

extract

Thetestcom

poun

dwas

appliedorallyata

dose

of50

mgkg

Urea(

1gkgb

w)

Hydrochlorothiazide

(25m

gkg

bw)

Thed

iuretic

andnatriuretic

effectsof

thee

xtractives

werefou

ndto

besim

ilarto

thee

ffectso

fchlorothiazide

[24]

Evidence-Based Complementary and Alternative Medicine 7

Table3Con

tinued

Activ

ityteste

dMod

elused

Plantp

art

usedte

sted

material

Extracttype

Dosage

Con

trol

Results

Reference

Cardiovascular

Purifi

edcompo

unds

onbloo

dpressure

andheart

rateof

anesthetized

Wistar

rats

Purifi

edcompo

undfro

mfre

shrhizom

e

Hexanee

xtract

(AA1)

dichloromethaneand

methano

lportio

nof

AA1weres

ubjected

torepeated

flash

chromatograph

ywith

gradient

elutio

n(100ndash70

hexaneEtO

Ac)to

give

AA3a

crystalline

mixture

ofent-k

aur-en-19-oic

acident-kaura-9

(11)

16-dien-19-oicacid

and

trachyloban-19-oic

acidA

A4

16-m

etho

xy-ent-kaur-

11-en-19-oica

cid

AA511-a

cetoxy-ent-

kaur-16-en-19-oic

acidand

AA6

wedelia

seco-kaureno

lide

20mgkg

bw

intraperito

neally

Ethylene

glycol

Mod

eratebu

tsignificant

decreasin

gsysto

licbloo

dpressure

(SBP

)and

heart

rate(H

T)effectsaft

erintraperito

nealapplication

onconsciou

srats

[24]

Anti-H

IV

Extractsandtherein

subfractions

ofA

amatym

bica

werea

ssessed

inac

ellbased

assay

targetingther

eplicationof

prototypicCX

CR4-tro

pic

(NL4

-3)o

rCCR

5-tro

pic

(NL-AD87)H

IV-1str

ains

Aeria

lpartsand

roots

Aqueou

s500120583

Lof

samplea

taconcentrationof

25mgmL

Standard

retro

viral

inhibitor

Thea

ctiveing

redient

identifi

edin

thea

queous

extractd

oesn

otsupp

orta

directapplicationof

this

plantextractfortreating

HIV

infection

The

anti-HIV

activ

ityof

the

pure

compo

undwas

foun

dto

bequ

itemod

erate

[212]

Antihelminthes

Nem

atod

egrowth

agar

with

Caenorhabditiseleg

ans

varBristol(N

2)nematod

es

Freshandsto

red

leaves

androot

Ethano

l1m

gmL

Levamiso

le(+Ve

)and

nematod

eincub

ated

with

water

(minusVe

)

Onlyfre

shandsto

redwater

extractsshow

eda

significantantihelminthes

[33]

8 Evidence-Based Complementary and Alternative Medicine

Table3Con

tinued

Activ

ityteste

dMod

elused

Plantp

art

usedte

sted

material

Extracttype

Dosage

Con

trol

Results

Reference

Toxicity

Theb

acteria

lcultures

(100120583L)

werea

dded

to100120583

Lof

plantextractin

500120583

Lph

osph

ateb

uffer

and2m

Lof

agar

containing

biotin-histidine(05m

M)

Rhizom

eDCM

PE

waterand

EtOHrhizom

eextracts

50500and

5000120583gmL

4-Nitroq

uino

line-N-oxide

(4NQO)w

asused

asa

positivec

ontro

land

water

(minusve

control)

TheA

mes

testrevealed

that

none

ofthep

lant

extracts

significantly

increasedthe

numbero

fHis+

revertants

with

respecttothen

egative

control

[6]

Cytoxicity

HeLaVe

roJurkatE

61

AA-

2or

CEM-SScells

Freshrhizom

esAq

ueou

s1m

gmL

Not

stated

Thee

xtractwas

nottoxicat

anyconcentrationused

inthetest

[35]

Acutetoxicity

Evaluatio

nusingbrine

shrim

pAr

temiasalin

aintersectio

nbioassay

Freshrhizom

esHexane

Not

stated

Not

stated

Theb

rines

hrim

ptest

show

edthatthec

rude

hexane

extractshave

low

toxicitywith

LC5002

[24]

Toxicity

TheH

ippo

craticteston

rats

was

used

Freshrhizom

esIsolates

from

Alepidea

amatym

bica

Hexanee

xtractive

01m

gmL

Verapamil(10m

gkg)

Allextracts

crud

eand

purifi

edsho

wed

low

toxicityrang

ingfro

mLC

5005to

5ngmLapartfrom

AA4

andAA5

that

prod

uced

slightd

iarrheao

ndays

34and5andother

extractiv

esshow

edno

toxicityatad

oseo

f20

[24]

Evidence-Based Complementary and Alternative Medicine 9

stem rhizome and root exhibited activity against Candidaalbicans extracts and more than 50 mycotic inhibitionagainst fungal cultures [6] This study does not provide adose dependent evidence of the extract and negative controlwas not used in validating the traditional use of the plantas antifungal Also all the extracts except acetone extractshowed mycotic inhibition activity against Aspergillus flavusandAspergillus niger [8]These results validate the traditionaluses of the plant as an antifungal but no dose dependentevidencewas given in this study and positive control drugwasnot used in comparison with the extract used Therefore theantifungal activity of the extract cannot be compared with anantifungal drug

53 Antiviral Louvel et al [2] investigated the screeningactivity of the aerial part and root aqueous extract of Aamatymbica against a cell-based infection assay targeting thereplication of prototypic CXCR4-tropic (NL4-3) or CCR5-tropic (NL-AD87) HIV-1 strains designed to detect inhibitorsblocking any step of the viral life cycle The active ingredientidentified in the extract does not support a direct applicationof this plant extract for treating HIV infection The anti-HIV activity of the pure compound was found to be quitemoderate Lack of negative control and a dose dependentactivity of the extract make the antiviral activity of the extractinconclusive

54 Antihelminthes Research was undertaken using nema-tode growth agar with Caenorhabditis elegans var Bristol(N2)nematodes on the ethanol extract of the fresh and storedleaves and root ofA amatymbicaOnly fresh and storedwaterextracts showed a significant Anthelminthic [33] The resultof the study did not evaluate a dose dependent inhibitionof the extract against the worms even though the controlswere compared with the extract Further investigation isthus required to validate the use of the plant in traditionalmedicine as antihelmintic

55 Anti-Inflammatory The DCM PE water and EtOHrhizome extracts were evaluated using the enzyme basedcyclooxygenase assays COX-1 and COX-2 [6] The PE andDCM extracts had high COX-1 and COX-2 activities withpercentage inhibitions above 70 Ethanol extracts showedhigher inhibition (lt40) in COX-1 than COX-2 The waterextract on the other hand has a moderate inhibition activ-ity (40ndash60) in COX-1 and lowered in COX-2 (lt20)Despite reports on the undesirable effects of higher COX-1 inhibition as a result of its damage to the gastrointestinaltract [40] report of Mulaudzi et al [6] recorded a higherCOX-1 in both DCM and PE and a lower COX-1 inhibitionin ethanol and water The result favors the use of waterand ethanol as a solvent of extraction for this plant whenusing it against inflammation However conclusion cannotbe totally drawn on this report due to lack of negativecontrol and dosage Hence further investigation is required toprovide an evidence for its traditional use against inflamma-tion

56 Antihypertensive Hexane extractive (AA1) dichloro-methane extractive and methanol extractive of the fresh rhi-zome were investigated using purified compounds on bloodpressure and heart rate of anesthetizedWistar rats Moderatebut significant decrease in systolic blood pressure (SBP) andheart rate (HT) effects after intraperitoneal application onconscious rats was reported [24]

57 Antiplasmodium Dichloromethane (DCM) DCMmethanol (MeOH) (1 1) MeOH and purified water extractfrom the whole plant were investigated on plasmodialactivity and were found to contain plant based antimalarialagents showing promising antiplasmodial activity with IC

50

values of le10 gmL [34] This is the only study showing thedose dependent antiplasmodic activity of the plant extractin relation to the positive control Validation of the use ofthe plant in vivo is necessary to conclude the antiplasmodialactivity of A amatymbica

58 Diuretic The purified compounds of the fresh rhizomeextracted in hexaneethyl acetate of A amatymbica wereinvestigated using anesthetized Wistar rats The diuretic andnatriuretic effects of the extractives were found to be similarto the effects of chlorothiazide drug [24] The result suggeststhe inhibitory effect of the extractive of A amatymbica inreabsorption of K+ and Na+ ions suggesting the diureticand natriuretic effects of the extractives Lack of testedextractive in a dose dependent manner however negates thevalidation of the plants and the extractives for use as diuretictraditionally Further investigation is required to provideevidence for its use as a diuretic

6 Toxicological Reports

Four toxicity screens were identified in the literature Eachof the four screens tested uses crude aqueous and organicsolvents hexane extracts and extractives from the crudehexane extract and none of the reports recorded toxicity atall doses testedThe reported cytotoxicity of the fresh aqueousrhizome was investigated using HeLa Vero and Jurkat E61AA-2 or CEM-SS cells The extract was shown not to betoxic at all concentrations used in the test [35] since thedosage and controls were shown in this study in comparisonwith the control The second screens use bacterial cultures(100 120583L) in an Amen test assay which were added to 100120583L ofDCM PE water and EtOH rhizome plant extracts in 500120583Lphosphate buffer and 2mLof agar containing biotin-histidine(05mM) The Ames test revealed that none of the plantextracts significantly increased the number ofHis+ revertantswith respect to the negative control [6] The third test screenutilised the Brine Shrimp Lethal Assay (BSLA) Acute toxicityof the isolates from Alepidea amatymbica was screen againstbrine shrimp Artemia salina intersection bioassay The brineshrimp test showed that the crude hexane extracts have lowtoxicity with LC

5002 ngmL while the AA6 (wedelia seco-

kaurenolide) a derivative of A amatymbica has a low toxicityof 05 ngmL [24]The fourth screenmade use of Hippocratictest on rats with the use of hexane (AA1) extract and itrsquos

10 Evidence-Based Complementary and Alternative Medicine

extractives in dichloromethane and methanol (AA1) aftersubjection to repeated flash chromatography with gradientelution (100ndash70 hexaneEtOAc) to give AA3 a crystallinemixture of ent-kaur-en-19-oic acid ent-kaura-9 (11) 16-dien-19-oic acid and trachyloban-19-oic acid AA4 16-methoxy-ent-kaur-11-en-19-oic acid AA5 11-acetoxy-ent-kaur-16-en-19-oic acid and AA6 wedelia seco-kaurenolide All extractscrude and purified showed low toxicity ranging from 05 to5 ngmL (LC

50) apart from AA4 and AA5 that produced

slight diarrhea on days 3 4 and 5 and other extractivesshowed no toxicity at a dose of 20 [24] Apart from thestudies of Treurnicht [35] and Mulaudzi et al [6] mentionedabove the other studies do not provide sufficient evidencewith respect to the safety of A amatymbica considering theabsence of dosage used and control in their assays

7 Clinical Trials

To date there appears to be no published research indicatingthat extracts ofAlepidea amatymbica have undergone humanclinical trials

8 Conclusion

The review showed that A amatymbica has a widespread usein South Africa and other SADEC countriesThe recognitionof its ethnomedicinal usage for conditions of inflammationlike rheumatism and sore throat to usage for wounds coughasthma influenza diarrhea stomach cramps abdominal dis-orders malaria and diuretic is worth mentioningThe abilityof the extract to also restrain the growth of bacteria and fungiindicated its broad spectrum antimicrobial prospective Thepharmacological reports on A amatymbica revealed thera-peutic potential in the treatment of inflammation malariaand infectious diseases like influenza cough and diarrheaThe frequently occurring chemical constituents of Alepideaamatymbica belong to the kaurene-type diterpenoids andtheir derivatives Literature search onA amatymbica revealedthe use of cell line brine shrimps and rats for the determi-nation of the toxicity in the plant More investigations arenecessary to explore themedicinal potential of the plant in themanagement of rheumatism asthma hypertension diureticand inflammation Clinical trials and product development tofully exploit the medicinal value are also required to validateits folklore use in traditional medicine There is thereforethe need to develop the existing traditional use of this plantto amplify nutraceuticals product and commence clinicalresearch to exploit the plantrsquos novel phytochemicals

Conflict of Interests

The authors declare no conflict of interests

Acknowledgments

The authors are thankful to the Govan Mbeki Research andDevelopment Centre and the National Research Fund of theUniversity of Fort Hare South Africa

References

[1] B l Burtt ldquoUmbelliferae of southern Africa an introductionand annotated checklistrdquo Edinburgh Journal of Botany vol 48pp 133ndash282 1991

[2] S Louvel N Moodley I Seibert et al ldquoIdentification ofcompounds from the plant species Alepidea amatymbica activeagainst HIVrdquo South African Journal of Botany vol 86 pp 9ndash142013

[3] G Germishuizen N L Meyer Y Steenkamp and M KeithPlants of Southern Africa An Annotated Checklist vol 41 ofSABONET Report National Botanical Institute Pretoria SouthAfrica 2006

[4] R R Klopper P Lemmer and J Nel ldquoPteridophyta Pteridaceaecheilanthes deltoidea a new locality in Gauteng South AfricardquoBothalia vol 36 no 2 pp 173ndash174 2006

[5] Z Maksimovic S Dobric N Kovacevic and Z MilovanovicldquoDiuretic activity of Maydis stigma extract in ratsrdquo Pharmazievol 59 no 12 pp 967ndash971 2004

[6] R B Mulaudzi A R Ndhlala J F Finnie and J Van StadenldquoAntimicrobial anti-inflammatory and genotoxicity activityof Alepidea amatymbica and Alepidea natalensis (Apiaceae)rdquoSouth African Journal of Botany vol 75 no 3 pp 584ndash587 2009

[7] A de Castro and B-E van Wyk ldquoDiagnostic characters andgeographic distribution of Alepidea species used in traditionalmedicinerdquo South African Journal of Botany vol 60 no 6 pp345ndash350 1994

[8] A J Afolayan and F B Lewu ldquoAntimicrobial activity ofAlepideaamatymbicardquo Pharmaceutical Biology vol 47 no 5 pp 436ndash439 2009

[9] C Njume A A Jide and R N Ndip ldquoAqueous and organicsolvent-extracts of selected South African medicinal plantspossess antimicrobial activity against drug-resistant strainsof Helicobacter pylori inhibitory and bactericidal potentialrdquoInternational Journal of Molecular Sciences vol 12 no 9 pp5652ndash5665 2011

[10] J M Watt and M G Breyer-Brandwijik The Medicinal andPoisonous Plants of Southern and Eastern Africa E and SLivingstone London UK 2nd edition 1962

[11] B E van Wyk A de Castro P M Tilney P J D Winter andA R Magee ldquoA new species of Alepidea (Apiaceae subfamSaniculoideae)rdquo South African Journal of Botany vol 74 no 4pp 740ndash745 2008

[12] J T Mukinda and P F K Eagles ldquoThe South African Pharma-copoeia Monograph Projectrdquo Developed by South African Tra-ditional Medicines Research Group (SATMERG) and Schoolof Pharmacy University of the Western Cape (Unpublished)2010

[13] A Mapaura and J R Timberlake ldquoSouthern African plantred data listsrdquo Southern African Botanical Diversity Network(SABONET) Report 14 SABONET Pretoria South Africa

[14] A Maroyi ldquoEthnobotanical study of two threatened medicinalplants in Zimbabwerdquo International Journal of Biodiversity Sci-ence and Management vol 4 no 3 pp 148ndash153 2008

[15] S Talukdar ldquoLesothordquo in Southern African Plant Red Data ListsJ Golding Ed Southern African Botanical Diversity Network(SABONET) Report Number 14 pp 21ndash30 SABONET Preto-ria South Africa 2002

[16] R Scott-Shaw ldquoRare and threatened plants of KwaZulu-Nataland neighbouring regionsrdquo in A Plant Red Data Book p182 KwaZulu-Natal Nature Conservation Service Pietermar-itzburg South Africa 1999

Evidence-Based Complementary and Alternative Medicine 11

[17] The Plant List 2012 httpwwwtheplantlistorg[18] S Nonjinge and B B Tarr Natal National Botanical Garden

2013 httpwwwplantzafricacomplantabalipedeamathtm[19] M Gelfand S Mavi R B Drummond and B Ndemera The

Traditional Medical Practitioner in Zimbabwe Mambo PressGweru Zimbabwe 1985

[20] B E VanWyk and N Gericke rsquoPeoplersquos PlantsmdashA Guide toUseful Plants of South Africa Briza Publication Pretoria SouthAfrica 2000

[21] A Hutchings A H Scott G Lewis and A CunninghamZulu Medicinal Plants An Inventory University of Natal PressScottsville South Africa 1996

[22] B E van Wyk B van Oudtshoorn and N Gericke MedicinalPlants of South Africa Briza Publications Pretoria SouthAfrica 1997

[23] J A Guillarmod Flora of Lesotho J Cramer Lehre Germany1971

[24] L I Somova F O Shode K Moodley and Y GovenderldquoCardiovascular and diuretic activity of kaurene derivativesof Xylopia aethiopica and Alepidea amatymbicardquo Journal ofEthnopharmacology vol 77 no 2-3 pp 165ndash174 2001

[25] J Pujol NaturAfrica The Herbalists Handbook Jean PujolNatural Healers Foundation Durban South Africa 1990

[26] A Hutchings and J van Staden ldquoPlants used for stress-relatedailments in traditional Zulu Xhosa and Sotho medicine Part 1plants used for headachesrdquo Journal of Ethnopharmacology vol43 no 2 pp 89ndash124 1994

[27] A Hutchings ldquorsquoObservations on plant usage in Xhosa and Zulumedicinerdquo Bothalia vol 19 pp 225ndash235 1989

[28] J F Sobiecki ldquoA preliminary inventory of plants used forpsychoactive purposes in southern African healing traditionsrdquoTransactions of the Royal Society of SouthAfrica vol 57 pp 1ndash242002

[29] S O Bandeira F Gaspar and F P Pagula ldquoAfrican ethnobotanyand healthcare emphasis on Mozambiquerdquo PharmaceuticalBiology vol 39 pp 70ndash73 2001

[30] A Rustaiyan and A S Sadjadi ldquoKaurene derivatives fromAlepidea amatynsiardquo Phytochemistry vol 26 no 7 pp 2106ndash2107 1987

[31] C W Holzapfel B E van Wyk A de Castro W Marais andM Herbst ldquoA chemotaxonomic survey of kaurene derivativesin the genus Alepidea (Apiaceae)rdquo Biochemical Systematics andEcology vol 23 no 7-8 pp 799ndash803 1995

[32] D K Olivier B van Wyk and F R van Heerden ldquoThechemotaxonomic and medicinal significance of phenolic acidsin Arctopus and Alepidea (Apiaceae subfamily Saniculoideae)rdquoBiochemical Systematics and Ecology vol 36 no 9 pp 724ndash7292008

[33] G I Stafford A K Jager and J van Staden ldquoEffect ofstorage on the chemical composition and biological activityof several popular South African medicinal plantsrdquo Journal ofEthnopharmacology vol 97 no 1 pp 107ndash115 2005

[34] C Clarkson V JMaharaj N R Crouch et al ldquoIn vitro antiplas-modial activity of medicinal plants native to or naturalised inSouth Africardquo Journal of Ethnopharmacology vol 92 no 2-3pp 177ndash191 2004

[35] F T TreurnichtAn evaluation of the toxic and potential antiviraleffects of some plants used by South Africans for medicinalpurposes [MS thesis] University of Stellenbosch StellenboschSouth Africa 1997

[36] A Hutchings Zulu Medicinal Plants Natal University PressPietermaritzburg South Africa 1996

[37] C I Wright L van-Buren C I Kroner and M M GKoning ldquoHerbalmedicines as diuretics a reviewof the scientificevidencerdquo Journal of Ethnopharmacology vol 114 no 1 pp 1ndash312007

[38] F O Shode and B C Rogers ldquoThe chemistry of ApiaceaeIsolation and characterisation of diterpenoids and other ter-penoids from Alepidea amatymbicardquo in Proceedings of the 7thInternational Chemistry Conference in Africa Durban SouthAfrica 1998

[39] C W Fennell M E Light S G Sparg G I Stafford and JVan Staden ldquoAssessingAfricanmedicinal plants for efficacy andsafety agricultural and storage practicesrdquo Journal of Ethnophar-macology vol 95 no 2-3 pp 113ndash121 2004

[40] D Luseba E E Elgorashi D T Ntloedibe and J Van StadenldquoAntibacterial anti-inflammatory and mutagenic effects ofsome medicinal plants used in South Africa for the treatmentof wounds and retained placenta in livestockrdquo South AfricanJournal of Botany vol 73 no 3 pp 378ndash383 2007

Submit your manuscripts athttpwwwhindawicom

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Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MEDIATORSINFLAMMATION

of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Behavioural Neurology

EndocrinologyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Disease Markers

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

OncologyJournal of

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Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Oxidative Medicine and Cellular Longevity

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

PPAR Research

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

ObesityJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Computational and Mathematical Methods in Medicine

OphthalmologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Diabetes ResearchJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Research and TreatmentAIDS

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Gastroenterology Research and Practice

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Parkinsonrsquos Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom

Page 5: Review Article Alepidea amatymbica Eckl. & Zeyh.: A Review ...downloads.hindawi.com/journals/ecam/2014/284517.pdf · A Review of Its Traditional Uses, Phytochemistry, Pharmacology,

Evidence-Based Complementary and Alternative Medicine 5

Table3Ph

armacologicalinvestigationof

Alepidea

amatym

bica

Ecklamp

Zeyh

Activ

ityteste

dMod

elused

Plantp

art

usedte

sted

material

Extracttype

Dosage

Con

trol

Results

Reference

Antibacteria

l

Nutrie

ntagar

medium

was

mixed

with

extractand

bacteriasuspensio

nSpeciesstrainsB

acillus

subtilisA

TCC6051

and

Staphylococcus

aureus

ATCC

1260

0and

Escherich

iacoliAT

CC117

75andKlebsiella

pneumoniae

ATCC

13883

Rhizom

eDCM

PE

waterand

EtOHrhizom

eextracts

1mgm

LWater

andbacteriafre

ebroth(minusve)01m

gmL

neom

ycin

(+ve)

TheP

EandDCM

extracts

ofther

hizomes

exhibited

theb

estactivity

(MIC

values

of039

mgmL)

againstB

subtilis

Ther

est

ofthee

xtractssho

wedlow

activ

ity(M

ICvalues

gt1m

gmL)

[6]

Antibacteria

l

Agard

ilutio

nmetho

dswith

thefollowingorganism

sBa

cilluscereus

Staphylococcus

epidermidis

Staphylococcus

aureus

Micrococcusk

ristin

ae

Streptococcusp

yogenes

Escherich

iacoliSalm

onella

poonaSerratiamarcescens

Pseudomonas

aeruginosa

andKlebsiella

pneumoniae

Crud

eextractso

ftheleafste

m

rhizom

eandroot

Aceton

eand

methano

l1ndash10mgmL

Plates

containing

1aceton

eand

methano

lin

agar

Thea

cetone

rhizom

eextractsho

wed

bette

ractiv

itythan

others

especiallyon

Saureus

and

Bcereus

mod

eratea

ctivity

thatwas

recorded

againstthe

gram

-positive

bacteria

teste

dwith

thee

xceptio

nof

Micrococcusk

ristin

ae

[8]

Antim

icrobial

Microdilutio

nmetho

don

Mueller-Hintonbroth

SpeciesB

acillus

subtilis

Staphylococcus

aureus

Escherich

iacoliand

Klebsiella

pneumoniae

Rhizom

eand

leaf

(fresh90

days

old

andon

e-year-o

ldmaterial)were

assayed

Waterethanoland

hexane

extracts

125625313156

078039

020and

01m

gmL

Extract-frees

olutionand

ethano

lwereu

sedas

ablankcontroland

neom

ycin

(+ve)

Thew

ater

extractsof

plants

teste

dfora

ntibacteria

lactiv

ityshow

edno

activ

ity

whereas

thee

thanol

extractsgenerally

show

edan

increase

inactiv

ityTh

eantib

acteria

lactivity

increase

with

storage

orageing

ofplantm

aterial

[33]

Antim

icrobial

Agarw

elldiffu

sionmetho

dusingHpyloriino

cula

prepared

atMcFarland

rsquosturbidity

standard

2was

plated

onto

BHIa

gar

supp

lementedwith

5ho

rseb

lood

andSkirr

owrsquos

supp

lement

Rootsrhizom

esEthylacetateacetone

ethano

lmethano

landwater

100m

gmL

Clarith

romycin

and10

DMSO

wereu

sedas

positivea

ndnegativ

econtrols

respectiv

ely

Thep

lantsd

emon

strated

anti-Hpyloriactivity

with

zone

diam

eterso

finhibitio

nbetween0and

38mm

and50minim

uminhibitory

concentration

(MIC50)v

aluesranging

from

006

to50m

gmL

[9]

6 Evidence-Based Complementary and Alternative MedicineTa

ble3Con

tinued

Activ

ityteste

dMod

elused

Plantp

art

usedte

sted

material

Extracttype

Dosage

Con

trol

Results

Reference

Antim

icrobial

Agarw

elldiffu

sionmetho

dAlepidea

amatym

bica

were

investigated

against30

clinicalstrains

ofHpylori

Rootsrhizom

esEthylacetateacetone

ethano

lmethano

landwater

0002ndash50m

gmL

Referencec

ontro

lstrain

(NCT

C116

38)

Metronidazoleand

amoxicillin

wereincluded

aspo

sitivec

ontro

lantib

iotic

s

Methano

lwas

quantitatively

theb

est

solventfor

allthe

plants

whileethylacetatehadthe

lowestyieldsA

amatym

bica

gave

percentage

susceptib

ilitie

sof

lessthan

50

[9]

Antifu

ngal

Agard

ilutio

nmetho

dswith

thefollowingorganism

sAspergillus

flavus

Aspergillus

nigerand

Penicilliu

mnotatum

cultu

resw

erem

aintained

onPo

tato

Dextro

seagar

Crud

eextractso

ftheleafste

m

rhizom

eandroot

Aceton

eand

methano

l

Radialpatte

rnof

streakingof

organism

swas

used

Plates

containing

onlyPD

Aor

PDAwith

ther

espective

solvent

Diameter

ofthefun

gal

grow

thwas

measuredand

expressedas

percentage

grow

thinhibitio

nAllthe

extractsshow

edmorethan

50mycoticinhibitio

nwith

activ

ityrang

ingfro

m5139

to

8111at

5mgmLwith

ther

hizome

[8]

Antifu

ngal

Thea

ntifu

ngalactiv

ityof

thee

xtractsw

asevaluated

againstC

andida

albicans

(ATC

C10231)andfung

alcultu

rewas

prepared

inYeastM

alt(YM

)

Rhizom

eDCM

PE

waterand

EtOHrhizom

eextracts

01ndash50m

gmL

Water

andbacteriafre

ebroth(minusve)01m

gmL

neom

ycin

(+ve)

Allthee

xtractssho

wed

activ

ityagainstC

andida

albicans

[6]

Anti-infl

ammatory

Usin

gthee

nzym

ebased

cyclo

oxygenasea

ssays

COX-

1and

COX-

2Rh

izom

eDCM

PE

waterand

EtOHrhizom

eextracts

1mgmL

Water

andbacteriafre

ebroth(minusve)01m

gmL

neom

ycin

(+ve)

TheP

EandDCM

extracts

hadhigh

COX-

1activity

with

percentage

inhibitio

nsabove7

0E

thanol

extractshadinhibitio

nless

than

40

[6]

Antihypertensive

Purifi

edcompo

unds

onbloo

dpressure

andheart

rateof

anesthetized

Wistar

rats

Freshrhizom

es

Hexanee

xtractive

(AA1)

dichloromethane

extractiv

eand

methano

lextractive

ipinjectio

nof

sodium

thiopenton

e(40m

gkg

body

weight)

Chlorothiazide

Inadditio

nto

the

cardiovascular

effects

distinctdiureticand

natriuretic

effectswere

foun

d

[24]

Antiplasm

odium

Plasmodium

falciparum

strainD10

usingthe

parasitelactate

dehydrogenase(pL

DH)

assay

Who

leplant

Dichlorom

ethane

(DCM

)DCM

methano

l(M

eOH)(11)

MeO

Hand

purifi

edwater

100ndash

02120583

gmL)

Chloroqu

ined

ipho

sphate

served

asthep

ositive

control

Detectp

lant-based

antim

alarialagents

show

ingprom

ising

antip

lasm

odialactivity

with

IC50

values

ofle10gmL

[34]

Diuretic

TheL

ipschitztestwas

used

todeterm

inethe

Diuretic

andsaluretic

activ

ityin

rats

Freshrhizom

eHexaneethylacetate

extract

Thetestcom

poun

dwas

appliedorallyata

dose

of50

mgkg

Urea(

1gkgb

w)

Hydrochlorothiazide

(25m

gkg

bw)

Thed

iuretic

andnatriuretic

effectsof

thee

xtractives

werefou

ndto

besim

ilarto

thee

ffectso

fchlorothiazide

[24]

Evidence-Based Complementary and Alternative Medicine 7

Table3Con

tinued

Activ

ityteste

dMod

elused

Plantp

art

usedte

sted

material

Extracttype

Dosage

Con

trol

Results

Reference

Cardiovascular

Purifi

edcompo

unds

onbloo

dpressure

andheart

rateof

anesthetized

Wistar

rats

Purifi

edcompo

undfro

mfre

shrhizom

e

Hexanee

xtract

(AA1)

dichloromethaneand

methano

lportio

nof

AA1weres

ubjected

torepeated

flash

chromatograph

ywith

gradient

elutio

n(100ndash70

hexaneEtO

Ac)to

give

AA3a

crystalline

mixture

ofent-k

aur-en-19-oic

acident-kaura-9

(11)

16-dien-19-oicacid

and

trachyloban-19-oic

acidA

A4

16-m

etho

xy-ent-kaur-

11-en-19-oica

cid

AA511-a

cetoxy-ent-

kaur-16-en-19-oic

acidand

AA6

wedelia

seco-kaureno

lide

20mgkg

bw

intraperito

neally

Ethylene

glycol

Mod

eratebu

tsignificant

decreasin

gsysto

licbloo

dpressure

(SBP

)and

heart

rate(H

T)effectsaft

erintraperito

nealapplication

onconsciou

srats

[24]

Anti-H

IV

Extractsandtherein

subfractions

ofA

amatym

bica

werea

ssessed

inac

ellbased

assay

targetingther

eplicationof

prototypicCX

CR4-tro

pic

(NL4

-3)o

rCCR

5-tro

pic

(NL-AD87)H

IV-1str

ains

Aeria

lpartsand

roots

Aqueou

s500120583

Lof

samplea

taconcentrationof

25mgmL

Standard

retro

viral

inhibitor

Thea

ctiveing

redient

identifi

edin

thea

queous

extractd

oesn

otsupp

orta

directapplicationof

this

plantextractfortreating

HIV

infection

The

anti-HIV

activ

ityof

the

pure

compo

undwas

foun

dto

bequ

itemod

erate

[212]

Antihelminthes

Nem

atod

egrowth

agar

with

Caenorhabditiseleg

ans

varBristol(N

2)nematod

es

Freshandsto

red

leaves

androot

Ethano

l1m

gmL

Levamiso

le(+Ve

)and

nematod

eincub

ated

with

water

(minusVe

)

Onlyfre

shandsto

redwater

extractsshow

eda

significantantihelminthes

[33]

8 Evidence-Based Complementary and Alternative Medicine

Table3Con

tinued

Activ

ityteste

dMod

elused

Plantp

art

usedte

sted

material

Extracttype

Dosage

Con

trol

Results

Reference

Toxicity

Theb

acteria

lcultures

(100120583L)

werea

dded

to100120583

Lof

plantextractin

500120583

Lph

osph

ateb

uffer

and2m

Lof

agar

containing

biotin-histidine(05m

M)

Rhizom

eDCM

PE

waterand

EtOHrhizom

eextracts

50500and

5000120583gmL

4-Nitroq

uino

line-N-oxide

(4NQO)w

asused

asa

positivec

ontro

land

water

(minusve

control)

TheA

mes

testrevealed

that

none

ofthep

lant

extracts

significantly

increasedthe

numbero

fHis+

revertants

with

respecttothen

egative

control

[6]

Cytoxicity

HeLaVe

roJurkatE

61

AA-

2or

CEM-SScells

Freshrhizom

esAq

ueou

s1m

gmL

Not

stated

Thee

xtractwas

nottoxicat

anyconcentrationused

inthetest

[35]

Acutetoxicity

Evaluatio

nusingbrine

shrim

pAr

temiasalin

aintersectio

nbioassay

Freshrhizom

esHexane

Not

stated

Not

stated

Theb

rines

hrim

ptest

show

edthatthec

rude

hexane

extractshave

low

toxicitywith

LC5002

[24]

Toxicity

TheH

ippo

craticteston

rats

was

used

Freshrhizom

esIsolates

from

Alepidea

amatym

bica

Hexanee

xtractive

01m

gmL

Verapamil(10m

gkg)

Allextracts

crud

eand

purifi

edsho

wed

low

toxicityrang

ingfro

mLC

5005to

5ngmLapartfrom

AA4

andAA5

that

prod

uced

slightd

iarrheao

ndays

34and5andother

extractiv

esshow

edno

toxicityatad

oseo

f20

[24]

Evidence-Based Complementary and Alternative Medicine 9

stem rhizome and root exhibited activity against Candidaalbicans extracts and more than 50 mycotic inhibitionagainst fungal cultures [6] This study does not provide adose dependent evidence of the extract and negative controlwas not used in validating the traditional use of the plantas antifungal Also all the extracts except acetone extractshowed mycotic inhibition activity against Aspergillus flavusandAspergillus niger [8]These results validate the traditionaluses of the plant as an antifungal but no dose dependentevidencewas given in this study and positive control drugwasnot used in comparison with the extract used Therefore theantifungal activity of the extract cannot be compared with anantifungal drug

53 Antiviral Louvel et al [2] investigated the screeningactivity of the aerial part and root aqueous extract of Aamatymbica against a cell-based infection assay targeting thereplication of prototypic CXCR4-tropic (NL4-3) or CCR5-tropic (NL-AD87) HIV-1 strains designed to detect inhibitorsblocking any step of the viral life cycle The active ingredientidentified in the extract does not support a direct applicationof this plant extract for treating HIV infection The anti-HIV activity of the pure compound was found to be quitemoderate Lack of negative control and a dose dependentactivity of the extract make the antiviral activity of the extractinconclusive

54 Antihelminthes Research was undertaken using nema-tode growth agar with Caenorhabditis elegans var Bristol(N2)nematodes on the ethanol extract of the fresh and storedleaves and root ofA amatymbicaOnly fresh and storedwaterextracts showed a significant Anthelminthic [33] The resultof the study did not evaluate a dose dependent inhibitionof the extract against the worms even though the controlswere compared with the extract Further investigation isthus required to validate the use of the plant in traditionalmedicine as antihelmintic

55 Anti-Inflammatory The DCM PE water and EtOHrhizome extracts were evaluated using the enzyme basedcyclooxygenase assays COX-1 and COX-2 [6] The PE andDCM extracts had high COX-1 and COX-2 activities withpercentage inhibitions above 70 Ethanol extracts showedhigher inhibition (lt40) in COX-1 than COX-2 The waterextract on the other hand has a moderate inhibition activ-ity (40ndash60) in COX-1 and lowered in COX-2 (lt20)Despite reports on the undesirable effects of higher COX-1 inhibition as a result of its damage to the gastrointestinaltract [40] report of Mulaudzi et al [6] recorded a higherCOX-1 in both DCM and PE and a lower COX-1 inhibitionin ethanol and water The result favors the use of waterand ethanol as a solvent of extraction for this plant whenusing it against inflammation However conclusion cannotbe totally drawn on this report due to lack of negativecontrol and dosage Hence further investigation is required toprovide an evidence for its traditional use against inflamma-tion

56 Antihypertensive Hexane extractive (AA1) dichloro-methane extractive and methanol extractive of the fresh rhi-zome were investigated using purified compounds on bloodpressure and heart rate of anesthetizedWistar rats Moderatebut significant decrease in systolic blood pressure (SBP) andheart rate (HT) effects after intraperitoneal application onconscious rats was reported [24]

57 Antiplasmodium Dichloromethane (DCM) DCMmethanol (MeOH) (1 1) MeOH and purified water extractfrom the whole plant were investigated on plasmodialactivity and were found to contain plant based antimalarialagents showing promising antiplasmodial activity with IC

50

values of le10 gmL [34] This is the only study showing thedose dependent antiplasmodic activity of the plant extractin relation to the positive control Validation of the use ofthe plant in vivo is necessary to conclude the antiplasmodialactivity of A amatymbica

58 Diuretic The purified compounds of the fresh rhizomeextracted in hexaneethyl acetate of A amatymbica wereinvestigated using anesthetized Wistar rats The diuretic andnatriuretic effects of the extractives were found to be similarto the effects of chlorothiazide drug [24] The result suggeststhe inhibitory effect of the extractive of A amatymbica inreabsorption of K+ and Na+ ions suggesting the diureticand natriuretic effects of the extractives Lack of testedextractive in a dose dependent manner however negates thevalidation of the plants and the extractives for use as diuretictraditionally Further investigation is required to provideevidence for its use as a diuretic

6 Toxicological Reports

Four toxicity screens were identified in the literature Eachof the four screens tested uses crude aqueous and organicsolvents hexane extracts and extractives from the crudehexane extract and none of the reports recorded toxicity atall doses testedThe reported cytotoxicity of the fresh aqueousrhizome was investigated using HeLa Vero and Jurkat E61AA-2 or CEM-SS cells The extract was shown not to betoxic at all concentrations used in the test [35] since thedosage and controls were shown in this study in comparisonwith the control The second screens use bacterial cultures(100 120583L) in an Amen test assay which were added to 100120583L ofDCM PE water and EtOH rhizome plant extracts in 500120583Lphosphate buffer and 2mLof agar containing biotin-histidine(05mM) The Ames test revealed that none of the plantextracts significantly increased the number ofHis+ revertantswith respect to the negative control [6] The third test screenutilised the Brine Shrimp Lethal Assay (BSLA) Acute toxicityof the isolates from Alepidea amatymbica was screen againstbrine shrimp Artemia salina intersection bioassay The brineshrimp test showed that the crude hexane extracts have lowtoxicity with LC

5002 ngmL while the AA6 (wedelia seco-

kaurenolide) a derivative of A amatymbica has a low toxicityof 05 ngmL [24]The fourth screenmade use of Hippocratictest on rats with the use of hexane (AA1) extract and itrsquos

10 Evidence-Based Complementary and Alternative Medicine

extractives in dichloromethane and methanol (AA1) aftersubjection to repeated flash chromatography with gradientelution (100ndash70 hexaneEtOAc) to give AA3 a crystallinemixture of ent-kaur-en-19-oic acid ent-kaura-9 (11) 16-dien-19-oic acid and trachyloban-19-oic acid AA4 16-methoxy-ent-kaur-11-en-19-oic acid AA5 11-acetoxy-ent-kaur-16-en-19-oic acid and AA6 wedelia seco-kaurenolide All extractscrude and purified showed low toxicity ranging from 05 to5 ngmL (LC

50) apart from AA4 and AA5 that produced

slight diarrhea on days 3 4 and 5 and other extractivesshowed no toxicity at a dose of 20 [24] Apart from thestudies of Treurnicht [35] and Mulaudzi et al [6] mentionedabove the other studies do not provide sufficient evidencewith respect to the safety of A amatymbica considering theabsence of dosage used and control in their assays

7 Clinical Trials

To date there appears to be no published research indicatingthat extracts ofAlepidea amatymbica have undergone humanclinical trials

8 Conclusion

The review showed that A amatymbica has a widespread usein South Africa and other SADEC countriesThe recognitionof its ethnomedicinal usage for conditions of inflammationlike rheumatism and sore throat to usage for wounds coughasthma influenza diarrhea stomach cramps abdominal dis-orders malaria and diuretic is worth mentioningThe abilityof the extract to also restrain the growth of bacteria and fungiindicated its broad spectrum antimicrobial prospective Thepharmacological reports on A amatymbica revealed thera-peutic potential in the treatment of inflammation malariaand infectious diseases like influenza cough and diarrheaThe frequently occurring chemical constituents of Alepideaamatymbica belong to the kaurene-type diterpenoids andtheir derivatives Literature search onA amatymbica revealedthe use of cell line brine shrimps and rats for the determi-nation of the toxicity in the plant More investigations arenecessary to explore themedicinal potential of the plant in themanagement of rheumatism asthma hypertension diureticand inflammation Clinical trials and product development tofully exploit the medicinal value are also required to validateits folklore use in traditional medicine There is thereforethe need to develop the existing traditional use of this plantto amplify nutraceuticals product and commence clinicalresearch to exploit the plantrsquos novel phytochemicals

Conflict of Interests

The authors declare no conflict of interests

Acknowledgments

The authors are thankful to the Govan Mbeki Research andDevelopment Centre and the National Research Fund of theUniversity of Fort Hare South Africa

References

[1] B l Burtt ldquoUmbelliferae of southern Africa an introductionand annotated checklistrdquo Edinburgh Journal of Botany vol 48pp 133ndash282 1991

[2] S Louvel N Moodley I Seibert et al ldquoIdentification ofcompounds from the plant species Alepidea amatymbica activeagainst HIVrdquo South African Journal of Botany vol 86 pp 9ndash142013

[3] G Germishuizen N L Meyer Y Steenkamp and M KeithPlants of Southern Africa An Annotated Checklist vol 41 ofSABONET Report National Botanical Institute Pretoria SouthAfrica 2006

[4] R R Klopper P Lemmer and J Nel ldquoPteridophyta Pteridaceaecheilanthes deltoidea a new locality in Gauteng South AfricardquoBothalia vol 36 no 2 pp 173ndash174 2006

[5] Z Maksimovic S Dobric N Kovacevic and Z MilovanovicldquoDiuretic activity of Maydis stigma extract in ratsrdquo Pharmazievol 59 no 12 pp 967ndash971 2004

[6] R B Mulaudzi A R Ndhlala J F Finnie and J Van StadenldquoAntimicrobial anti-inflammatory and genotoxicity activityof Alepidea amatymbica and Alepidea natalensis (Apiaceae)rdquoSouth African Journal of Botany vol 75 no 3 pp 584ndash587 2009

[7] A de Castro and B-E van Wyk ldquoDiagnostic characters andgeographic distribution of Alepidea species used in traditionalmedicinerdquo South African Journal of Botany vol 60 no 6 pp345ndash350 1994

[8] A J Afolayan and F B Lewu ldquoAntimicrobial activity ofAlepideaamatymbicardquo Pharmaceutical Biology vol 47 no 5 pp 436ndash439 2009

[9] C Njume A A Jide and R N Ndip ldquoAqueous and organicsolvent-extracts of selected South African medicinal plantspossess antimicrobial activity against drug-resistant strainsof Helicobacter pylori inhibitory and bactericidal potentialrdquoInternational Journal of Molecular Sciences vol 12 no 9 pp5652ndash5665 2011

[10] J M Watt and M G Breyer-Brandwijik The Medicinal andPoisonous Plants of Southern and Eastern Africa E and SLivingstone London UK 2nd edition 1962

[11] B E van Wyk A de Castro P M Tilney P J D Winter andA R Magee ldquoA new species of Alepidea (Apiaceae subfamSaniculoideae)rdquo South African Journal of Botany vol 74 no 4pp 740ndash745 2008

[12] J T Mukinda and P F K Eagles ldquoThe South African Pharma-copoeia Monograph Projectrdquo Developed by South African Tra-ditional Medicines Research Group (SATMERG) and Schoolof Pharmacy University of the Western Cape (Unpublished)2010

[13] A Mapaura and J R Timberlake ldquoSouthern African plantred data listsrdquo Southern African Botanical Diversity Network(SABONET) Report 14 SABONET Pretoria South Africa

[14] A Maroyi ldquoEthnobotanical study of two threatened medicinalplants in Zimbabwerdquo International Journal of Biodiversity Sci-ence and Management vol 4 no 3 pp 148ndash153 2008

[15] S Talukdar ldquoLesothordquo in Southern African Plant Red Data ListsJ Golding Ed Southern African Botanical Diversity Network(SABONET) Report Number 14 pp 21ndash30 SABONET Preto-ria South Africa 2002

[16] R Scott-Shaw ldquoRare and threatened plants of KwaZulu-Nataland neighbouring regionsrdquo in A Plant Red Data Book p182 KwaZulu-Natal Nature Conservation Service Pietermar-itzburg South Africa 1999

Evidence-Based Complementary and Alternative Medicine 11

[17] The Plant List 2012 httpwwwtheplantlistorg[18] S Nonjinge and B B Tarr Natal National Botanical Garden

2013 httpwwwplantzafricacomplantabalipedeamathtm[19] M Gelfand S Mavi R B Drummond and B Ndemera The

Traditional Medical Practitioner in Zimbabwe Mambo PressGweru Zimbabwe 1985

[20] B E VanWyk and N Gericke rsquoPeoplersquos PlantsmdashA Guide toUseful Plants of South Africa Briza Publication Pretoria SouthAfrica 2000

[21] A Hutchings A H Scott G Lewis and A CunninghamZulu Medicinal Plants An Inventory University of Natal PressScottsville South Africa 1996

[22] B E van Wyk B van Oudtshoorn and N Gericke MedicinalPlants of South Africa Briza Publications Pretoria SouthAfrica 1997

[23] J A Guillarmod Flora of Lesotho J Cramer Lehre Germany1971

[24] L I Somova F O Shode K Moodley and Y GovenderldquoCardiovascular and diuretic activity of kaurene derivativesof Xylopia aethiopica and Alepidea amatymbicardquo Journal ofEthnopharmacology vol 77 no 2-3 pp 165ndash174 2001

[25] J Pujol NaturAfrica The Herbalists Handbook Jean PujolNatural Healers Foundation Durban South Africa 1990

[26] A Hutchings and J van Staden ldquoPlants used for stress-relatedailments in traditional Zulu Xhosa and Sotho medicine Part 1plants used for headachesrdquo Journal of Ethnopharmacology vol43 no 2 pp 89ndash124 1994

[27] A Hutchings ldquorsquoObservations on plant usage in Xhosa and Zulumedicinerdquo Bothalia vol 19 pp 225ndash235 1989

[28] J F Sobiecki ldquoA preliminary inventory of plants used forpsychoactive purposes in southern African healing traditionsrdquoTransactions of the Royal Society of SouthAfrica vol 57 pp 1ndash242002

[29] S O Bandeira F Gaspar and F P Pagula ldquoAfrican ethnobotanyand healthcare emphasis on Mozambiquerdquo PharmaceuticalBiology vol 39 pp 70ndash73 2001

[30] A Rustaiyan and A S Sadjadi ldquoKaurene derivatives fromAlepidea amatynsiardquo Phytochemistry vol 26 no 7 pp 2106ndash2107 1987

[31] C W Holzapfel B E van Wyk A de Castro W Marais andM Herbst ldquoA chemotaxonomic survey of kaurene derivativesin the genus Alepidea (Apiaceae)rdquo Biochemical Systematics andEcology vol 23 no 7-8 pp 799ndash803 1995

[32] D K Olivier B van Wyk and F R van Heerden ldquoThechemotaxonomic and medicinal significance of phenolic acidsin Arctopus and Alepidea (Apiaceae subfamily Saniculoideae)rdquoBiochemical Systematics and Ecology vol 36 no 9 pp 724ndash7292008

[33] G I Stafford A K Jager and J van Staden ldquoEffect ofstorage on the chemical composition and biological activityof several popular South African medicinal plantsrdquo Journal ofEthnopharmacology vol 97 no 1 pp 107ndash115 2005

[34] C Clarkson V JMaharaj N R Crouch et al ldquoIn vitro antiplas-modial activity of medicinal plants native to or naturalised inSouth Africardquo Journal of Ethnopharmacology vol 92 no 2-3pp 177ndash191 2004

[35] F T TreurnichtAn evaluation of the toxic and potential antiviraleffects of some plants used by South Africans for medicinalpurposes [MS thesis] University of Stellenbosch StellenboschSouth Africa 1997

[36] A Hutchings Zulu Medicinal Plants Natal University PressPietermaritzburg South Africa 1996

[37] C I Wright L van-Buren C I Kroner and M M GKoning ldquoHerbalmedicines as diuretics a reviewof the scientificevidencerdquo Journal of Ethnopharmacology vol 114 no 1 pp 1ndash312007

[38] F O Shode and B C Rogers ldquoThe chemistry of ApiaceaeIsolation and characterisation of diterpenoids and other ter-penoids from Alepidea amatymbicardquo in Proceedings of the 7thInternational Chemistry Conference in Africa Durban SouthAfrica 1998

[39] C W Fennell M E Light S G Sparg G I Stafford and JVan Staden ldquoAssessingAfricanmedicinal plants for efficacy andsafety agricultural and storage practicesrdquo Journal of Ethnophar-macology vol 95 no 2-3 pp 113ndash121 2004

[40] D Luseba E E Elgorashi D T Ntloedibe and J Van StadenldquoAntibacterial anti-inflammatory and mutagenic effects ofsome medicinal plants used in South Africa for the treatmentof wounds and retained placenta in livestockrdquo South AfricanJournal of Botany vol 73 no 3 pp 378ndash383 2007

Submit your manuscripts athttpwwwhindawicom

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MEDIATORSINFLAMMATION

of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Behavioural Neurology

EndocrinologyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Disease Markers

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

OncologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Oxidative Medicine and Cellular Longevity

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

PPAR Research

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

ObesityJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Computational and Mathematical Methods in Medicine

OphthalmologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Diabetes ResearchJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Research and TreatmentAIDS

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Gastroenterology Research and Practice

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Parkinsonrsquos Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom

Page 6: Review Article Alepidea amatymbica Eckl. & Zeyh.: A Review ...downloads.hindawi.com/journals/ecam/2014/284517.pdf · A Review of Its Traditional Uses, Phytochemistry, Pharmacology,

6 Evidence-Based Complementary and Alternative MedicineTa

ble3Con

tinued

Activ

ityteste

dMod

elused

Plantp

art

usedte

sted

material

Extracttype

Dosage

Con

trol

Results

Reference

Antim

icrobial

Agarw

elldiffu

sionmetho

dAlepidea

amatym

bica

were

investigated

against30

clinicalstrains

ofHpylori

Rootsrhizom

esEthylacetateacetone

ethano

lmethano

landwater

0002ndash50m

gmL

Referencec

ontro

lstrain

(NCT

C116

38)

Metronidazoleand

amoxicillin

wereincluded

aspo

sitivec

ontro

lantib

iotic

s

Methano

lwas

quantitatively

theb

est

solventfor

allthe

plants

whileethylacetatehadthe

lowestyieldsA

amatym

bica

gave

percentage

susceptib

ilitie

sof

lessthan

50

[9]

Antifu

ngal

Agard

ilutio

nmetho

dswith

thefollowingorganism

sAspergillus

flavus

Aspergillus

nigerand

Penicilliu

mnotatum

cultu

resw

erem

aintained

onPo

tato

Dextro

seagar

Crud

eextractso

ftheleafste

m

rhizom

eandroot

Aceton

eand

methano

l

Radialpatte

rnof

streakingof

organism

swas

used

Plates

containing

onlyPD

Aor

PDAwith

ther

espective

solvent

Diameter

ofthefun

gal

grow

thwas

measuredand

expressedas

percentage

grow

thinhibitio

nAllthe

extractsshow

edmorethan

50mycoticinhibitio

nwith

activ

ityrang

ingfro

m5139

to

8111at

5mgmLwith

ther

hizome

[8]

Antifu

ngal

Thea

ntifu

ngalactiv

ityof

thee

xtractsw

asevaluated

againstC

andida

albicans

(ATC

C10231)andfung

alcultu

rewas

prepared

inYeastM

alt(YM

)

Rhizom

eDCM

PE

waterand

EtOHrhizom

eextracts

01ndash50m

gmL

Water

andbacteriafre

ebroth(minusve)01m

gmL

neom

ycin

(+ve)

Allthee

xtractssho

wed

activ

ityagainstC

andida

albicans

[6]

Anti-infl

ammatory

Usin

gthee

nzym

ebased

cyclo

oxygenasea

ssays

COX-

1and

COX-

2Rh

izom

eDCM

PE

waterand

EtOHrhizom

eextracts

1mgmL

Water

andbacteriafre

ebroth(minusve)01m

gmL

neom

ycin

(+ve)

TheP

EandDCM

extracts

hadhigh

COX-

1activity

with

percentage

inhibitio

nsabove7

0E

thanol

extractshadinhibitio

nless

than

40

[6]

Antihypertensive

Purifi

edcompo

unds

onbloo

dpressure

andheart

rateof

anesthetized

Wistar

rats

Freshrhizom

es

Hexanee

xtractive

(AA1)

dichloromethane

extractiv

eand

methano

lextractive

ipinjectio

nof

sodium

thiopenton

e(40m

gkg

body

weight)

Chlorothiazide

Inadditio

nto

the

cardiovascular

effects

distinctdiureticand

natriuretic

effectswere

foun

d

[24]

Antiplasm

odium

Plasmodium

falciparum

strainD10

usingthe

parasitelactate

dehydrogenase(pL

DH)

assay

Who

leplant

Dichlorom

ethane

(DCM

)DCM

methano

l(M

eOH)(11)

MeO

Hand

purifi

edwater

100ndash

02120583

gmL)

Chloroqu

ined

ipho

sphate

served

asthep

ositive

control

Detectp

lant-based

antim

alarialagents

show

ingprom

ising

antip

lasm

odialactivity

with

IC50

values

ofle10gmL

[34]

Diuretic

TheL

ipschitztestwas

used

todeterm

inethe

Diuretic

andsaluretic

activ

ityin

rats

Freshrhizom

eHexaneethylacetate

extract

Thetestcom

poun

dwas

appliedorallyata

dose

of50

mgkg

Urea(

1gkgb

w)

Hydrochlorothiazide

(25m

gkg

bw)

Thed

iuretic

andnatriuretic

effectsof

thee

xtractives

werefou

ndto

besim

ilarto

thee

ffectso

fchlorothiazide

[24]

Evidence-Based Complementary and Alternative Medicine 7

Table3Con

tinued

Activ

ityteste

dMod

elused

Plantp

art

usedte

sted

material

Extracttype

Dosage

Con

trol

Results

Reference

Cardiovascular

Purifi

edcompo

unds

onbloo

dpressure

andheart

rateof

anesthetized

Wistar

rats

Purifi

edcompo

undfro

mfre

shrhizom

e

Hexanee

xtract

(AA1)

dichloromethaneand

methano

lportio

nof

AA1weres

ubjected

torepeated

flash

chromatograph

ywith

gradient

elutio

n(100ndash70

hexaneEtO

Ac)to

give

AA3a

crystalline

mixture

ofent-k

aur-en-19-oic

acident-kaura-9

(11)

16-dien-19-oicacid

and

trachyloban-19-oic

acidA

A4

16-m

etho

xy-ent-kaur-

11-en-19-oica

cid

AA511-a

cetoxy-ent-

kaur-16-en-19-oic

acidand

AA6

wedelia

seco-kaureno

lide

20mgkg

bw

intraperito

neally

Ethylene

glycol

Mod

eratebu

tsignificant

decreasin

gsysto

licbloo

dpressure

(SBP

)and

heart

rate(H

T)effectsaft

erintraperito

nealapplication

onconsciou

srats

[24]

Anti-H

IV

Extractsandtherein

subfractions

ofA

amatym

bica

werea

ssessed

inac

ellbased

assay

targetingther

eplicationof

prototypicCX

CR4-tro

pic

(NL4

-3)o

rCCR

5-tro

pic

(NL-AD87)H

IV-1str

ains

Aeria

lpartsand

roots

Aqueou

s500120583

Lof

samplea

taconcentrationof

25mgmL

Standard

retro

viral

inhibitor

Thea

ctiveing

redient

identifi

edin

thea

queous

extractd

oesn

otsupp

orta

directapplicationof

this

plantextractfortreating

HIV

infection

The

anti-HIV

activ

ityof

the

pure

compo

undwas

foun

dto

bequ

itemod

erate

[212]

Antihelminthes

Nem

atod

egrowth

agar

with

Caenorhabditiseleg

ans

varBristol(N

2)nematod

es

Freshandsto

red

leaves

androot

Ethano

l1m

gmL

Levamiso

le(+Ve

)and

nematod

eincub

ated

with

water

(minusVe

)

Onlyfre

shandsto

redwater

extractsshow

eda

significantantihelminthes

[33]

8 Evidence-Based Complementary and Alternative Medicine

Table3Con

tinued

Activ

ityteste

dMod

elused

Plantp

art

usedte

sted

material

Extracttype

Dosage

Con

trol

Results

Reference

Toxicity

Theb

acteria

lcultures

(100120583L)

werea

dded

to100120583

Lof

plantextractin

500120583

Lph

osph

ateb

uffer

and2m

Lof

agar

containing

biotin-histidine(05m

M)

Rhizom

eDCM

PE

waterand

EtOHrhizom

eextracts

50500and

5000120583gmL

4-Nitroq

uino

line-N-oxide

(4NQO)w

asused

asa

positivec

ontro

land

water

(minusve

control)

TheA

mes

testrevealed

that

none

ofthep

lant

extracts

significantly

increasedthe

numbero

fHis+

revertants

with

respecttothen

egative

control

[6]

Cytoxicity

HeLaVe

roJurkatE

61

AA-

2or

CEM-SScells

Freshrhizom

esAq

ueou

s1m

gmL

Not

stated

Thee

xtractwas

nottoxicat

anyconcentrationused

inthetest

[35]

Acutetoxicity

Evaluatio

nusingbrine

shrim

pAr

temiasalin

aintersectio

nbioassay

Freshrhizom

esHexane

Not

stated

Not

stated

Theb

rines

hrim

ptest

show

edthatthec

rude

hexane

extractshave

low

toxicitywith

LC5002

[24]

Toxicity

TheH

ippo

craticteston

rats

was

used

Freshrhizom

esIsolates

from

Alepidea

amatym

bica

Hexanee

xtractive

01m

gmL

Verapamil(10m

gkg)

Allextracts

crud

eand

purifi

edsho

wed

low

toxicityrang

ingfro

mLC

5005to

5ngmLapartfrom

AA4

andAA5

that

prod

uced

slightd

iarrheao

ndays

34and5andother

extractiv

esshow

edno

toxicityatad

oseo

f20

[24]

Evidence-Based Complementary and Alternative Medicine 9

stem rhizome and root exhibited activity against Candidaalbicans extracts and more than 50 mycotic inhibitionagainst fungal cultures [6] This study does not provide adose dependent evidence of the extract and negative controlwas not used in validating the traditional use of the plantas antifungal Also all the extracts except acetone extractshowed mycotic inhibition activity against Aspergillus flavusandAspergillus niger [8]These results validate the traditionaluses of the plant as an antifungal but no dose dependentevidencewas given in this study and positive control drugwasnot used in comparison with the extract used Therefore theantifungal activity of the extract cannot be compared with anantifungal drug

53 Antiviral Louvel et al [2] investigated the screeningactivity of the aerial part and root aqueous extract of Aamatymbica against a cell-based infection assay targeting thereplication of prototypic CXCR4-tropic (NL4-3) or CCR5-tropic (NL-AD87) HIV-1 strains designed to detect inhibitorsblocking any step of the viral life cycle The active ingredientidentified in the extract does not support a direct applicationof this plant extract for treating HIV infection The anti-HIV activity of the pure compound was found to be quitemoderate Lack of negative control and a dose dependentactivity of the extract make the antiviral activity of the extractinconclusive

54 Antihelminthes Research was undertaken using nema-tode growth agar with Caenorhabditis elegans var Bristol(N2)nematodes on the ethanol extract of the fresh and storedleaves and root ofA amatymbicaOnly fresh and storedwaterextracts showed a significant Anthelminthic [33] The resultof the study did not evaluate a dose dependent inhibitionof the extract against the worms even though the controlswere compared with the extract Further investigation isthus required to validate the use of the plant in traditionalmedicine as antihelmintic

55 Anti-Inflammatory The DCM PE water and EtOHrhizome extracts were evaluated using the enzyme basedcyclooxygenase assays COX-1 and COX-2 [6] The PE andDCM extracts had high COX-1 and COX-2 activities withpercentage inhibitions above 70 Ethanol extracts showedhigher inhibition (lt40) in COX-1 than COX-2 The waterextract on the other hand has a moderate inhibition activ-ity (40ndash60) in COX-1 and lowered in COX-2 (lt20)Despite reports on the undesirable effects of higher COX-1 inhibition as a result of its damage to the gastrointestinaltract [40] report of Mulaudzi et al [6] recorded a higherCOX-1 in both DCM and PE and a lower COX-1 inhibitionin ethanol and water The result favors the use of waterand ethanol as a solvent of extraction for this plant whenusing it against inflammation However conclusion cannotbe totally drawn on this report due to lack of negativecontrol and dosage Hence further investigation is required toprovide an evidence for its traditional use against inflamma-tion

56 Antihypertensive Hexane extractive (AA1) dichloro-methane extractive and methanol extractive of the fresh rhi-zome were investigated using purified compounds on bloodpressure and heart rate of anesthetizedWistar rats Moderatebut significant decrease in systolic blood pressure (SBP) andheart rate (HT) effects after intraperitoneal application onconscious rats was reported [24]

57 Antiplasmodium Dichloromethane (DCM) DCMmethanol (MeOH) (1 1) MeOH and purified water extractfrom the whole plant were investigated on plasmodialactivity and were found to contain plant based antimalarialagents showing promising antiplasmodial activity with IC

50

values of le10 gmL [34] This is the only study showing thedose dependent antiplasmodic activity of the plant extractin relation to the positive control Validation of the use ofthe plant in vivo is necessary to conclude the antiplasmodialactivity of A amatymbica

58 Diuretic The purified compounds of the fresh rhizomeextracted in hexaneethyl acetate of A amatymbica wereinvestigated using anesthetized Wistar rats The diuretic andnatriuretic effects of the extractives were found to be similarto the effects of chlorothiazide drug [24] The result suggeststhe inhibitory effect of the extractive of A amatymbica inreabsorption of K+ and Na+ ions suggesting the diureticand natriuretic effects of the extractives Lack of testedextractive in a dose dependent manner however negates thevalidation of the plants and the extractives for use as diuretictraditionally Further investigation is required to provideevidence for its use as a diuretic

6 Toxicological Reports

Four toxicity screens were identified in the literature Eachof the four screens tested uses crude aqueous and organicsolvents hexane extracts and extractives from the crudehexane extract and none of the reports recorded toxicity atall doses testedThe reported cytotoxicity of the fresh aqueousrhizome was investigated using HeLa Vero and Jurkat E61AA-2 or CEM-SS cells The extract was shown not to betoxic at all concentrations used in the test [35] since thedosage and controls were shown in this study in comparisonwith the control The second screens use bacterial cultures(100 120583L) in an Amen test assay which were added to 100120583L ofDCM PE water and EtOH rhizome plant extracts in 500120583Lphosphate buffer and 2mLof agar containing biotin-histidine(05mM) The Ames test revealed that none of the plantextracts significantly increased the number ofHis+ revertantswith respect to the negative control [6] The third test screenutilised the Brine Shrimp Lethal Assay (BSLA) Acute toxicityof the isolates from Alepidea amatymbica was screen againstbrine shrimp Artemia salina intersection bioassay The brineshrimp test showed that the crude hexane extracts have lowtoxicity with LC

5002 ngmL while the AA6 (wedelia seco-

kaurenolide) a derivative of A amatymbica has a low toxicityof 05 ngmL [24]The fourth screenmade use of Hippocratictest on rats with the use of hexane (AA1) extract and itrsquos

10 Evidence-Based Complementary and Alternative Medicine

extractives in dichloromethane and methanol (AA1) aftersubjection to repeated flash chromatography with gradientelution (100ndash70 hexaneEtOAc) to give AA3 a crystallinemixture of ent-kaur-en-19-oic acid ent-kaura-9 (11) 16-dien-19-oic acid and trachyloban-19-oic acid AA4 16-methoxy-ent-kaur-11-en-19-oic acid AA5 11-acetoxy-ent-kaur-16-en-19-oic acid and AA6 wedelia seco-kaurenolide All extractscrude and purified showed low toxicity ranging from 05 to5 ngmL (LC

50) apart from AA4 and AA5 that produced

slight diarrhea on days 3 4 and 5 and other extractivesshowed no toxicity at a dose of 20 [24] Apart from thestudies of Treurnicht [35] and Mulaudzi et al [6] mentionedabove the other studies do not provide sufficient evidencewith respect to the safety of A amatymbica considering theabsence of dosage used and control in their assays

7 Clinical Trials

To date there appears to be no published research indicatingthat extracts ofAlepidea amatymbica have undergone humanclinical trials

8 Conclusion

The review showed that A amatymbica has a widespread usein South Africa and other SADEC countriesThe recognitionof its ethnomedicinal usage for conditions of inflammationlike rheumatism and sore throat to usage for wounds coughasthma influenza diarrhea stomach cramps abdominal dis-orders malaria and diuretic is worth mentioningThe abilityof the extract to also restrain the growth of bacteria and fungiindicated its broad spectrum antimicrobial prospective Thepharmacological reports on A amatymbica revealed thera-peutic potential in the treatment of inflammation malariaand infectious diseases like influenza cough and diarrheaThe frequently occurring chemical constituents of Alepideaamatymbica belong to the kaurene-type diterpenoids andtheir derivatives Literature search onA amatymbica revealedthe use of cell line brine shrimps and rats for the determi-nation of the toxicity in the plant More investigations arenecessary to explore themedicinal potential of the plant in themanagement of rheumatism asthma hypertension diureticand inflammation Clinical trials and product development tofully exploit the medicinal value are also required to validateits folklore use in traditional medicine There is thereforethe need to develop the existing traditional use of this plantto amplify nutraceuticals product and commence clinicalresearch to exploit the plantrsquos novel phytochemicals

Conflict of Interests

The authors declare no conflict of interests

Acknowledgments

The authors are thankful to the Govan Mbeki Research andDevelopment Centre and the National Research Fund of theUniversity of Fort Hare South Africa

References

[1] B l Burtt ldquoUmbelliferae of southern Africa an introductionand annotated checklistrdquo Edinburgh Journal of Botany vol 48pp 133ndash282 1991

[2] S Louvel N Moodley I Seibert et al ldquoIdentification ofcompounds from the plant species Alepidea amatymbica activeagainst HIVrdquo South African Journal of Botany vol 86 pp 9ndash142013

[3] G Germishuizen N L Meyer Y Steenkamp and M KeithPlants of Southern Africa An Annotated Checklist vol 41 ofSABONET Report National Botanical Institute Pretoria SouthAfrica 2006

[4] R R Klopper P Lemmer and J Nel ldquoPteridophyta Pteridaceaecheilanthes deltoidea a new locality in Gauteng South AfricardquoBothalia vol 36 no 2 pp 173ndash174 2006

[5] Z Maksimovic S Dobric N Kovacevic and Z MilovanovicldquoDiuretic activity of Maydis stigma extract in ratsrdquo Pharmazievol 59 no 12 pp 967ndash971 2004

[6] R B Mulaudzi A R Ndhlala J F Finnie and J Van StadenldquoAntimicrobial anti-inflammatory and genotoxicity activityof Alepidea amatymbica and Alepidea natalensis (Apiaceae)rdquoSouth African Journal of Botany vol 75 no 3 pp 584ndash587 2009

[7] A de Castro and B-E van Wyk ldquoDiagnostic characters andgeographic distribution of Alepidea species used in traditionalmedicinerdquo South African Journal of Botany vol 60 no 6 pp345ndash350 1994

[8] A J Afolayan and F B Lewu ldquoAntimicrobial activity ofAlepideaamatymbicardquo Pharmaceutical Biology vol 47 no 5 pp 436ndash439 2009

[9] C Njume A A Jide and R N Ndip ldquoAqueous and organicsolvent-extracts of selected South African medicinal plantspossess antimicrobial activity against drug-resistant strainsof Helicobacter pylori inhibitory and bactericidal potentialrdquoInternational Journal of Molecular Sciences vol 12 no 9 pp5652ndash5665 2011

[10] J M Watt and M G Breyer-Brandwijik The Medicinal andPoisonous Plants of Southern and Eastern Africa E and SLivingstone London UK 2nd edition 1962

[11] B E van Wyk A de Castro P M Tilney P J D Winter andA R Magee ldquoA new species of Alepidea (Apiaceae subfamSaniculoideae)rdquo South African Journal of Botany vol 74 no 4pp 740ndash745 2008

[12] J T Mukinda and P F K Eagles ldquoThe South African Pharma-copoeia Monograph Projectrdquo Developed by South African Tra-ditional Medicines Research Group (SATMERG) and Schoolof Pharmacy University of the Western Cape (Unpublished)2010

[13] A Mapaura and J R Timberlake ldquoSouthern African plantred data listsrdquo Southern African Botanical Diversity Network(SABONET) Report 14 SABONET Pretoria South Africa

[14] A Maroyi ldquoEthnobotanical study of two threatened medicinalplants in Zimbabwerdquo International Journal of Biodiversity Sci-ence and Management vol 4 no 3 pp 148ndash153 2008

[15] S Talukdar ldquoLesothordquo in Southern African Plant Red Data ListsJ Golding Ed Southern African Botanical Diversity Network(SABONET) Report Number 14 pp 21ndash30 SABONET Preto-ria South Africa 2002

[16] R Scott-Shaw ldquoRare and threatened plants of KwaZulu-Nataland neighbouring regionsrdquo in A Plant Red Data Book p182 KwaZulu-Natal Nature Conservation Service Pietermar-itzburg South Africa 1999

Evidence-Based Complementary and Alternative Medicine 11

[17] The Plant List 2012 httpwwwtheplantlistorg[18] S Nonjinge and B B Tarr Natal National Botanical Garden

2013 httpwwwplantzafricacomplantabalipedeamathtm[19] M Gelfand S Mavi R B Drummond and B Ndemera The

Traditional Medical Practitioner in Zimbabwe Mambo PressGweru Zimbabwe 1985

[20] B E VanWyk and N Gericke rsquoPeoplersquos PlantsmdashA Guide toUseful Plants of South Africa Briza Publication Pretoria SouthAfrica 2000

[21] A Hutchings A H Scott G Lewis and A CunninghamZulu Medicinal Plants An Inventory University of Natal PressScottsville South Africa 1996

[22] B E van Wyk B van Oudtshoorn and N Gericke MedicinalPlants of South Africa Briza Publications Pretoria SouthAfrica 1997

[23] J A Guillarmod Flora of Lesotho J Cramer Lehre Germany1971

[24] L I Somova F O Shode K Moodley and Y GovenderldquoCardiovascular and diuretic activity of kaurene derivativesof Xylopia aethiopica and Alepidea amatymbicardquo Journal ofEthnopharmacology vol 77 no 2-3 pp 165ndash174 2001

[25] J Pujol NaturAfrica The Herbalists Handbook Jean PujolNatural Healers Foundation Durban South Africa 1990

[26] A Hutchings and J van Staden ldquoPlants used for stress-relatedailments in traditional Zulu Xhosa and Sotho medicine Part 1plants used for headachesrdquo Journal of Ethnopharmacology vol43 no 2 pp 89ndash124 1994

[27] A Hutchings ldquorsquoObservations on plant usage in Xhosa and Zulumedicinerdquo Bothalia vol 19 pp 225ndash235 1989

[28] J F Sobiecki ldquoA preliminary inventory of plants used forpsychoactive purposes in southern African healing traditionsrdquoTransactions of the Royal Society of SouthAfrica vol 57 pp 1ndash242002

[29] S O Bandeira F Gaspar and F P Pagula ldquoAfrican ethnobotanyand healthcare emphasis on Mozambiquerdquo PharmaceuticalBiology vol 39 pp 70ndash73 2001

[30] A Rustaiyan and A S Sadjadi ldquoKaurene derivatives fromAlepidea amatynsiardquo Phytochemistry vol 26 no 7 pp 2106ndash2107 1987

[31] C W Holzapfel B E van Wyk A de Castro W Marais andM Herbst ldquoA chemotaxonomic survey of kaurene derivativesin the genus Alepidea (Apiaceae)rdquo Biochemical Systematics andEcology vol 23 no 7-8 pp 799ndash803 1995

[32] D K Olivier B van Wyk and F R van Heerden ldquoThechemotaxonomic and medicinal significance of phenolic acidsin Arctopus and Alepidea (Apiaceae subfamily Saniculoideae)rdquoBiochemical Systematics and Ecology vol 36 no 9 pp 724ndash7292008

[33] G I Stafford A K Jager and J van Staden ldquoEffect ofstorage on the chemical composition and biological activityof several popular South African medicinal plantsrdquo Journal ofEthnopharmacology vol 97 no 1 pp 107ndash115 2005

[34] C Clarkson V JMaharaj N R Crouch et al ldquoIn vitro antiplas-modial activity of medicinal plants native to or naturalised inSouth Africardquo Journal of Ethnopharmacology vol 92 no 2-3pp 177ndash191 2004

[35] F T TreurnichtAn evaluation of the toxic and potential antiviraleffects of some plants used by South Africans for medicinalpurposes [MS thesis] University of Stellenbosch StellenboschSouth Africa 1997

[36] A Hutchings Zulu Medicinal Plants Natal University PressPietermaritzburg South Africa 1996

[37] C I Wright L van-Buren C I Kroner and M M GKoning ldquoHerbalmedicines as diuretics a reviewof the scientificevidencerdquo Journal of Ethnopharmacology vol 114 no 1 pp 1ndash312007

[38] F O Shode and B C Rogers ldquoThe chemistry of ApiaceaeIsolation and characterisation of diterpenoids and other ter-penoids from Alepidea amatymbicardquo in Proceedings of the 7thInternational Chemistry Conference in Africa Durban SouthAfrica 1998

[39] C W Fennell M E Light S G Sparg G I Stafford and JVan Staden ldquoAssessingAfricanmedicinal plants for efficacy andsafety agricultural and storage practicesrdquo Journal of Ethnophar-macology vol 95 no 2-3 pp 113ndash121 2004

[40] D Luseba E E Elgorashi D T Ntloedibe and J Van StadenldquoAntibacterial anti-inflammatory and mutagenic effects ofsome medicinal plants used in South Africa for the treatmentof wounds and retained placenta in livestockrdquo South AfricanJournal of Botany vol 73 no 3 pp 378ndash383 2007

Submit your manuscripts athttpwwwhindawicom

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MEDIATORSINFLAMMATION

of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Behavioural Neurology

EndocrinologyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Disease Markers

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

OncologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Oxidative Medicine and Cellular Longevity

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

PPAR Research

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

ObesityJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Computational and Mathematical Methods in Medicine

OphthalmologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Diabetes ResearchJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Research and TreatmentAIDS

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Gastroenterology Research and Practice

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Parkinsonrsquos Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom

Page 7: Review Article Alepidea amatymbica Eckl. & Zeyh.: A Review ...downloads.hindawi.com/journals/ecam/2014/284517.pdf · A Review of Its Traditional Uses, Phytochemistry, Pharmacology,

Evidence-Based Complementary and Alternative Medicine 7

Table3Con

tinued

Activ

ityteste

dMod

elused

Plantp

art

usedte

sted

material

Extracttype

Dosage

Con

trol

Results

Reference

Cardiovascular

Purifi

edcompo

unds

onbloo

dpressure

andheart

rateof

anesthetized

Wistar

rats

Purifi

edcompo

undfro

mfre

shrhizom

e

Hexanee

xtract

(AA1)

dichloromethaneand

methano

lportio

nof

AA1weres

ubjected

torepeated

flash

chromatograph

ywith

gradient

elutio

n(100ndash70

hexaneEtO

Ac)to

give

AA3a

crystalline

mixture

ofent-k

aur-en-19-oic

acident-kaura-9

(11)

16-dien-19-oicacid

and

trachyloban-19-oic

acidA

A4

16-m

etho

xy-ent-kaur-

11-en-19-oica

cid

AA511-a

cetoxy-ent-

kaur-16-en-19-oic

acidand

AA6

wedelia

seco-kaureno

lide

20mgkg

bw

intraperito

neally

Ethylene

glycol

Mod

eratebu

tsignificant

decreasin

gsysto

licbloo

dpressure

(SBP

)and

heart

rate(H

T)effectsaft

erintraperito

nealapplication

onconsciou

srats

[24]

Anti-H

IV

Extractsandtherein

subfractions

ofA

amatym

bica

werea

ssessed

inac

ellbased

assay

targetingther

eplicationof

prototypicCX

CR4-tro

pic

(NL4

-3)o

rCCR

5-tro

pic

(NL-AD87)H

IV-1str

ains

Aeria

lpartsand

roots

Aqueou

s500120583

Lof

samplea

taconcentrationof

25mgmL

Standard

retro

viral

inhibitor

Thea

ctiveing

redient

identifi

edin

thea

queous

extractd

oesn

otsupp

orta

directapplicationof

this

plantextractfortreating

HIV

infection

The

anti-HIV

activ

ityof

the

pure

compo

undwas

foun

dto

bequ

itemod

erate

[212]

Antihelminthes

Nem

atod

egrowth

agar

with

Caenorhabditiseleg

ans

varBristol(N

2)nematod

es

Freshandsto

red

leaves

androot

Ethano

l1m

gmL

Levamiso

le(+Ve

)and

nematod

eincub

ated

with

water

(minusVe

)

Onlyfre

shandsto

redwater

extractsshow

eda

significantantihelminthes

[33]

8 Evidence-Based Complementary and Alternative Medicine

Table3Con

tinued

Activ

ityteste

dMod

elused

Plantp

art

usedte

sted

material

Extracttype

Dosage

Con

trol

Results

Reference

Toxicity

Theb

acteria

lcultures

(100120583L)

werea

dded

to100120583

Lof

plantextractin

500120583

Lph

osph

ateb

uffer

and2m

Lof

agar

containing

biotin-histidine(05m

M)

Rhizom

eDCM

PE

waterand

EtOHrhizom

eextracts

50500and

5000120583gmL

4-Nitroq

uino

line-N-oxide

(4NQO)w

asused

asa

positivec

ontro

land

water

(minusve

control)

TheA

mes

testrevealed

that

none

ofthep

lant

extracts

significantly

increasedthe

numbero

fHis+

revertants

with

respecttothen

egative

control

[6]

Cytoxicity

HeLaVe

roJurkatE

61

AA-

2or

CEM-SScells

Freshrhizom

esAq

ueou

s1m

gmL

Not

stated

Thee

xtractwas

nottoxicat

anyconcentrationused

inthetest

[35]

Acutetoxicity

Evaluatio

nusingbrine

shrim

pAr

temiasalin

aintersectio

nbioassay

Freshrhizom

esHexane

Not

stated

Not

stated

Theb

rines

hrim

ptest

show

edthatthec

rude

hexane

extractshave

low

toxicitywith

LC5002

[24]

Toxicity

TheH

ippo

craticteston

rats

was

used

Freshrhizom

esIsolates

from

Alepidea

amatym

bica

Hexanee

xtractive

01m

gmL

Verapamil(10m

gkg)

Allextracts

crud

eand

purifi

edsho

wed

low

toxicityrang

ingfro

mLC

5005to

5ngmLapartfrom

AA4

andAA5

that

prod

uced

slightd

iarrheao

ndays

34and5andother

extractiv

esshow

edno

toxicityatad

oseo

f20

[24]

Evidence-Based Complementary and Alternative Medicine 9

stem rhizome and root exhibited activity against Candidaalbicans extracts and more than 50 mycotic inhibitionagainst fungal cultures [6] This study does not provide adose dependent evidence of the extract and negative controlwas not used in validating the traditional use of the plantas antifungal Also all the extracts except acetone extractshowed mycotic inhibition activity against Aspergillus flavusandAspergillus niger [8]These results validate the traditionaluses of the plant as an antifungal but no dose dependentevidencewas given in this study and positive control drugwasnot used in comparison with the extract used Therefore theantifungal activity of the extract cannot be compared with anantifungal drug

53 Antiviral Louvel et al [2] investigated the screeningactivity of the aerial part and root aqueous extract of Aamatymbica against a cell-based infection assay targeting thereplication of prototypic CXCR4-tropic (NL4-3) or CCR5-tropic (NL-AD87) HIV-1 strains designed to detect inhibitorsblocking any step of the viral life cycle The active ingredientidentified in the extract does not support a direct applicationof this plant extract for treating HIV infection The anti-HIV activity of the pure compound was found to be quitemoderate Lack of negative control and a dose dependentactivity of the extract make the antiviral activity of the extractinconclusive

54 Antihelminthes Research was undertaken using nema-tode growth agar with Caenorhabditis elegans var Bristol(N2)nematodes on the ethanol extract of the fresh and storedleaves and root ofA amatymbicaOnly fresh and storedwaterextracts showed a significant Anthelminthic [33] The resultof the study did not evaluate a dose dependent inhibitionof the extract against the worms even though the controlswere compared with the extract Further investigation isthus required to validate the use of the plant in traditionalmedicine as antihelmintic

55 Anti-Inflammatory The DCM PE water and EtOHrhizome extracts were evaluated using the enzyme basedcyclooxygenase assays COX-1 and COX-2 [6] The PE andDCM extracts had high COX-1 and COX-2 activities withpercentage inhibitions above 70 Ethanol extracts showedhigher inhibition (lt40) in COX-1 than COX-2 The waterextract on the other hand has a moderate inhibition activ-ity (40ndash60) in COX-1 and lowered in COX-2 (lt20)Despite reports on the undesirable effects of higher COX-1 inhibition as a result of its damage to the gastrointestinaltract [40] report of Mulaudzi et al [6] recorded a higherCOX-1 in both DCM and PE and a lower COX-1 inhibitionin ethanol and water The result favors the use of waterand ethanol as a solvent of extraction for this plant whenusing it against inflammation However conclusion cannotbe totally drawn on this report due to lack of negativecontrol and dosage Hence further investigation is required toprovide an evidence for its traditional use against inflamma-tion

56 Antihypertensive Hexane extractive (AA1) dichloro-methane extractive and methanol extractive of the fresh rhi-zome were investigated using purified compounds on bloodpressure and heart rate of anesthetizedWistar rats Moderatebut significant decrease in systolic blood pressure (SBP) andheart rate (HT) effects after intraperitoneal application onconscious rats was reported [24]

57 Antiplasmodium Dichloromethane (DCM) DCMmethanol (MeOH) (1 1) MeOH and purified water extractfrom the whole plant were investigated on plasmodialactivity and were found to contain plant based antimalarialagents showing promising antiplasmodial activity with IC

50

values of le10 gmL [34] This is the only study showing thedose dependent antiplasmodic activity of the plant extractin relation to the positive control Validation of the use ofthe plant in vivo is necessary to conclude the antiplasmodialactivity of A amatymbica

58 Diuretic The purified compounds of the fresh rhizomeextracted in hexaneethyl acetate of A amatymbica wereinvestigated using anesthetized Wistar rats The diuretic andnatriuretic effects of the extractives were found to be similarto the effects of chlorothiazide drug [24] The result suggeststhe inhibitory effect of the extractive of A amatymbica inreabsorption of K+ and Na+ ions suggesting the diureticand natriuretic effects of the extractives Lack of testedextractive in a dose dependent manner however negates thevalidation of the plants and the extractives for use as diuretictraditionally Further investigation is required to provideevidence for its use as a diuretic

6 Toxicological Reports

Four toxicity screens were identified in the literature Eachof the four screens tested uses crude aqueous and organicsolvents hexane extracts and extractives from the crudehexane extract and none of the reports recorded toxicity atall doses testedThe reported cytotoxicity of the fresh aqueousrhizome was investigated using HeLa Vero and Jurkat E61AA-2 or CEM-SS cells The extract was shown not to betoxic at all concentrations used in the test [35] since thedosage and controls were shown in this study in comparisonwith the control The second screens use bacterial cultures(100 120583L) in an Amen test assay which were added to 100120583L ofDCM PE water and EtOH rhizome plant extracts in 500120583Lphosphate buffer and 2mLof agar containing biotin-histidine(05mM) The Ames test revealed that none of the plantextracts significantly increased the number ofHis+ revertantswith respect to the negative control [6] The third test screenutilised the Brine Shrimp Lethal Assay (BSLA) Acute toxicityof the isolates from Alepidea amatymbica was screen againstbrine shrimp Artemia salina intersection bioassay The brineshrimp test showed that the crude hexane extracts have lowtoxicity with LC

5002 ngmL while the AA6 (wedelia seco-

kaurenolide) a derivative of A amatymbica has a low toxicityof 05 ngmL [24]The fourth screenmade use of Hippocratictest on rats with the use of hexane (AA1) extract and itrsquos

10 Evidence-Based Complementary and Alternative Medicine

extractives in dichloromethane and methanol (AA1) aftersubjection to repeated flash chromatography with gradientelution (100ndash70 hexaneEtOAc) to give AA3 a crystallinemixture of ent-kaur-en-19-oic acid ent-kaura-9 (11) 16-dien-19-oic acid and trachyloban-19-oic acid AA4 16-methoxy-ent-kaur-11-en-19-oic acid AA5 11-acetoxy-ent-kaur-16-en-19-oic acid and AA6 wedelia seco-kaurenolide All extractscrude and purified showed low toxicity ranging from 05 to5 ngmL (LC

50) apart from AA4 and AA5 that produced

slight diarrhea on days 3 4 and 5 and other extractivesshowed no toxicity at a dose of 20 [24] Apart from thestudies of Treurnicht [35] and Mulaudzi et al [6] mentionedabove the other studies do not provide sufficient evidencewith respect to the safety of A amatymbica considering theabsence of dosage used and control in their assays

7 Clinical Trials

To date there appears to be no published research indicatingthat extracts ofAlepidea amatymbica have undergone humanclinical trials

8 Conclusion

The review showed that A amatymbica has a widespread usein South Africa and other SADEC countriesThe recognitionof its ethnomedicinal usage for conditions of inflammationlike rheumatism and sore throat to usage for wounds coughasthma influenza diarrhea stomach cramps abdominal dis-orders malaria and diuretic is worth mentioningThe abilityof the extract to also restrain the growth of bacteria and fungiindicated its broad spectrum antimicrobial prospective Thepharmacological reports on A amatymbica revealed thera-peutic potential in the treatment of inflammation malariaand infectious diseases like influenza cough and diarrheaThe frequently occurring chemical constituents of Alepideaamatymbica belong to the kaurene-type diterpenoids andtheir derivatives Literature search onA amatymbica revealedthe use of cell line brine shrimps and rats for the determi-nation of the toxicity in the plant More investigations arenecessary to explore themedicinal potential of the plant in themanagement of rheumatism asthma hypertension diureticand inflammation Clinical trials and product development tofully exploit the medicinal value are also required to validateits folklore use in traditional medicine There is thereforethe need to develop the existing traditional use of this plantto amplify nutraceuticals product and commence clinicalresearch to exploit the plantrsquos novel phytochemicals

Conflict of Interests

The authors declare no conflict of interests

Acknowledgments

The authors are thankful to the Govan Mbeki Research andDevelopment Centre and the National Research Fund of theUniversity of Fort Hare South Africa

References

[1] B l Burtt ldquoUmbelliferae of southern Africa an introductionand annotated checklistrdquo Edinburgh Journal of Botany vol 48pp 133ndash282 1991

[2] S Louvel N Moodley I Seibert et al ldquoIdentification ofcompounds from the plant species Alepidea amatymbica activeagainst HIVrdquo South African Journal of Botany vol 86 pp 9ndash142013

[3] G Germishuizen N L Meyer Y Steenkamp and M KeithPlants of Southern Africa An Annotated Checklist vol 41 ofSABONET Report National Botanical Institute Pretoria SouthAfrica 2006

[4] R R Klopper P Lemmer and J Nel ldquoPteridophyta Pteridaceaecheilanthes deltoidea a new locality in Gauteng South AfricardquoBothalia vol 36 no 2 pp 173ndash174 2006

[5] Z Maksimovic S Dobric N Kovacevic and Z MilovanovicldquoDiuretic activity of Maydis stigma extract in ratsrdquo Pharmazievol 59 no 12 pp 967ndash971 2004

[6] R B Mulaudzi A R Ndhlala J F Finnie and J Van StadenldquoAntimicrobial anti-inflammatory and genotoxicity activityof Alepidea amatymbica and Alepidea natalensis (Apiaceae)rdquoSouth African Journal of Botany vol 75 no 3 pp 584ndash587 2009

[7] A de Castro and B-E van Wyk ldquoDiagnostic characters andgeographic distribution of Alepidea species used in traditionalmedicinerdquo South African Journal of Botany vol 60 no 6 pp345ndash350 1994

[8] A J Afolayan and F B Lewu ldquoAntimicrobial activity ofAlepideaamatymbicardquo Pharmaceutical Biology vol 47 no 5 pp 436ndash439 2009

[9] C Njume A A Jide and R N Ndip ldquoAqueous and organicsolvent-extracts of selected South African medicinal plantspossess antimicrobial activity against drug-resistant strainsof Helicobacter pylori inhibitory and bactericidal potentialrdquoInternational Journal of Molecular Sciences vol 12 no 9 pp5652ndash5665 2011

[10] J M Watt and M G Breyer-Brandwijik The Medicinal andPoisonous Plants of Southern and Eastern Africa E and SLivingstone London UK 2nd edition 1962

[11] B E van Wyk A de Castro P M Tilney P J D Winter andA R Magee ldquoA new species of Alepidea (Apiaceae subfamSaniculoideae)rdquo South African Journal of Botany vol 74 no 4pp 740ndash745 2008

[12] J T Mukinda and P F K Eagles ldquoThe South African Pharma-copoeia Monograph Projectrdquo Developed by South African Tra-ditional Medicines Research Group (SATMERG) and Schoolof Pharmacy University of the Western Cape (Unpublished)2010

[13] A Mapaura and J R Timberlake ldquoSouthern African plantred data listsrdquo Southern African Botanical Diversity Network(SABONET) Report 14 SABONET Pretoria South Africa

[14] A Maroyi ldquoEthnobotanical study of two threatened medicinalplants in Zimbabwerdquo International Journal of Biodiversity Sci-ence and Management vol 4 no 3 pp 148ndash153 2008

[15] S Talukdar ldquoLesothordquo in Southern African Plant Red Data ListsJ Golding Ed Southern African Botanical Diversity Network(SABONET) Report Number 14 pp 21ndash30 SABONET Preto-ria South Africa 2002

[16] R Scott-Shaw ldquoRare and threatened plants of KwaZulu-Nataland neighbouring regionsrdquo in A Plant Red Data Book p182 KwaZulu-Natal Nature Conservation Service Pietermar-itzburg South Africa 1999

Evidence-Based Complementary and Alternative Medicine 11

[17] The Plant List 2012 httpwwwtheplantlistorg[18] S Nonjinge and B B Tarr Natal National Botanical Garden

2013 httpwwwplantzafricacomplantabalipedeamathtm[19] M Gelfand S Mavi R B Drummond and B Ndemera The

Traditional Medical Practitioner in Zimbabwe Mambo PressGweru Zimbabwe 1985

[20] B E VanWyk and N Gericke rsquoPeoplersquos PlantsmdashA Guide toUseful Plants of South Africa Briza Publication Pretoria SouthAfrica 2000

[21] A Hutchings A H Scott G Lewis and A CunninghamZulu Medicinal Plants An Inventory University of Natal PressScottsville South Africa 1996

[22] B E van Wyk B van Oudtshoorn and N Gericke MedicinalPlants of South Africa Briza Publications Pretoria SouthAfrica 1997

[23] J A Guillarmod Flora of Lesotho J Cramer Lehre Germany1971

[24] L I Somova F O Shode K Moodley and Y GovenderldquoCardiovascular and diuretic activity of kaurene derivativesof Xylopia aethiopica and Alepidea amatymbicardquo Journal ofEthnopharmacology vol 77 no 2-3 pp 165ndash174 2001

[25] J Pujol NaturAfrica The Herbalists Handbook Jean PujolNatural Healers Foundation Durban South Africa 1990

[26] A Hutchings and J van Staden ldquoPlants used for stress-relatedailments in traditional Zulu Xhosa and Sotho medicine Part 1plants used for headachesrdquo Journal of Ethnopharmacology vol43 no 2 pp 89ndash124 1994

[27] A Hutchings ldquorsquoObservations on plant usage in Xhosa and Zulumedicinerdquo Bothalia vol 19 pp 225ndash235 1989

[28] J F Sobiecki ldquoA preliminary inventory of plants used forpsychoactive purposes in southern African healing traditionsrdquoTransactions of the Royal Society of SouthAfrica vol 57 pp 1ndash242002

[29] S O Bandeira F Gaspar and F P Pagula ldquoAfrican ethnobotanyand healthcare emphasis on Mozambiquerdquo PharmaceuticalBiology vol 39 pp 70ndash73 2001

[30] A Rustaiyan and A S Sadjadi ldquoKaurene derivatives fromAlepidea amatynsiardquo Phytochemistry vol 26 no 7 pp 2106ndash2107 1987

[31] C W Holzapfel B E van Wyk A de Castro W Marais andM Herbst ldquoA chemotaxonomic survey of kaurene derivativesin the genus Alepidea (Apiaceae)rdquo Biochemical Systematics andEcology vol 23 no 7-8 pp 799ndash803 1995

[32] D K Olivier B van Wyk and F R van Heerden ldquoThechemotaxonomic and medicinal significance of phenolic acidsin Arctopus and Alepidea (Apiaceae subfamily Saniculoideae)rdquoBiochemical Systematics and Ecology vol 36 no 9 pp 724ndash7292008

[33] G I Stafford A K Jager and J van Staden ldquoEffect ofstorage on the chemical composition and biological activityof several popular South African medicinal plantsrdquo Journal ofEthnopharmacology vol 97 no 1 pp 107ndash115 2005

[34] C Clarkson V JMaharaj N R Crouch et al ldquoIn vitro antiplas-modial activity of medicinal plants native to or naturalised inSouth Africardquo Journal of Ethnopharmacology vol 92 no 2-3pp 177ndash191 2004

[35] F T TreurnichtAn evaluation of the toxic and potential antiviraleffects of some plants used by South Africans for medicinalpurposes [MS thesis] University of Stellenbosch StellenboschSouth Africa 1997

[36] A Hutchings Zulu Medicinal Plants Natal University PressPietermaritzburg South Africa 1996

[37] C I Wright L van-Buren C I Kroner and M M GKoning ldquoHerbalmedicines as diuretics a reviewof the scientificevidencerdquo Journal of Ethnopharmacology vol 114 no 1 pp 1ndash312007

[38] F O Shode and B C Rogers ldquoThe chemistry of ApiaceaeIsolation and characterisation of diterpenoids and other ter-penoids from Alepidea amatymbicardquo in Proceedings of the 7thInternational Chemistry Conference in Africa Durban SouthAfrica 1998

[39] C W Fennell M E Light S G Sparg G I Stafford and JVan Staden ldquoAssessingAfricanmedicinal plants for efficacy andsafety agricultural and storage practicesrdquo Journal of Ethnophar-macology vol 95 no 2-3 pp 113ndash121 2004

[40] D Luseba E E Elgorashi D T Ntloedibe and J Van StadenldquoAntibacterial anti-inflammatory and mutagenic effects ofsome medicinal plants used in South Africa for the treatmentof wounds and retained placenta in livestockrdquo South AfricanJournal of Botany vol 73 no 3 pp 378ndash383 2007

Submit your manuscripts athttpwwwhindawicom

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MEDIATORSINFLAMMATION

of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Behavioural Neurology

EndocrinologyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Disease Markers

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

OncologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Oxidative Medicine and Cellular Longevity

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

PPAR Research

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

ObesityJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Computational and Mathematical Methods in Medicine

OphthalmologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Diabetes ResearchJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Research and TreatmentAIDS

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Gastroenterology Research and Practice

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Parkinsonrsquos Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom

Page 8: Review Article Alepidea amatymbica Eckl. & Zeyh.: A Review ...downloads.hindawi.com/journals/ecam/2014/284517.pdf · A Review of Its Traditional Uses, Phytochemistry, Pharmacology,

8 Evidence-Based Complementary and Alternative Medicine

Table3Con

tinued

Activ

ityteste

dMod

elused

Plantp

art

usedte

sted

material

Extracttype

Dosage

Con

trol

Results

Reference

Toxicity

Theb

acteria

lcultures

(100120583L)

werea

dded

to100120583

Lof

plantextractin

500120583

Lph

osph

ateb

uffer

and2m

Lof

agar

containing

biotin-histidine(05m

M)

Rhizom

eDCM

PE

waterand

EtOHrhizom

eextracts

50500and

5000120583gmL

4-Nitroq

uino

line-N-oxide

(4NQO)w

asused

asa

positivec

ontro

land

water

(minusve

control)

TheA

mes

testrevealed

that

none

ofthep

lant

extracts

significantly

increasedthe

numbero

fHis+

revertants

with

respecttothen

egative

control

[6]

Cytoxicity

HeLaVe

roJurkatE

61

AA-

2or

CEM-SScells

Freshrhizom

esAq

ueou

s1m

gmL

Not

stated

Thee

xtractwas

nottoxicat

anyconcentrationused

inthetest

[35]

Acutetoxicity

Evaluatio

nusingbrine

shrim

pAr

temiasalin

aintersectio

nbioassay

Freshrhizom

esHexane

Not

stated

Not

stated

Theb

rines

hrim

ptest

show

edthatthec

rude

hexane

extractshave

low

toxicitywith

LC5002

[24]

Toxicity

TheH

ippo

craticteston

rats

was

used

Freshrhizom

esIsolates

from

Alepidea

amatym

bica

Hexanee

xtractive

01m

gmL

Verapamil(10m

gkg)

Allextracts

crud

eand

purifi

edsho

wed

low

toxicityrang

ingfro

mLC

5005to

5ngmLapartfrom

AA4

andAA5

that

prod

uced

slightd

iarrheao

ndays

34and5andother

extractiv

esshow

edno

toxicityatad

oseo

f20

[24]

Evidence-Based Complementary and Alternative Medicine 9

stem rhizome and root exhibited activity against Candidaalbicans extracts and more than 50 mycotic inhibitionagainst fungal cultures [6] This study does not provide adose dependent evidence of the extract and negative controlwas not used in validating the traditional use of the plantas antifungal Also all the extracts except acetone extractshowed mycotic inhibition activity against Aspergillus flavusandAspergillus niger [8]These results validate the traditionaluses of the plant as an antifungal but no dose dependentevidencewas given in this study and positive control drugwasnot used in comparison with the extract used Therefore theantifungal activity of the extract cannot be compared with anantifungal drug

53 Antiviral Louvel et al [2] investigated the screeningactivity of the aerial part and root aqueous extract of Aamatymbica against a cell-based infection assay targeting thereplication of prototypic CXCR4-tropic (NL4-3) or CCR5-tropic (NL-AD87) HIV-1 strains designed to detect inhibitorsblocking any step of the viral life cycle The active ingredientidentified in the extract does not support a direct applicationof this plant extract for treating HIV infection The anti-HIV activity of the pure compound was found to be quitemoderate Lack of negative control and a dose dependentactivity of the extract make the antiviral activity of the extractinconclusive

54 Antihelminthes Research was undertaken using nema-tode growth agar with Caenorhabditis elegans var Bristol(N2)nematodes on the ethanol extract of the fresh and storedleaves and root ofA amatymbicaOnly fresh and storedwaterextracts showed a significant Anthelminthic [33] The resultof the study did not evaluate a dose dependent inhibitionof the extract against the worms even though the controlswere compared with the extract Further investigation isthus required to validate the use of the plant in traditionalmedicine as antihelmintic

55 Anti-Inflammatory The DCM PE water and EtOHrhizome extracts were evaluated using the enzyme basedcyclooxygenase assays COX-1 and COX-2 [6] The PE andDCM extracts had high COX-1 and COX-2 activities withpercentage inhibitions above 70 Ethanol extracts showedhigher inhibition (lt40) in COX-1 than COX-2 The waterextract on the other hand has a moderate inhibition activ-ity (40ndash60) in COX-1 and lowered in COX-2 (lt20)Despite reports on the undesirable effects of higher COX-1 inhibition as a result of its damage to the gastrointestinaltract [40] report of Mulaudzi et al [6] recorded a higherCOX-1 in both DCM and PE and a lower COX-1 inhibitionin ethanol and water The result favors the use of waterand ethanol as a solvent of extraction for this plant whenusing it against inflammation However conclusion cannotbe totally drawn on this report due to lack of negativecontrol and dosage Hence further investigation is required toprovide an evidence for its traditional use against inflamma-tion

56 Antihypertensive Hexane extractive (AA1) dichloro-methane extractive and methanol extractive of the fresh rhi-zome were investigated using purified compounds on bloodpressure and heart rate of anesthetizedWistar rats Moderatebut significant decrease in systolic blood pressure (SBP) andheart rate (HT) effects after intraperitoneal application onconscious rats was reported [24]

57 Antiplasmodium Dichloromethane (DCM) DCMmethanol (MeOH) (1 1) MeOH and purified water extractfrom the whole plant were investigated on plasmodialactivity and were found to contain plant based antimalarialagents showing promising antiplasmodial activity with IC

50

values of le10 gmL [34] This is the only study showing thedose dependent antiplasmodic activity of the plant extractin relation to the positive control Validation of the use ofthe plant in vivo is necessary to conclude the antiplasmodialactivity of A amatymbica

58 Diuretic The purified compounds of the fresh rhizomeextracted in hexaneethyl acetate of A amatymbica wereinvestigated using anesthetized Wistar rats The diuretic andnatriuretic effects of the extractives were found to be similarto the effects of chlorothiazide drug [24] The result suggeststhe inhibitory effect of the extractive of A amatymbica inreabsorption of K+ and Na+ ions suggesting the diureticand natriuretic effects of the extractives Lack of testedextractive in a dose dependent manner however negates thevalidation of the plants and the extractives for use as diuretictraditionally Further investigation is required to provideevidence for its use as a diuretic

6 Toxicological Reports

Four toxicity screens were identified in the literature Eachof the four screens tested uses crude aqueous and organicsolvents hexane extracts and extractives from the crudehexane extract and none of the reports recorded toxicity atall doses testedThe reported cytotoxicity of the fresh aqueousrhizome was investigated using HeLa Vero and Jurkat E61AA-2 or CEM-SS cells The extract was shown not to betoxic at all concentrations used in the test [35] since thedosage and controls were shown in this study in comparisonwith the control The second screens use bacterial cultures(100 120583L) in an Amen test assay which were added to 100120583L ofDCM PE water and EtOH rhizome plant extracts in 500120583Lphosphate buffer and 2mLof agar containing biotin-histidine(05mM) The Ames test revealed that none of the plantextracts significantly increased the number ofHis+ revertantswith respect to the negative control [6] The third test screenutilised the Brine Shrimp Lethal Assay (BSLA) Acute toxicityof the isolates from Alepidea amatymbica was screen againstbrine shrimp Artemia salina intersection bioassay The brineshrimp test showed that the crude hexane extracts have lowtoxicity with LC

5002 ngmL while the AA6 (wedelia seco-

kaurenolide) a derivative of A amatymbica has a low toxicityof 05 ngmL [24]The fourth screenmade use of Hippocratictest on rats with the use of hexane (AA1) extract and itrsquos

10 Evidence-Based Complementary and Alternative Medicine

extractives in dichloromethane and methanol (AA1) aftersubjection to repeated flash chromatography with gradientelution (100ndash70 hexaneEtOAc) to give AA3 a crystallinemixture of ent-kaur-en-19-oic acid ent-kaura-9 (11) 16-dien-19-oic acid and trachyloban-19-oic acid AA4 16-methoxy-ent-kaur-11-en-19-oic acid AA5 11-acetoxy-ent-kaur-16-en-19-oic acid and AA6 wedelia seco-kaurenolide All extractscrude and purified showed low toxicity ranging from 05 to5 ngmL (LC

50) apart from AA4 and AA5 that produced

slight diarrhea on days 3 4 and 5 and other extractivesshowed no toxicity at a dose of 20 [24] Apart from thestudies of Treurnicht [35] and Mulaudzi et al [6] mentionedabove the other studies do not provide sufficient evidencewith respect to the safety of A amatymbica considering theabsence of dosage used and control in their assays

7 Clinical Trials

To date there appears to be no published research indicatingthat extracts ofAlepidea amatymbica have undergone humanclinical trials

8 Conclusion

The review showed that A amatymbica has a widespread usein South Africa and other SADEC countriesThe recognitionof its ethnomedicinal usage for conditions of inflammationlike rheumatism and sore throat to usage for wounds coughasthma influenza diarrhea stomach cramps abdominal dis-orders malaria and diuretic is worth mentioningThe abilityof the extract to also restrain the growth of bacteria and fungiindicated its broad spectrum antimicrobial prospective Thepharmacological reports on A amatymbica revealed thera-peutic potential in the treatment of inflammation malariaand infectious diseases like influenza cough and diarrheaThe frequently occurring chemical constituents of Alepideaamatymbica belong to the kaurene-type diterpenoids andtheir derivatives Literature search onA amatymbica revealedthe use of cell line brine shrimps and rats for the determi-nation of the toxicity in the plant More investigations arenecessary to explore themedicinal potential of the plant in themanagement of rheumatism asthma hypertension diureticand inflammation Clinical trials and product development tofully exploit the medicinal value are also required to validateits folklore use in traditional medicine There is thereforethe need to develop the existing traditional use of this plantto amplify nutraceuticals product and commence clinicalresearch to exploit the plantrsquos novel phytochemicals

Conflict of Interests

The authors declare no conflict of interests

Acknowledgments

The authors are thankful to the Govan Mbeki Research andDevelopment Centre and the National Research Fund of theUniversity of Fort Hare South Africa

References

[1] B l Burtt ldquoUmbelliferae of southern Africa an introductionand annotated checklistrdquo Edinburgh Journal of Botany vol 48pp 133ndash282 1991

[2] S Louvel N Moodley I Seibert et al ldquoIdentification ofcompounds from the plant species Alepidea amatymbica activeagainst HIVrdquo South African Journal of Botany vol 86 pp 9ndash142013

[3] G Germishuizen N L Meyer Y Steenkamp and M KeithPlants of Southern Africa An Annotated Checklist vol 41 ofSABONET Report National Botanical Institute Pretoria SouthAfrica 2006

[4] R R Klopper P Lemmer and J Nel ldquoPteridophyta Pteridaceaecheilanthes deltoidea a new locality in Gauteng South AfricardquoBothalia vol 36 no 2 pp 173ndash174 2006

[5] Z Maksimovic S Dobric N Kovacevic and Z MilovanovicldquoDiuretic activity of Maydis stigma extract in ratsrdquo Pharmazievol 59 no 12 pp 967ndash971 2004

[6] R B Mulaudzi A R Ndhlala J F Finnie and J Van StadenldquoAntimicrobial anti-inflammatory and genotoxicity activityof Alepidea amatymbica and Alepidea natalensis (Apiaceae)rdquoSouth African Journal of Botany vol 75 no 3 pp 584ndash587 2009

[7] A de Castro and B-E van Wyk ldquoDiagnostic characters andgeographic distribution of Alepidea species used in traditionalmedicinerdquo South African Journal of Botany vol 60 no 6 pp345ndash350 1994

[8] A J Afolayan and F B Lewu ldquoAntimicrobial activity ofAlepideaamatymbicardquo Pharmaceutical Biology vol 47 no 5 pp 436ndash439 2009

[9] C Njume A A Jide and R N Ndip ldquoAqueous and organicsolvent-extracts of selected South African medicinal plantspossess antimicrobial activity against drug-resistant strainsof Helicobacter pylori inhibitory and bactericidal potentialrdquoInternational Journal of Molecular Sciences vol 12 no 9 pp5652ndash5665 2011

[10] J M Watt and M G Breyer-Brandwijik The Medicinal andPoisonous Plants of Southern and Eastern Africa E and SLivingstone London UK 2nd edition 1962

[11] B E van Wyk A de Castro P M Tilney P J D Winter andA R Magee ldquoA new species of Alepidea (Apiaceae subfamSaniculoideae)rdquo South African Journal of Botany vol 74 no 4pp 740ndash745 2008

[12] J T Mukinda and P F K Eagles ldquoThe South African Pharma-copoeia Monograph Projectrdquo Developed by South African Tra-ditional Medicines Research Group (SATMERG) and Schoolof Pharmacy University of the Western Cape (Unpublished)2010

[13] A Mapaura and J R Timberlake ldquoSouthern African plantred data listsrdquo Southern African Botanical Diversity Network(SABONET) Report 14 SABONET Pretoria South Africa

[14] A Maroyi ldquoEthnobotanical study of two threatened medicinalplants in Zimbabwerdquo International Journal of Biodiversity Sci-ence and Management vol 4 no 3 pp 148ndash153 2008

[15] S Talukdar ldquoLesothordquo in Southern African Plant Red Data ListsJ Golding Ed Southern African Botanical Diversity Network(SABONET) Report Number 14 pp 21ndash30 SABONET Preto-ria South Africa 2002

[16] R Scott-Shaw ldquoRare and threatened plants of KwaZulu-Nataland neighbouring regionsrdquo in A Plant Red Data Book p182 KwaZulu-Natal Nature Conservation Service Pietermar-itzburg South Africa 1999

Evidence-Based Complementary and Alternative Medicine 11

[17] The Plant List 2012 httpwwwtheplantlistorg[18] S Nonjinge and B B Tarr Natal National Botanical Garden

2013 httpwwwplantzafricacomplantabalipedeamathtm[19] M Gelfand S Mavi R B Drummond and B Ndemera The

Traditional Medical Practitioner in Zimbabwe Mambo PressGweru Zimbabwe 1985

[20] B E VanWyk and N Gericke rsquoPeoplersquos PlantsmdashA Guide toUseful Plants of South Africa Briza Publication Pretoria SouthAfrica 2000

[21] A Hutchings A H Scott G Lewis and A CunninghamZulu Medicinal Plants An Inventory University of Natal PressScottsville South Africa 1996

[22] B E van Wyk B van Oudtshoorn and N Gericke MedicinalPlants of South Africa Briza Publications Pretoria SouthAfrica 1997

[23] J A Guillarmod Flora of Lesotho J Cramer Lehre Germany1971

[24] L I Somova F O Shode K Moodley and Y GovenderldquoCardiovascular and diuretic activity of kaurene derivativesof Xylopia aethiopica and Alepidea amatymbicardquo Journal ofEthnopharmacology vol 77 no 2-3 pp 165ndash174 2001

[25] J Pujol NaturAfrica The Herbalists Handbook Jean PujolNatural Healers Foundation Durban South Africa 1990

[26] A Hutchings and J van Staden ldquoPlants used for stress-relatedailments in traditional Zulu Xhosa and Sotho medicine Part 1plants used for headachesrdquo Journal of Ethnopharmacology vol43 no 2 pp 89ndash124 1994

[27] A Hutchings ldquorsquoObservations on plant usage in Xhosa and Zulumedicinerdquo Bothalia vol 19 pp 225ndash235 1989

[28] J F Sobiecki ldquoA preliminary inventory of plants used forpsychoactive purposes in southern African healing traditionsrdquoTransactions of the Royal Society of SouthAfrica vol 57 pp 1ndash242002

[29] S O Bandeira F Gaspar and F P Pagula ldquoAfrican ethnobotanyand healthcare emphasis on Mozambiquerdquo PharmaceuticalBiology vol 39 pp 70ndash73 2001

[30] A Rustaiyan and A S Sadjadi ldquoKaurene derivatives fromAlepidea amatynsiardquo Phytochemistry vol 26 no 7 pp 2106ndash2107 1987

[31] C W Holzapfel B E van Wyk A de Castro W Marais andM Herbst ldquoA chemotaxonomic survey of kaurene derivativesin the genus Alepidea (Apiaceae)rdquo Biochemical Systematics andEcology vol 23 no 7-8 pp 799ndash803 1995

[32] D K Olivier B van Wyk and F R van Heerden ldquoThechemotaxonomic and medicinal significance of phenolic acidsin Arctopus and Alepidea (Apiaceae subfamily Saniculoideae)rdquoBiochemical Systematics and Ecology vol 36 no 9 pp 724ndash7292008

[33] G I Stafford A K Jager and J van Staden ldquoEffect ofstorage on the chemical composition and biological activityof several popular South African medicinal plantsrdquo Journal ofEthnopharmacology vol 97 no 1 pp 107ndash115 2005

[34] C Clarkson V JMaharaj N R Crouch et al ldquoIn vitro antiplas-modial activity of medicinal plants native to or naturalised inSouth Africardquo Journal of Ethnopharmacology vol 92 no 2-3pp 177ndash191 2004

[35] F T TreurnichtAn evaluation of the toxic and potential antiviraleffects of some plants used by South Africans for medicinalpurposes [MS thesis] University of Stellenbosch StellenboschSouth Africa 1997

[36] A Hutchings Zulu Medicinal Plants Natal University PressPietermaritzburg South Africa 1996

[37] C I Wright L van-Buren C I Kroner and M M GKoning ldquoHerbalmedicines as diuretics a reviewof the scientificevidencerdquo Journal of Ethnopharmacology vol 114 no 1 pp 1ndash312007

[38] F O Shode and B C Rogers ldquoThe chemistry of ApiaceaeIsolation and characterisation of diterpenoids and other ter-penoids from Alepidea amatymbicardquo in Proceedings of the 7thInternational Chemistry Conference in Africa Durban SouthAfrica 1998

[39] C W Fennell M E Light S G Sparg G I Stafford and JVan Staden ldquoAssessingAfricanmedicinal plants for efficacy andsafety agricultural and storage practicesrdquo Journal of Ethnophar-macology vol 95 no 2-3 pp 113ndash121 2004

[40] D Luseba E E Elgorashi D T Ntloedibe and J Van StadenldquoAntibacterial anti-inflammatory and mutagenic effects ofsome medicinal plants used in South Africa for the treatmentof wounds and retained placenta in livestockrdquo South AfricanJournal of Botany vol 73 no 3 pp 378ndash383 2007

Submit your manuscripts athttpwwwhindawicom

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Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

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Behavioural Neurology

EndocrinologyInternational Journal of

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Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Disease Markers

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BioMed Research International

OncologyJournal of

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Oxidative Medicine and Cellular Longevity

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Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

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ObesityJournal of

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Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Computational and Mathematical Methods in Medicine

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Research and TreatmentAIDS

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Gastroenterology Research and Practice

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Parkinsonrsquos Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom

Page 9: Review Article Alepidea amatymbica Eckl. & Zeyh.: A Review ...downloads.hindawi.com/journals/ecam/2014/284517.pdf · A Review of Its Traditional Uses, Phytochemistry, Pharmacology,

Evidence-Based Complementary and Alternative Medicine 9

stem rhizome and root exhibited activity against Candidaalbicans extracts and more than 50 mycotic inhibitionagainst fungal cultures [6] This study does not provide adose dependent evidence of the extract and negative controlwas not used in validating the traditional use of the plantas antifungal Also all the extracts except acetone extractshowed mycotic inhibition activity against Aspergillus flavusandAspergillus niger [8]These results validate the traditionaluses of the plant as an antifungal but no dose dependentevidencewas given in this study and positive control drugwasnot used in comparison with the extract used Therefore theantifungal activity of the extract cannot be compared with anantifungal drug

53 Antiviral Louvel et al [2] investigated the screeningactivity of the aerial part and root aqueous extract of Aamatymbica against a cell-based infection assay targeting thereplication of prototypic CXCR4-tropic (NL4-3) or CCR5-tropic (NL-AD87) HIV-1 strains designed to detect inhibitorsblocking any step of the viral life cycle The active ingredientidentified in the extract does not support a direct applicationof this plant extract for treating HIV infection The anti-HIV activity of the pure compound was found to be quitemoderate Lack of negative control and a dose dependentactivity of the extract make the antiviral activity of the extractinconclusive

54 Antihelminthes Research was undertaken using nema-tode growth agar with Caenorhabditis elegans var Bristol(N2)nematodes on the ethanol extract of the fresh and storedleaves and root ofA amatymbicaOnly fresh and storedwaterextracts showed a significant Anthelminthic [33] The resultof the study did not evaluate a dose dependent inhibitionof the extract against the worms even though the controlswere compared with the extract Further investigation isthus required to validate the use of the plant in traditionalmedicine as antihelmintic

55 Anti-Inflammatory The DCM PE water and EtOHrhizome extracts were evaluated using the enzyme basedcyclooxygenase assays COX-1 and COX-2 [6] The PE andDCM extracts had high COX-1 and COX-2 activities withpercentage inhibitions above 70 Ethanol extracts showedhigher inhibition (lt40) in COX-1 than COX-2 The waterextract on the other hand has a moderate inhibition activ-ity (40ndash60) in COX-1 and lowered in COX-2 (lt20)Despite reports on the undesirable effects of higher COX-1 inhibition as a result of its damage to the gastrointestinaltract [40] report of Mulaudzi et al [6] recorded a higherCOX-1 in both DCM and PE and a lower COX-1 inhibitionin ethanol and water The result favors the use of waterand ethanol as a solvent of extraction for this plant whenusing it against inflammation However conclusion cannotbe totally drawn on this report due to lack of negativecontrol and dosage Hence further investigation is required toprovide an evidence for its traditional use against inflamma-tion

56 Antihypertensive Hexane extractive (AA1) dichloro-methane extractive and methanol extractive of the fresh rhi-zome were investigated using purified compounds on bloodpressure and heart rate of anesthetizedWistar rats Moderatebut significant decrease in systolic blood pressure (SBP) andheart rate (HT) effects after intraperitoneal application onconscious rats was reported [24]

57 Antiplasmodium Dichloromethane (DCM) DCMmethanol (MeOH) (1 1) MeOH and purified water extractfrom the whole plant were investigated on plasmodialactivity and were found to contain plant based antimalarialagents showing promising antiplasmodial activity with IC

50

values of le10 gmL [34] This is the only study showing thedose dependent antiplasmodic activity of the plant extractin relation to the positive control Validation of the use ofthe plant in vivo is necessary to conclude the antiplasmodialactivity of A amatymbica

58 Diuretic The purified compounds of the fresh rhizomeextracted in hexaneethyl acetate of A amatymbica wereinvestigated using anesthetized Wistar rats The diuretic andnatriuretic effects of the extractives were found to be similarto the effects of chlorothiazide drug [24] The result suggeststhe inhibitory effect of the extractive of A amatymbica inreabsorption of K+ and Na+ ions suggesting the diureticand natriuretic effects of the extractives Lack of testedextractive in a dose dependent manner however negates thevalidation of the plants and the extractives for use as diuretictraditionally Further investigation is required to provideevidence for its use as a diuretic

6 Toxicological Reports

Four toxicity screens were identified in the literature Eachof the four screens tested uses crude aqueous and organicsolvents hexane extracts and extractives from the crudehexane extract and none of the reports recorded toxicity atall doses testedThe reported cytotoxicity of the fresh aqueousrhizome was investigated using HeLa Vero and Jurkat E61AA-2 or CEM-SS cells The extract was shown not to betoxic at all concentrations used in the test [35] since thedosage and controls were shown in this study in comparisonwith the control The second screens use bacterial cultures(100 120583L) in an Amen test assay which were added to 100120583L ofDCM PE water and EtOH rhizome plant extracts in 500120583Lphosphate buffer and 2mLof agar containing biotin-histidine(05mM) The Ames test revealed that none of the plantextracts significantly increased the number ofHis+ revertantswith respect to the negative control [6] The third test screenutilised the Brine Shrimp Lethal Assay (BSLA) Acute toxicityof the isolates from Alepidea amatymbica was screen againstbrine shrimp Artemia salina intersection bioassay The brineshrimp test showed that the crude hexane extracts have lowtoxicity with LC

5002 ngmL while the AA6 (wedelia seco-

kaurenolide) a derivative of A amatymbica has a low toxicityof 05 ngmL [24]The fourth screenmade use of Hippocratictest on rats with the use of hexane (AA1) extract and itrsquos

10 Evidence-Based Complementary and Alternative Medicine

extractives in dichloromethane and methanol (AA1) aftersubjection to repeated flash chromatography with gradientelution (100ndash70 hexaneEtOAc) to give AA3 a crystallinemixture of ent-kaur-en-19-oic acid ent-kaura-9 (11) 16-dien-19-oic acid and trachyloban-19-oic acid AA4 16-methoxy-ent-kaur-11-en-19-oic acid AA5 11-acetoxy-ent-kaur-16-en-19-oic acid and AA6 wedelia seco-kaurenolide All extractscrude and purified showed low toxicity ranging from 05 to5 ngmL (LC

50) apart from AA4 and AA5 that produced

slight diarrhea on days 3 4 and 5 and other extractivesshowed no toxicity at a dose of 20 [24] Apart from thestudies of Treurnicht [35] and Mulaudzi et al [6] mentionedabove the other studies do not provide sufficient evidencewith respect to the safety of A amatymbica considering theabsence of dosage used and control in their assays

7 Clinical Trials

To date there appears to be no published research indicatingthat extracts ofAlepidea amatymbica have undergone humanclinical trials

8 Conclusion

The review showed that A amatymbica has a widespread usein South Africa and other SADEC countriesThe recognitionof its ethnomedicinal usage for conditions of inflammationlike rheumatism and sore throat to usage for wounds coughasthma influenza diarrhea stomach cramps abdominal dis-orders malaria and diuretic is worth mentioningThe abilityof the extract to also restrain the growth of bacteria and fungiindicated its broad spectrum antimicrobial prospective Thepharmacological reports on A amatymbica revealed thera-peutic potential in the treatment of inflammation malariaand infectious diseases like influenza cough and diarrheaThe frequently occurring chemical constituents of Alepideaamatymbica belong to the kaurene-type diterpenoids andtheir derivatives Literature search onA amatymbica revealedthe use of cell line brine shrimps and rats for the determi-nation of the toxicity in the plant More investigations arenecessary to explore themedicinal potential of the plant in themanagement of rheumatism asthma hypertension diureticand inflammation Clinical trials and product development tofully exploit the medicinal value are also required to validateits folklore use in traditional medicine There is thereforethe need to develop the existing traditional use of this plantto amplify nutraceuticals product and commence clinicalresearch to exploit the plantrsquos novel phytochemicals

Conflict of Interests

The authors declare no conflict of interests

Acknowledgments

The authors are thankful to the Govan Mbeki Research andDevelopment Centre and the National Research Fund of theUniversity of Fort Hare South Africa

References

[1] B l Burtt ldquoUmbelliferae of southern Africa an introductionand annotated checklistrdquo Edinburgh Journal of Botany vol 48pp 133ndash282 1991

[2] S Louvel N Moodley I Seibert et al ldquoIdentification ofcompounds from the plant species Alepidea amatymbica activeagainst HIVrdquo South African Journal of Botany vol 86 pp 9ndash142013

[3] G Germishuizen N L Meyer Y Steenkamp and M KeithPlants of Southern Africa An Annotated Checklist vol 41 ofSABONET Report National Botanical Institute Pretoria SouthAfrica 2006

[4] R R Klopper P Lemmer and J Nel ldquoPteridophyta Pteridaceaecheilanthes deltoidea a new locality in Gauteng South AfricardquoBothalia vol 36 no 2 pp 173ndash174 2006

[5] Z Maksimovic S Dobric N Kovacevic and Z MilovanovicldquoDiuretic activity of Maydis stigma extract in ratsrdquo Pharmazievol 59 no 12 pp 967ndash971 2004

[6] R B Mulaudzi A R Ndhlala J F Finnie and J Van StadenldquoAntimicrobial anti-inflammatory and genotoxicity activityof Alepidea amatymbica and Alepidea natalensis (Apiaceae)rdquoSouth African Journal of Botany vol 75 no 3 pp 584ndash587 2009

[7] A de Castro and B-E van Wyk ldquoDiagnostic characters andgeographic distribution of Alepidea species used in traditionalmedicinerdquo South African Journal of Botany vol 60 no 6 pp345ndash350 1994

[8] A J Afolayan and F B Lewu ldquoAntimicrobial activity ofAlepideaamatymbicardquo Pharmaceutical Biology vol 47 no 5 pp 436ndash439 2009

[9] C Njume A A Jide and R N Ndip ldquoAqueous and organicsolvent-extracts of selected South African medicinal plantspossess antimicrobial activity against drug-resistant strainsof Helicobacter pylori inhibitory and bactericidal potentialrdquoInternational Journal of Molecular Sciences vol 12 no 9 pp5652ndash5665 2011

[10] J M Watt and M G Breyer-Brandwijik The Medicinal andPoisonous Plants of Southern and Eastern Africa E and SLivingstone London UK 2nd edition 1962

[11] B E van Wyk A de Castro P M Tilney P J D Winter andA R Magee ldquoA new species of Alepidea (Apiaceae subfamSaniculoideae)rdquo South African Journal of Botany vol 74 no 4pp 740ndash745 2008

[12] J T Mukinda and P F K Eagles ldquoThe South African Pharma-copoeia Monograph Projectrdquo Developed by South African Tra-ditional Medicines Research Group (SATMERG) and Schoolof Pharmacy University of the Western Cape (Unpublished)2010

[13] A Mapaura and J R Timberlake ldquoSouthern African plantred data listsrdquo Southern African Botanical Diversity Network(SABONET) Report 14 SABONET Pretoria South Africa

[14] A Maroyi ldquoEthnobotanical study of two threatened medicinalplants in Zimbabwerdquo International Journal of Biodiversity Sci-ence and Management vol 4 no 3 pp 148ndash153 2008

[15] S Talukdar ldquoLesothordquo in Southern African Plant Red Data ListsJ Golding Ed Southern African Botanical Diversity Network(SABONET) Report Number 14 pp 21ndash30 SABONET Preto-ria South Africa 2002

[16] R Scott-Shaw ldquoRare and threatened plants of KwaZulu-Nataland neighbouring regionsrdquo in A Plant Red Data Book p182 KwaZulu-Natal Nature Conservation Service Pietermar-itzburg South Africa 1999

Evidence-Based Complementary and Alternative Medicine 11

[17] The Plant List 2012 httpwwwtheplantlistorg[18] S Nonjinge and B B Tarr Natal National Botanical Garden

2013 httpwwwplantzafricacomplantabalipedeamathtm[19] M Gelfand S Mavi R B Drummond and B Ndemera The

Traditional Medical Practitioner in Zimbabwe Mambo PressGweru Zimbabwe 1985

[20] B E VanWyk and N Gericke rsquoPeoplersquos PlantsmdashA Guide toUseful Plants of South Africa Briza Publication Pretoria SouthAfrica 2000

[21] A Hutchings A H Scott G Lewis and A CunninghamZulu Medicinal Plants An Inventory University of Natal PressScottsville South Africa 1996

[22] B E van Wyk B van Oudtshoorn and N Gericke MedicinalPlants of South Africa Briza Publications Pretoria SouthAfrica 1997

[23] J A Guillarmod Flora of Lesotho J Cramer Lehre Germany1971

[24] L I Somova F O Shode K Moodley and Y GovenderldquoCardiovascular and diuretic activity of kaurene derivativesof Xylopia aethiopica and Alepidea amatymbicardquo Journal ofEthnopharmacology vol 77 no 2-3 pp 165ndash174 2001

[25] J Pujol NaturAfrica The Herbalists Handbook Jean PujolNatural Healers Foundation Durban South Africa 1990

[26] A Hutchings and J van Staden ldquoPlants used for stress-relatedailments in traditional Zulu Xhosa and Sotho medicine Part 1plants used for headachesrdquo Journal of Ethnopharmacology vol43 no 2 pp 89ndash124 1994

[27] A Hutchings ldquorsquoObservations on plant usage in Xhosa and Zulumedicinerdquo Bothalia vol 19 pp 225ndash235 1989

[28] J F Sobiecki ldquoA preliminary inventory of plants used forpsychoactive purposes in southern African healing traditionsrdquoTransactions of the Royal Society of SouthAfrica vol 57 pp 1ndash242002

[29] S O Bandeira F Gaspar and F P Pagula ldquoAfrican ethnobotanyand healthcare emphasis on Mozambiquerdquo PharmaceuticalBiology vol 39 pp 70ndash73 2001

[30] A Rustaiyan and A S Sadjadi ldquoKaurene derivatives fromAlepidea amatynsiardquo Phytochemistry vol 26 no 7 pp 2106ndash2107 1987

[31] C W Holzapfel B E van Wyk A de Castro W Marais andM Herbst ldquoA chemotaxonomic survey of kaurene derivativesin the genus Alepidea (Apiaceae)rdquo Biochemical Systematics andEcology vol 23 no 7-8 pp 799ndash803 1995

[32] D K Olivier B van Wyk and F R van Heerden ldquoThechemotaxonomic and medicinal significance of phenolic acidsin Arctopus and Alepidea (Apiaceae subfamily Saniculoideae)rdquoBiochemical Systematics and Ecology vol 36 no 9 pp 724ndash7292008

[33] G I Stafford A K Jager and J van Staden ldquoEffect ofstorage on the chemical composition and biological activityof several popular South African medicinal plantsrdquo Journal ofEthnopharmacology vol 97 no 1 pp 107ndash115 2005

[34] C Clarkson V JMaharaj N R Crouch et al ldquoIn vitro antiplas-modial activity of medicinal plants native to or naturalised inSouth Africardquo Journal of Ethnopharmacology vol 92 no 2-3pp 177ndash191 2004

[35] F T TreurnichtAn evaluation of the toxic and potential antiviraleffects of some plants used by South Africans for medicinalpurposes [MS thesis] University of Stellenbosch StellenboschSouth Africa 1997

[36] A Hutchings Zulu Medicinal Plants Natal University PressPietermaritzburg South Africa 1996

[37] C I Wright L van-Buren C I Kroner and M M GKoning ldquoHerbalmedicines as diuretics a reviewof the scientificevidencerdquo Journal of Ethnopharmacology vol 114 no 1 pp 1ndash312007

[38] F O Shode and B C Rogers ldquoThe chemistry of ApiaceaeIsolation and characterisation of diterpenoids and other ter-penoids from Alepidea amatymbicardquo in Proceedings of the 7thInternational Chemistry Conference in Africa Durban SouthAfrica 1998

[39] C W Fennell M E Light S G Sparg G I Stafford and JVan Staden ldquoAssessingAfricanmedicinal plants for efficacy andsafety agricultural and storage practicesrdquo Journal of Ethnophar-macology vol 95 no 2-3 pp 113ndash121 2004

[40] D Luseba E E Elgorashi D T Ntloedibe and J Van StadenldquoAntibacterial anti-inflammatory and mutagenic effects ofsome medicinal plants used in South Africa for the treatmentof wounds and retained placenta in livestockrdquo South AfricanJournal of Botany vol 73 no 3 pp 378ndash383 2007

Submit your manuscripts athttpwwwhindawicom

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MEDIATORSINFLAMMATION

of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Behavioural Neurology

EndocrinologyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Disease Markers

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

OncologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Oxidative Medicine and Cellular Longevity

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

PPAR Research

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

ObesityJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Computational and Mathematical Methods in Medicine

OphthalmologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Diabetes ResearchJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Research and TreatmentAIDS

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Gastroenterology Research and Practice

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Parkinsonrsquos Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom

Page 10: Review Article Alepidea amatymbica Eckl. & Zeyh.: A Review ...downloads.hindawi.com/journals/ecam/2014/284517.pdf · A Review of Its Traditional Uses, Phytochemistry, Pharmacology,

10 Evidence-Based Complementary and Alternative Medicine

extractives in dichloromethane and methanol (AA1) aftersubjection to repeated flash chromatography with gradientelution (100ndash70 hexaneEtOAc) to give AA3 a crystallinemixture of ent-kaur-en-19-oic acid ent-kaura-9 (11) 16-dien-19-oic acid and trachyloban-19-oic acid AA4 16-methoxy-ent-kaur-11-en-19-oic acid AA5 11-acetoxy-ent-kaur-16-en-19-oic acid and AA6 wedelia seco-kaurenolide All extractscrude and purified showed low toxicity ranging from 05 to5 ngmL (LC

50) apart from AA4 and AA5 that produced

slight diarrhea on days 3 4 and 5 and other extractivesshowed no toxicity at a dose of 20 [24] Apart from thestudies of Treurnicht [35] and Mulaudzi et al [6] mentionedabove the other studies do not provide sufficient evidencewith respect to the safety of A amatymbica considering theabsence of dosage used and control in their assays

7 Clinical Trials

To date there appears to be no published research indicatingthat extracts ofAlepidea amatymbica have undergone humanclinical trials

8 Conclusion

The review showed that A amatymbica has a widespread usein South Africa and other SADEC countriesThe recognitionof its ethnomedicinal usage for conditions of inflammationlike rheumatism and sore throat to usage for wounds coughasthma influenza diarrhea stomach cramps abdominal dis-orders malaria and diuretic is worth mentioningThe abilityof the extract to also restrain the growth of bacteria and fungiindicated its broad spectrum antimicrobial prospective Thepharmacological reports on A amatymbica revealed thera-peutic potential in the treatment of inflammation malariaand infectious diseases like influenza cough and diarrheaThe frequently occurring chemical constituents of Alepideaamatymbica belong to the kaurene-type diterpenoids andtheir derivatives Literature search onA amatymbica revealedthe use of cell line brine shrimps and rats for the determi-nation of the toxicity in the plant More investigations arenecessary to explore themedicinal potential of the plant in themanagement of rheumatism asthma hypertension diureticand inflammation Clinical trials and product development tofully exploit the medicinal value are also required to validateits folklore use in traditional medicine There is thereforethe need to develop the existing traditional use of this plantto amplify nutraceuticals product and commence clinicalresearch to exploit the plantrsquos novel phytochemicals

Conflict of Interests

The authors declare no conflict of interests

Acknowledgments

The authors are thankful to the Govan Mbeki Research andDevelopment Centre and the National Research Fund of theUniversity of Fort Hare South Africa

References

[1] B l Burtt ldquoUmbelliferae of southern Africa an introductionand annotated checklistrdquo Edinburgh Journal of Botany vol 48pp 133ndash282 1991

[2] S Louvel N Moodley I Seibert et al ldquoIdentification ofcompounds from the plant species Alepidea amatymbica activeagainst HIVrdquo South African Journal of Botany vol 86 pp 9ndash142013

[3] G Germishuizen N L Meyer Y Steenkamp and M KeithPlants of Southern Africa An Annotated Checklist vol 41 ofSABONET Report National Botanical Institute Pretoria SouthAfrica 2006

[4] R R Klopper P Lemmer and J Nel ldquoPteridophyta Pteridaceaecheilanthes deltoidea a new locality in Gauteng South AfricardquoBothalia vol 36 no 2 pp 173ndash174 2006

[5] Z Maksimovic S Dobric N Kovacevic and Z MilovanovicldquoDiuretic activity of Maydis stigma extract in ratsrdquo Pharmazievol 59 no 12 pp 967ndash971 2004

[6] R B Mulaudzi A R Ndhlala J F Finnie and J Van StadenldquoAntimicrobial anti-inflammatory and genotoxicity activityof Alepidea amatymbica and Alepidea natalensis (Apiaceae)rdquoSouth African Journal of Botany vol 75 no 3 pp 584ndash587 2009

[7] A de Castro and B-E van Wyk ldquoDiagnostic characters andgeographic distribution of Alepidea species used in traditionalmedicinerdquo South African Journal of Botany vol 60 no 6 pp345ndash350 1994

[8] A J Afolayan and F B Lewu ldquoAntimicrobial activity ofAlepideaamatymbicardquo Pharmaceutical Biology vol 47 no 5 pp 436ndash439 2009

[9] C Njume A A Jide and R N Ndip ldquoAqueous and organicsolvent-extracts of selected South African medicinal plantspossess antimicrobial activity against drug-resistant strainsof Helicobacter pylori inhibitory and bactericidal potentialrdquoInternational Journal of Molecular Sciences vol 12 no 9 pp5652ndash5665 2011

[10] J M Watt and M G Breyer-Brandwijik The Medicinal andPoisonous Plants of Southern and Eastern Africa E and SLivingstone London UK 2nd edition 1962

[11] B E van Wyk A de Castro P M Tilney P J D Winter andA R Magee ldquoA new species of Alepidea (Apiaceae subfamSaniculoideae)rdquo South African Journal of Botany vol 74 no 4pp 740ndash745 2008

[12] J T Mukinda and P F K Eagles ldquoThe South African Pharma-copoeia Monograph Projectrdquo Developed by South African Tra-ditional Medicines Research Group (SATMERG) and Schoolof Pharmacy University of the Western Cape (Unpublished)2010

[13] A Mapaura and J R Timberlake ldquoSouthern African plantred data listsrdquo Southern African Botanical Diversity Network(SABONET) Report 14 SABONET Pretoria South Africa

[14] A Maroyi ldquoEthnobotanical study of two threatened medicinalplants in Zimbabwerdquo International Journal of Biodiversity Sci-ence and Management vol 4 no 3 pp 148ndash153 2008

[15] S Talukdar ldquoLesothordquo in Southern African Plant Red Data ListsJ Golding Ed Southern African Botanical Diversity Network(SABONET) Report Number 14 pp 21ndash30 SABONET Preto-ria South Africa 2002

[16] R Scott-Shaw ldquoRare and threatened plants of KwaZulu-Nataland neighbouring regionsrdquo in A Plant Red Data Book p182 KwaZulu-Natal Nature Conservation Service Pietermar-itzburg South Africa 1999

Evidence-Based Complementary and Alternative Medicine 11

[17] The Plant List 2012 httpwwwtheplantlistorg[18] S Nonjinge and B B Tarr Natal National Botanical Garden

2013 httpwwwplantzafricacomplantabalipedeamathtm[19] M Gelfand S Mavi R B Drummond and B Ndemera The

Traditional Medical Practitioner in Zimbabwe Mambo PressGweru Zimbabwe 1985

[20] B E VanWyk and N Gericke rsquoPeoplersquos PlantsmdashA Guide toUseful Plants of South Africa Briza Publication Pretoria SouthAfrica 2000

[21] A Hutchings A H Scott G Lewis and A CunninghamZulu Medicinal Plants An Inventory University of Natal PressScottsville South Africa 1996

[22] B E van Wyk B van Oudtshoorn and N Gericke MedicinalPlants of South Africa Briza Publications Pretoria SouthAfrica 1997

[23] J A Guillarmod Flora of Lesotho J Cramer Lehre Germany1971

[24] L I Somova F O Shode K Moodley and Y GovenderldquoCardiovascular and diuretic activity of kaurene derivativesof Xylopia aethiopica and Alepidea amatymbicardquo Journal ofEthnopharmacology vol 77 no 2-3 pp 165ndash174 2001

[25] J Pujol NaturAfrica The Herbalists Handbook Jean PujolNatural Healers Foundation Durban South Africa 1990

[26] A Hutchings and J van Staden ldquoPlants used for stress-relatedailments in traditional Zulu Xhosa and Sotho medicine Part 1plants used for headachesrdquo Journal of Ethnopharmacology vol43 no 2 pp 89ndash124 1994

[27] A Hutchings ldquorsquoObservations on plant usage in Xhosa and Zulumedicinerdquo Bothalia vol 19 pp 225ndash235 1989

[28] J F Sobiecki ldquoA preliminary inventory of plants used forpsychoactive purposes in southern African healing traditionsrdquoTransactions of the Royal Society of SouthAfrica vol 57 pp 1ndash242002

[29] S O Bandeira F Gaspar and F P Pagula ldquoAfrican ethnobotanyand healthcare emphasis on Mozambiquerdquo PharmaceuticalBiology vol 39 pp 70ndash73 2001

[30] A Rustaiyan and A S Sadjadi ldquoKaurene derivatives fromAlepidea amatynsiardquo Phytochemistry vol 26 no 7 pp 2106ndash2107 1987

[31] C W Holzapfel B E van Wyk A de Castro W Marais andM Herbst ldquoA chemotaxonomic survey of kaurene derivativesin the genus Alepidea (Apiaceae)rdquo Biochemical Systematics andEcology vol 23 no 7-8 pp 799ndash803 1995

[32] D K Olivier B van Wyk and F R van Heerden ldquoThechemotaxonomic and medicinal significance of phenolic acidsin Arctopus and Alepidea (Apiaceae subfamily Saniculoideae)rdquoBiochemical Systematics and Ecology vol 36 no 9 pp 724ndash7292008

[33] G I Stafford A K Jager and J van Staden ldquoEffect ofstorage on the chemical composition and biological activityof several popular South African medicinal plantsrdquo Journal ofEthnopharmacology vol 97 no 1 pp 107ndash115 2005

[34] C Clarkson V JMaharaj N R Crouch et al ldquoIn vitro antiplas-modial activity of medicinal plants native to or naturalised inSouth Africardquo Journal of Ethnopharmacology vol 92 no 2-3pp 177ndash191 2004

[35] F T TreurnichtAn evaluation of the toxic and potential antiviraleffects of some plants used by South Africans for medicinalpurposes [MS thesis] University of Stellenbosch StellenboschSouth Africa 1997

[36] A Hutchings Zulu Medicinal Plants Natal University PressPietermaritzburg South Africa 1996

[37] C I Wright L van-Buren C I Kroner and M M GKoning ldquoHerbalmedicines as diuretics a reviewof the scientificevidencerdquo Journal of Ethnopharmacology vol 114 no 1 pp 1ndash312007

[38] F O Shode and B C Rogers ldquoThe chemistry of ApiaceaeIsolation and characterisation of diterpenoids and other ter-penoids from Alepidea amatymbicardquo in Proceedings of the 7thInternational Chemistry Conference in Africa Durban SouthAfrica 1998

[39] C W Fennell M E Light S G Sparg G I Stafford and JVan Staden ldquoAssessingAfricanmedicinal plants for efficacy andsafety agricultural and storage practicesrdquo Journal of Ethnophar-macology vol 95 no 2-3 pp 113ndash121 2004

[40] D Luseba E E Elgorashi D T Ntloedibe and J Van StadenldquoAntibacterial anti-inflammatory and mutagenic effects ofsome medicinal plants used in South Africa for the treatmentof wounds and retained placenta in livestockrdquo South AfricanJournal of Botany vol 73 no 3 pp 378ndash383 2007

Submit your manuscripts athttpwwwhindawicom

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MEDIATORSINFLAMMATION

of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Behavioural Neurology

EndocrinologyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Disease Markers

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

OncologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Oxidative Medicine and Cellular Longevity

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

PPAR Research

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

ObesityJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Computational and Mathematical Methods in Medicine

OphthalmologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Diabetes ResearchJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Research and TreatmentAIDS

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Gastroenterology Research and Practice

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Parkinsonrsquos Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom

Page 11: Review Article Alepidea amatymbica Eckl. & Zeyh.: A Review ...downloads.hindawi.com/journals/ecam/2014/284517.pdf · A Review of Its Traditional Uses, Phytochemistry, Pharmacology,

Evidence-Based Complementary and Alternative Medicine 11

[17] The Plant List 2012 httpwwwtheplantlistorg[18] S Nonjinge and B B Tarr Natal National Botanical Garden

2013 httpwwwplantzafricacomplantabalipedeamathtm[19] M Gelfand S Mavi R B Drummond and B Ndemera The

Traditional Medical Practitioner in Zimbabwe Mambo PressGweru Zimbabwe 1985

[20] B E VanWyk and N Gericke rsquoPeoplersquos PlantsmdashA Guide toUseful Plants of South Africa Briza Publication Pretoria SouthAfrica 2000

[21] A Hutchings A H Scott G Lewis and A CunninghamZulu Medicinal Plants An Inventory University of Natal PressScottsville South Africa 1996

[22] B E van Wyk B van Oudtshoorn and N Gericke MedicinalPlants of South Africa Briza Publications Pretoria SouthAfrica 1997

[23] J A Guillarmod Flora of Lesotho J Cramer Lehre Germany1971

[24] L I Somova F O Shode K Moodley and Y GovenderldquoCardiovascular and diuretic activity of kaurene derivativesof Xylopia aethiopica and Alepidea amatymbicardquo Journal ofEthnopharmacology vol 77 no 2-3 pp 165ndash174 2001

[25] J Pujol NaturAfrica The Herbalists Handbook Jean PujolNatural Healers Foundation Durban South Africa 1990

[26] A Hutchings and J van Staden ldquoPlants used for stress-relatedailments in traditional Zulu Xhosa and Sotho medicine Part 1plants used for headachesrdquo Journal of Ethnopharmacology vol43 no 2 pp 89ndash124 1994

[27] A Hutchings ldquorsquoObservations on plant usage in Xhosa and Zulumedicinerdquo Bothalia vol 19 pp 225ndash235 1989

[28] J F Sobiecki ldquoA preliminary inventory of plants used forpsychoactive purposes in southern African healing traditionsrdquoTransactions of the Royal Society of SouthAfrica vol 57 pp 1ndash242002

[29] S O Bandeira F Gaspar and F P Pagula ldquoAfrican ethnobotanyand healthcare emphasis on Mozambiquerdquo PharmaceuticalBiology vol 39 pp 70ndash73 2001

[30] A Rustaiyan and A S Sadjadi ldquoKaurene derivatives fromAlepidea amatynsiardquo Phytochemistry vol 26 no 7 pp 2106ndash2107 1987

[31] C W Holzapfel B E van Wyk A de Castro W Marais andM Herbst ldquoA chemotaxonomic survey of kaurene derivativesin the genus Alepidea (Apiaceae)rdquo Biochemical Systematics andEcology vol 23 no 7-8 pp 799ndash803 1995

[32] D K Olivier B van Wyk and F R van Heerden ldquoThechemotaxonomic and medicinal significance of phenolic acidsin Arctopus and Alepidea (Apiaceae subfamily Saniculoideae)rdquoBiochemical Systematics and Ecology vol 36 no 9 pp 724ndash7292008

[33] G I Stafford A K Jager and J van Staden ldquoEffect ofstorage on the chemical composition and biological activityof several popular South African medicinal plantsrdquo Journal ofEthnopharmacology vol 97 no 1 pp 107ndash115 2005

[34] C Clarkson V JMaharaj N R Crouch et al ldquoIn vitro antiplas-modial activity of medicinal plants native to or naturalised inSouth Africardquo Journal of Ethnopharmacology vol 92 no 2-3pp 177ndash191 2004

[35] F T TreurnichtAn evaluation of the toxic and potential antiviraleffects of some plants used by South Africans for medicinalpurposes [MS thesis] University of Stellenbosch StellenboschSouth Africa 1997

[36] A Hutchings Zulu Medicinal Plants Natal University PressPietermaritzburg South Africa 1996

[37] C I Wright L van-Buren C I Kroner and M M GKoning ldquoHerbalmedicines as diuretics a reviewof the scientificevidencerdquo Journal of Ethnopharmacology vol 114 no 1 pp 1ndash312007

[38] F O Shode and B C Rogers ldquoThe chemistry of ApiaceaeIsolation and characterisation of diterpenoids and other ter-penoids from Alepidea amatymbicardquo in Proceedings of the 7thInternational Chemistry Conference in Africa Durban SouthAfrica 1998

[39] C W Fennell M E Light S G Sparg G I Stafford and JVan Staden ldquoAssessingAfricanmedicinal plants for efficacy andsafety agricultural and storage practicesrdquo Journal of Ethnophar-macology vol 95 no 2-3 pp 113ndash121 2004

[40] D Luseba E E Elgorashi D T Ntloedibe and J Van StadenldquoAntibacterial anti-inflammatory and mutagenic effects ofsome medicinal plants used in South Africa for the treatmentof wounds and retained placenta in livestockrdquo South AfricanJournal of Botany vol 73 no 3 pp 378ndash383 2007

Submit your manuscripts athttpwwwhindawicom

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MEDIATORSINFLAMMATION

of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Behavioural Neurology

EndocrinologyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Disease Markers

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

OncologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Oxidative Medicine and Cellular Longevity

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

PPAR Research

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

ObesityJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Computational and Mathematical Methods in Medicine

OphthalmologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Diabetes ResearchJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Research and TreatmentAIDS

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Gastroenterology Research and Practice

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Parkinsonrsquos Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom

Page 12: Review Article Alepidea amatymbica Eckl. & Zeyh.: A Review ...downloads.hindawi.com/journals/ecam/2014/284517.pdf · A Review of Its Traditional Uses, Phytochemistry, Pharmacology,

Submit your manuscripts athttpwwwhindawicom

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MEDIATORSINFLAMMATION

of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Behavioural Neurology

EndocrinologyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Disease Markers

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

OncologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Oxidative Medicine and Cellular Longevity

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

PPAR Research

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

ObesityJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Computational and Mathematical Methods in Medicine

OphthalmologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Diabetes ResearchJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Research and TreatmentAIDS

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Gastroenterology Research and Practice

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Parkinsonrsquos Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom


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