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Prof. Dr. Amani S. Awaad
Professor of PharmacognosyPharmacognosy Department,
College of Pharmacy Salman Bin Abdulaziz
University,
Al-Kharj. KSA.
Email: [email protected]
Pharmacognosy -2
PHG 322
*What are phenylpropanoids
their structures and synthesis
*Classes of Simple phenolic
*Lignins, their structures and biological
activates
The phenylpropanoids are a
diverse family of organic
compounds that are synthesized by
plants from the amino acid
phenylalanine.
Their name is derived from the
six-carbon, aromatic phenyl group
and the three-carbon propene tail
of cinnamic acid, which is
synthesized from phenylalanine in
the first step of phenylpropanoid
biosynthesis.
phenylpropanoids
Phenylpropanoids and other phenolics
drevatives are part of the chemical
composition of sporopollenin.
Phenylpropanoids
form a vast group of substances which is difficult to define in
simple terms. The fundamental structure element that
characterizes them
- is the presence of at least one aromatic
- ring substituted by at least one hydroxyl group, free or
engaged in another function: ether, ester or glycoside.
Phenols and Phenolic Acids
it would include secondary metabolites which possess these
structural elements, but which evidently belong to quite different
phytochemical groups.
• For example many alkaloids (e.g. boldine, morphine) and
• a fair number of terpenes (e.g. thymol, carnosol) have, within
their structure, an aromatic ring and a phenolic hydroxyl group!
• This is why a biosynthetic criterion is necessary to better define
the boundaries of the group.
Phenolic
Phenylpropanoids
Only plants and microorganisms are capable
of biologically synthesizing the aromatic
nucleus.
Animal organisms are almost always
dependent on either their nutrition or a
symbiosis to elaborate indispensable
metabolites comprising this structural element
(e.g. amino acids, vitamins, pigments, toxins)
the term Phenolic acid applies to all organic
compounds with at least one carboxyl group
and one Phenolic hydroxyl group.
Because their chemical and analytical
properties are not very different, and
because their pharmacological interests is
relatively limited, we shall present benzoic
acid (C6-C1) and cinnamic (C6-C3)
derivatives in the same place
Phenols and Phenolic Acids
Simple Phenols
phenylpropanoids
Phenols and Phenolic Acids
Simple phenols (seldom occur naturally), Except for hydroquinone which is found in several families (including Ericaceae, and Rosaceae), most often as the glucoside of the diphenol (arbutin) or of its monomethyl ether.Alkylphenols and their derivatives arise from the metabolism of polyketide are characteristic of Lichens.
The simple phenols consist of a singly substituted phenolic ring
with either alcoholic, aldehydic or carboxylic acid groups
Involved in defense against insect herbivores and fungi
Simple Phenols
Lichens.
OH
OH
O
OH
H
O
Simple Phenols
urushiol
few alkenylphenols (urushiol) and Phenolic monoterpenes (thymol) are known
Phenylpropanoids
Phenols and Phenolic Acids
Simple Phenolic acid
Types of simple phenolic acids
Their are two types of simple phenolic:
2- Hydroxycinnamate or Cinnamic Acid
Derivatives (C6-C3)
COOH
Benzoic acid Hydroxybenzoates
COO
OH
OH
Cinnamic Acid
OH
OOH
O
O
hydroxycinnamate
1-Hydroxybenzoates or Benzoic Acid
Derivatives( C6-C1)
Phenolic acids are the main polyphenols made by plants. The name
“phenolic acids”, in general, describes phenols that possess one carboxylic
acid function
Phenylpropanoids
Phenols and Phenolic AcidsSimple Phenolic acid
C6-C1 phenolic acids that are hydroxylated
derivatives of benzoic acid are quite common in
the free state, as well as combined into esters of
glycosides
Gallic acid and its dimmer (hexahydroxydiphenic
acid) are constituents of hydrolysable tannins.
phenolic acids & aldehydes corresponding to
these acids:
vanillin (the most widespread), anisaldehyde (in
some essential oils), and salicaldehyde, among
others.
Types of simple phenolic acids
1-Hydroxybenzoates or Benzoic Acid Derivatives( C6-C1)
hexahydroxydiphenic acid
anisaldehydevanillin
Salicaldehyde
Phenylpropanoids
Phenols and Phenolic Acids
Simple Phenolic acidTypes of simple phenolic acids
1-Hydroxybenzoates or Benzoic Acid Derivatives( C6-C1)
O-Gluc.
HO
OH
HO
Arbutine
hydroquinone
+ glucose
hydrlysis
Arbutin is the glucoside of the
hydroquinone ( diphenol or
monomethyl ether of hydroquinon)
Arbutin, shows anti-bacterial
activities
i-Arbutin
ii-Salicin
Salicin is an alcoholic β-glucoside.
obtained from several species
of Salix (willow) . Its has anti-
inflammatory activity
Phenylpropanoids
Phenols and Phenolic AcidsSimple Phenolic acidTypes of simple phenolic acids
2- Hydroxycinnamate or Cinnamic Acid
Derivatives (C6-C3)
A) They occur rarely in the free state, except as extraction artifacts, and are very often found esterified:
i-Esters of aliphathic alcohols eg,; *mono- and dicaffeoyltartaric acids(of Orthosiphon stamineeus, feruloyltartaric acid ( Echinaceae),caffeoylmalic acid (Parietaria officinalis)
ii-Esters of quinic acid (chlorogenic acid, widely distributed) ,(rosmarinic acid and lithospermic acids in Lamiaceae & Boraginaceae only)
B) They can also Amides (spermidine, or putrescine
derivatives),
c) combinations with sugars: glucose esters (most commonly)
D)glucose ethers (especially in the Apiaceae and Brassicaceae).
Most C6-C3 phenolic acids (p-coumaric, caffeic, ferulic, sinapic acids) are very widely distributed; others (o-coumaric, o-ferulic acids) are uncommon.
Phenylpropanoids
Phenols and Phenolic Acids
Simple Phenolic acidTypes of simple phenolic acids
2- Hydroxycinnamate or Cinnamic Acid Derivatives (C6-C3)
i-Coniferin
Abies alba
CH=CHCH2OH
OCH3
O-C6H11O5
H2O
enzym.
CH=CHCH2OH
OCH3
OH
CHO
OCH3
OH
Oxidation
Chromic acid
+ gluc. VanillineConiferin
a grayish-white, water-soluble
powder, obtained from the
cambium of coniferous trees and
from asparagus: used chiefly in the
manufacture of vanillin.
ii-Ferulic acid
abundant phenolic phytochemical
found in plant cell wall
components. strong antioxidant.
Most often it is used in combination
with vitamins C and E.Ferula communis
Phenylpropanoids
Phenylpropanoids or C6-C3 Derivatives
Another group of phenylpropanoid derivativesconsists of phenylpropanoid esters of a glycosidecomprising an oligosaccharide (di- or trisaccharide)and a dihydroxyphenylethanol molecule.
The phenylpropanoic acid is, most of the time, caffeicacid, although compounds have been isolated (forexample from plantains) in which is p-coumaric orferulic acid instead.
Similarly, the dihydroxyphenylethanol can be engagedin an ether linkage, or, in rare cases, hydroxylated inthe 2-position: 2-(3',4'-dihydroxyphenyl)-1,2-dihydroxyethane.
These molecules appear to be chiefly present only ingamopetalous plants, especially in Lamiales, Oleales,and to a lesser extent, in the Asterales
Phenylpropanoids
Phenylpropanoids
Pharmacological Applications and Uses
• The physiological or ecological role of these molecules is little understood.
• Their therapeutic interest is very limited:
• urinary antiseptic properties of arbutin,
• and anti-inflammatory properties of salicylates.
• The properties that tradition attributes to drugs such as rosemary or artichoke, are said to be due, in part to esters of cinnamic derivatives; however, pharmacological data are limited, and clinical trials are either nonexistent or of questionable methodology.
• Glycosidic phenylpropanoid esters have interesting pharmacological potential.
• Some are enzyme inhibitors:
• C-amp phosphodiesterase inhibition (plantamajoside),
• aldose reductase inhibition (verbascoside),
• Verbascoside, forsythiaside, and their homologs inhibit 5-lipoxygenase in human granulocytes, as well as in rat peritoneal cells;
• as a result, the formation of hydroperoxides and leukotrienes is inhibited, and this may be the basis of the use, in traditional oriental medicine (China, Japan), of Forsythia fruits for the treatment of inflammatory or allergic diseases.
• Note that several compounds in this series have antibacterial and antifungal properties, particularly against phytopathogenic organisms
Phenolic compounds
C6• Simple phenols,
Benzoquinones
C6-1
• Alkilphenol, Phenolic alcohol Phenolic aldehydes,Phenolic acids
C6-2• Acetophenones,
• Phenylacetic acids
C6-3
• Hydroxycinnamicacids, Coumarins, Phenylpropenes, Isocoumarins, Chrom
C6-4 • Naphthoquinone
One benzoic
C6-
C1-C6
• Xanthonoids
C6-
C2-C6
• Stilbenoids, Anthraquinones
C6-
C3-C6
• Chalconoids,
• Flavonoids
(C6-
C3)2
• Lignans,
• Neolignans
Two benzoic
(C6-C3)n,
• Lignins
(C6)n• Catechol
melanins
(C6-C3-C6
• Flavolans (Condensed tannins),Polyphenolic proteins,Polyphenols
polyphenols
reducing,
dimerization
polymerisation
Lignans
Lignins Coumarins
oxidation
+ malonat
3 molecules
flavonoids
Stilbens
p-hydroxycinnamic (p-coumaric) acid
Phenolic
acid
Acetophenones
Phenilacetate acids
Combined forms
of hydroxycinnamic
acids
Biosynthesis some natural compounds
LignansPlant products of low molecular weight formed primarily from
oxidative coupling of two p-propylphenol moieties at their beta carbon
atoms; products with units coupled in other ways are neolignans
Phenyl proanoid unit
O
O
C
C Liganoid unit
*derived from the Latin word lignum, meaning wood
*Lignin fills the spaces in the cell wall between
cellulose, hemicellulose, and pectin components
*Lignin is a cross-linked racemic macromolecule
with molecular masses in excess of 10,000 u.
There are three types of monolignol
monomers, methoxylated to various degrees:
p-coumaryl alcohol, coniferyl alcohol, and
sinapyl alcohol
Phenylpropanoids
Lignin in beech has 100:70:7 of coniferyl: sinapyl: para-coumaryl
Stilbenoids
Phenylpropanoids
Stelbines & Phenanthrens
Stilbenoids are hydroxylated derivatives of stilbene.
They have a C6-C2-C6 structure.
They are secondary products of heartwood formation
in trees that can act as phytoalexins. In chemical
terms, they are hydroxylated derivatives of stilbene
Phenanthrene is a polycyclic aromatic
hydrocarbon composed of three fused
benzene rings
Phenanthrens
Juncusol
• Drug Name: Uvae ursi Folium
• Description: The sapthulate and thick, leathery glabrous leaves are glossy green on the upper surface; they have an entire and partly revolute margin, and the venation is distinct and finely reticulate. Very young leaves are pubescent, the unicellular covering trichomes being thick-walled and mostly curved.
• Taste: Astringent, slightly bitter.
• Plant Source: Arctostaphylus uva-ursi
• Other Names: Arberry, Bearberry, Bear’s Grape
• Habitat: The plant has spread from the Iberian Peninsula across Central Europe north to Scandinavia and east to Siberia. The plant is found also in the Altai Mountains. The Himalayas and North America.
• Family: Ericacea
Simple Phenol-containing Drugs
Drug Name: Uvae ursi Folium
Simple Phenol-containing Drugs
Drug Name: Uvae ursi Folium
Constituents:
a. Hydroquinone glycosides:
Arbutin (arbutoside, hydroquinone-O-b-D-glucoside, 5-16%)
Methylarbutin (O-methylhydroquinone-O-b-D-glucoside, up to 4%)
Galloil derivatives of arbutin (0.05%)
Free hydroquinone (usually under 0.3%)
b. Phenyl carboxylic acids:
Gallic acid (free 180mg/100g) -p-Coumaric acid (18.0mg/100g)
Syringic acid (16.8mg/100g)- Salicylic acid (12.0mg/100g)
p-Hydroxybenzoic acid (9.6mg/100g) - ArbutinHydroquinone
Ferulic acid (6.0mg/100g) -Caffeic acid (6.0mg/100g)
Lithospermic acid (dimeric caffeic acid)
c. Tannins-d. Iridoide- e. Flavonoids-f. Triterpenes
Simple Phenol-containing Drugs
Drug Name: Uvae ursi FoliumEffects:The tannins in Uva-Ursi act as an astringent, and the phenol glucosides and their aglyca have antibacterial effect. The antimicrobial effect is associated with the aglycon hydroquinone released from arbutin or arbutin waste products in the alkaline urine. The drug has urine-sterilizing properties that are attributed to bacteriostatic hydroquinones, conjugates of glucuronic acid and sulfuric acid. The maximum antibacterial effect is expected 3 to 4 hours after administration. There are no clinical studies available that have been definitively evaluated.
Indications and Usage:
Infections of the urinary tract
Uva-Ursi is used for inflammatory disorders of the efferent urinary tract.
Contraindications: The drug is contraindicated in pregnant women,
nursing mother and children under 12 years of age.
Precautions and Adverse Reactions: General: No health hazards are known in conjunction with the proper administration of designated therapeutic dosages. Individuals with gastric sensitivity may experience nausea and vomiting following intake the preparation made from the drug due to it high tannin content.
Simple Phenol-containing Drugs
Drug Name: Uvae ursi Folium
Pregnancy: The drug is contraindicated during pregnancy.Nursing mothers: The drug is contraindicated in nursing mothers.Pediatric Use: Liver damage is conceivable in connection with administration of the drug over extended periods, particularly with children, due to the possible hepatotoxicity of the hydroquinones released. The drug is contraindicated in children less than 12 years of age.
Drug Interactions:Uva-Ursi preparations should not be administered with any substance causing acidic urine since this reduces the antibacterial effect. Because the urine-disinfecting effects of the hydroquinone released in the urinary tract only occurs in an alkali environment, the simultaneous administration of medication or food that increase uric acid levels in the bladder is to be avoided.The sodium sparing effect of Uva-Ursi may offset the diuretic effect of Thiazide and loop diuretics.Uva-Ursi may add to the gastrointestinal irritation that occurs with NSAID use
Over dosage:
-Over dosage may be lead to inflammation and irritation of the bladder and urinary tract
mucous membranes.
-Liver damage is conceivable in connection with administration of the drug over extended
periods, particularly with children, due to possible hepatotoxicity of the hydroquinones
released
Drug Name: Folia Cynarae
Description: Prickly pinnate to double pinnate leaves.
The upper surface is bare and light green; the lower
surface is gray and tomentose.
Plant Source: Cynara scolymus
Other Names: Artichcoke
Habitat: The plant is found in the Miditerranean region,
the Canary Islands and South America. It is
cultivated elsewhere.
Family: Asteraceae
Phenolic Acid-containing Drugs
A. Caffeic Acid Derivative-containing Drugs
Constituents:a. Caffeic Acid Derivatives: Chlorogenic Acid, Neochlorogenic Acid,Cryptochlorogenic Acid Cynarin
b. Flavonoids (0.5%): in particular rutinc. Sesqiterpene Lactones (0 to 4%)
Folia Cynarae
Phenolic Acid-containing Drugs
A. Caffeic Acid Derivative-containing Drugs
Folia Cynarae
Effects:The main active principles are sesquiterpenes, hydroxy cinnamic acid and flavonoids. The drug has a cholagogic, hepatotoxic and lipid-reducing effect. A choleretic effect has been observed in rats (effect of cinnamic acid). The cholestrol level were reduced in the rats; a hepatostimulating and bitter effect on the gastrointestinal tract has also been documented.
Indications and Usage:
Liver and gallbladder complaints, Loss of appetite.
Contraindications: Because of the stimulating effect of
the drug upon the biliary tract, it should not be
administered if there is a bile duct blockage. Colic can
occur where the patient suffers from gallstones.
Phenolic Acid-containing Drugs
A. Caffeic Acid Derivative-containing Drugs
Folia Cynarae
Precautions and Adverse Reactions:
-Health risk or side effects following the proper administration of designated therapeutic dosages are not recorded.
-The plant possesses a medium potential for sensitization through skin contact.--Allergic reaction occur in particular when there is frequent on-the-job contact with artichokes. -There are cross-reactions with other composites (including chrysanthemes, arnica pyrethr
Phenolic Acid-containing Drugs
A. Caffeic Acid Derivative-containing Drugs
Rosmarini Folium
Drug Name: Rosmarini FoliumDescription: The up to 3cm long and up to 4mm wide leaves are narrowly lanceolate, sessile, leathery and very brittle, and with a revolute margin (upper row). Young leaves are pubescent on the upper surface, while older leaves are glabrous. They are wrinkled and gooved because of the sunken midrib which projects conspicuously from the densely woolly lower surface.Odour: Spicy and harsh, almost camphor-like.Taste: Spicy and harsh, bitter and aromatic, some what pungent.Plant Source: Rosmarinus officinalis L.Other Names: RosemaryHabitat: The plant is indigenous to the Mediterranean region and Portugal and is cultivated there as well as on the Crimea, in the Transcaucasus, Central Asia, India, Southeast Asia, South Africa, Australia and the U.S.Family: Lamiaceae
Constituents:
a. Caffeic acid derivatives: chief component rosmarinic
acid
b. Diterpenes, c. Flavonoids,d. Triterpenes,e.Volatile oil
Phenolic Acid-containing Drugs
A. Caffeic Acid Derivative-containing Drugs
Rosmarini Folium
Effects: The drug is mildly antimicrobial and antiviral (probably because of the diterpenes).
- Animal tests have demonstrated spasmolytic effects on gallbladder ducts and on the upper intestine.
-The tests have confirmed choleretic, liver-protective, anti-convulsive, antimutagenic and tumor-inhibiting effects.
-The metabolism of the drug is accelerated by the presence of 1,8 cineol.
-In humans Rosemary oil improves circulation when applied externally because of a certain skin irritating effect.
Indications and Usage: Approved by Commission E:
Blood pressure problems-Dyspeptic complaints
Loss of appetite –Rheumatism
Rosemary is used for dyspeptic disorders and externally for hypotonic circulatory
disorders and rheumatic conditions.
Phenolic Acid-containing Drugs
A. Caffeic Acid Derivative-containing Drugs
Rosmarini Folium
Contraindications: Rosemary preparations should not be used during pregnancy.
Precautions and Adverse Reactions: General: No health hazards or side effects are known in the conjunction with the proper administration of designated therapeutic dosages. Contact allergies have been observed on occasion.
Pregnancy: Not to be used during pregnancy.
Over dosage: Very large quantities of rosemary leaves misused for the purpose of abortion, can lead to deep coma, spasm, vomiting, gastroenteritis, uterine bleeding, kidney irritation, and to death in humans.
Phenolic Acid-containing Drugs
A. Caffeic Acid Derivative-containing Drugs
Salicis Cortex
Drug Name: Salicis CortexDescription: The 1-2 mm thick, quite often channeled pieces of bark have a glossy, greenish yellow or brownish gray outer Taste: Astringent and bitter.Plant Source: Salix alba L.Other Names: Willow, White WillowHabitat: The plant is indigenous to central and southern Europe.Family: Salicaceae
Constituents:
a. Glycoside and esters yielding salicylic (1.5-12%):
Salicin (0.1-2%)- Salicortin (0.01-11%)
Salicin derivatives acylated to the glucose residue (up to
6%, including among others, fragilin, populin)
b. Tannins (8-20%) c. Flavonoid
Phenolic Acid-containing Drugs
A. Caffeic Acid Derivative-containing Drugs
Salicis Cortex
Effects:The efficacy of the drug is due mainly to the proportion of salicin present. After splitting of the acyl residue, the salicin glycosides convert to salicin, the precursor of salicylic acid. Salicylic acid is antipyretic, antiphlogistic and analgesic. White willow bark is the phytotherapeutic precursor to acetylsalicylic acid (aspirin).The salicin component is responsible for anti-inflammatory and antipyretic effects. The tannin cont
Indications and Usage: Approved by Commission E:RheumatismPainSalicin is useful in diseases accompanied by fever, rheumatic ailments, headaches and pain caused by inflammation.Contraindications: Willow bark is contraindicated in patients that have a hypersensitivity to salicylates. Salicylates should not be used in children with flu-like symptoms due to the association of salicylates with Reyes Syndrome
Phenolic Acid-containing Drugs
A. Caffeic Acid Derivative-containing Drugs
Salicis Cortex
Precautions and Adverse Reactions:General: No health hazards are known in conjunction with the proper administration of designated therapeutic dosages. Stomach complaints could occur as a side effect due to the tannin content.Pregnancy: Salicylats should be avoided during pregnancy.Nursing mothers: Salicylates have been associated with rashes in breast-fed infants; use is not recomended.
Drug Interactions:
- Due to the salicin component, caution should be exercised when used in combination with salicylates
and other NSAID.
Though there are no reports of interactions with drugs that affect blood clotting times, and some studies
suggest that thrombocyte inhibition is unlikely.
Anti-platelat medications and any medication that prolongs the PT time should not be used with
Willow bark.
Alcohol and Barbiturates may mask the symptoms of salicylate overdosage and may enhance the
toxicity of salicylates.
There have been reports of metabolic acidosis in children with normal renal and hepatic functions that
were treated with salicylates and carbonic anhydrase inhibitors for joint pain and glaucoma. This
combination should be avoided.
Phenolic Acid-containing Drugs
A. Caffeic Acid Derivative-containing Drugs
Drug Name: Curcumae longae RhizomaOdour: Faintly aromatic and spicyTaste: Pungent and bitter.Plant Source: Curcuma domestica VALETONOther Names: TumericHabitat: Tumeric is indigenous to India; it is cultivated today in India and other tropical regions of Southeast Asia.Family: Zingiberaceae
Curcumae longae Rhizoma
Constituents:a. Curcuminoids (3-5%): Curcumin ,Desmethoxy curcumin, Dihydrocurcuminb. Volatile oil (3-5%) ,c. Starch (30-40%)d. 1,5-diaryl-penta-1,4-dien-3-one derivatives
Phenolic Acid-containing Drugs
A. Caffeic Acid Derivative-containing Drugs
Curcumae longae Rhizoma
Effects: Tumeric has -antihepatotoxic, antihyperlipidemic and anti-inflammatory effects.- It is also antioxidative (inhibit lipid peroxide formation in the liver),-antitumoral and antimicrobial (in particulat sesquiterpene derivatives).- It has insect repellent and antifertile effects.-It also inhibits prostaglandin formation, in vitro.Indications and Usage: Approved by Commission E:Dyspeptic complaints -Loss of appetite
Contraindications:General: People with obstructed biliary ducts should not use the drug; those with gallstones should take it only under the supervision of a physician.Pregnancy: Tumeric should not be used during pregnancy.
Precautions and Adverse Reactions:Health risks or side effects following the proper administration of designated therapeutic dosages are not recorded. Stomach complaints can occur following extended use or in the case of overdose
Phenolic Acid-containing Drugs
A. Caffeic Acid Derivative-containing Drugs
Drug Name: Zingiberis RhizomaOdour: Characteristic, aromatic.Taste: Pungent and spicy.Plant Source: Zingiber officinale ROSCOEOther Names: GingerHabitat: indigenous to southern eastern Asia, and is cultivated in the U.S., India, China, West Indies and tropical regions.Family: Zingiberacea
Zingiberis Rhizo
Constituents:a. Aryl alkanes: Gingerols: chief components [6]-gingerol (pungent
substances), [8]-gingerol, [10]-gingerolShogaols: chief components [6]-shogaol (pungent
substance), [8]-shogaol, [10]-shogaol (artifacts formed during storage, arising from gingerols)
b. Diarylheptanoids: Gingerenone A and B - c. Volatile oil (2.5-3%) d. Starch (50%)
Phenolic Acid-containing Drugs
A. Caffeic Acid Derivative-containing Drugs
Zingiberis Rhizo
Effects: studies show that
-Ginger root is positively inotropic,
- antithrombotic; has anti-oxidant, anti-migraine
-anti-lipidemic effects, promotes secretion of saliva, gastric
juices and bile.
Anti-Emetic Effects: The components in Ginger that are responsible for the anti-emetic effect is thought to be the gingerols and shogaols. -The mechanism of action is not due to a nystagmus response or vestibular stimulation. -In contrast to most anti-emetic medications that act on the CNS, the anti-emetic effect of Ginger is thought to be due to local gastrointestinal actions
Anti-Inflammatory Effects: The anti-inflammatory effect of Ginger is
thought to be due to inhibition of cyclooxygenase and 5-lipoxygenase,
results in reduced leukotriene and prostaglandin synthesis.
Phenolic Acid-containing Drugs
A. Caffeic Acid Derivative-containing DrugsZingiberis Rhizo
Miscellaneous Effects: In humans,-Ginger increases the tone and peristalsis of the intestine. -The root of Zingiber officinale has also shown immune system stimulation and platelet aggregation inhibitory activ
Indications and Usage: Approved by Commission E:
Loss of appetite -Travel sickness-Dyspeptic complaints
Contraindications:-contraindicates the use of Ginger in morning sickness associated with pregnancy.-can be used and is effective in the treatment of morning sickness.-It is recommended that excessive doses be avoided for this purpose. Because of its cholagogic effect, the drug should not be taken in the presence of gallstone conditions except after consultation with a physician.-inhibit thromboxane synthesis; therefore patients who are at risk for hemorrhage should not use it.Over dosage:- LD50 of 6-gingerol and 6-shoagol is set between 250 and 680 mg/kg.- Toxicity tests in mice using a Ginger extract via lavage resulted in no mortality or adverse effects in doses up to 2.5 g/kg over a 7 days period.- When the dose was increased to between 3 and 3.5 g/kg, a 10% to 30% mortality rate was reported.Over dosage may cause cardiac arrhythmia and CNS depression.
Phenolic Acid-containing Drugs
A. Caffeic Acid Derivative-containing Drugs
Zingiberis Rhizo
Precautions and Adverse Reactions: General:No health hazards are known in conjunction with the proper administration of designated therapeutic dosages.administration of 6 grams of dried powdered Ginger has been shown to increase the exfoliation of gastric surface epithelial cells in human subjects.It is postulated that this action may possibly lead to ulcer formation.Therefore, it is recommended that dosages on an empty stomach be limited to 6 grams.There have been reports that Ginger can cause hypersensitivity reactions resulting in dermatitis. Large overdoses can cause central nervous system depression and cardiac arrhythmias.
Pregnancy:pregnant patients with hyperemesis gravidarum (persistent vomiting occurring prior to the 20th week of pregnancy and requiring hospitalization) found that 1 gram per day (250 milligram 4 times a day) for 4 days caused no adverse effects. One spontaneous abortion occurred: a casual relationship between the abortion and the use of Ginger was not determined. All infants were normal.Drug Interactions:-More than one in-vitro study confirms antithrombotic effect. -It is recommended that patients taking anticoagulants or those with bleeding disorders avoid the use of large doses of Ginge
Phenolic Acid-containing Drugs
Kava Kava
Styrylpyrones
Drug Name: Kava Kava
Plant Source: Piper methysticum
Other Names: Kava Kava
Habitat: The plant is indigenous to the
South Sea Islands and mainly cultivated
there.
Family: Piperaceae
Constituents:
a. Kava lactones (kava pyrones, 5-
12%):
(+)-kavain, dihydrokavain (marindinine)
(+)-methysticin ,dihydromethysticin,
yangonine,desmethoxy-yangonine
b. Chalcones: including flavokavin A
and B
Phenolic Acid-containing Drugs
Kava Kava
Styrylpyrones
Effects:have centrally muscle-relaxing, anticonvulsive and antispasmodic effects. The herb also contains hypnotic/sedative, analgesic and psychotropic properties contributing to its use for anxiety and insomnia.The centrally muscle-relaxing, analgesic and anticonvulsive action of the kava pyrones, kavain, dihydrokavain, dihydromethysticin and (+/-) kavain (synthetic kava pyrone) attributed to the interaction with ion channels
The interaction consists of fast and specific inhibition of voltage-dependent sodium channels and reduction of currents through voltage activated sodium and calcium channels.The paralysis effect of Kava on neuromuscular transmission and muscle contractility is similar to that of local anesthetics. The lipid soluble extract (kava resin) decreases spontaneous motility and motor control.
Phenolic Acid-containing Drugs
Kava Kava
Styrylpyrones
The analgesic action of kavain, dihydrokavain,
methysticin and dihydromethisticin to
antinociceptive activities.
Nalaxone (opiate antagonist) is ineffective in
reversing the antinociceptive activities, thus
indicating the analgesia produced from the
compounds occurred via non-opiate pathways.
The lipid soluble components of kava don’t interact with benzodiazepine binding sites, but do seem to potentiate the activity of GABA-A in the brain center for sedative effects.The psychotropic properties of Kava have been demonstrated by inhibition of norepinephrine uptake by kavain, dihydromethysticin and the racemate (+/-) kavain. One study did find that desmethoxyyangonin, methysticin, yangonin, dihydromethisticin,dihydrokavain and kavain reversibly inhibit MAO-B. An increase of dopamine and serotonin by activation of neurons results in central nervous system effect
Phenolic Acid-containing Drugs
Kava Kava
Styrylpyrones
A recent study investigated the antithrombotic activity of kava pyrones. Kavain exert antithrombotic action on human platelets through the inhibition of cyclooxygenase (COX) as a primary target.
This suppresses the generation of thromboxane (TXA2), which normally induces aggregation of platelets and exocytosisi of ATP by its binding on TXA2 receptors
Indications and Usage:
-Nervousness and insomnia
Contraindications:
-The drug is contraindicated in patients with endogenous depression
because it increases the danger of suicide.
-It is also contraindicated during pregnancy and in nursing mother
Phenolic Acid-containing Drugs
Kava Kava
Styrylpyrones
Precautions and Adverse Reactions: General: No health hazards are known in conjunction with the proper administration of designated therapeutic dosages.Administration of the herb leads to rare cases of allergic reactions and gastrointestinal complaints. Slight morning tiredness can appear at the beginning of the therapy. Motor reflexes and judgment when driving may be reduced while taking the herb
Central Nervous System: Dyskinesia and choreoathetosis of the limbs,
trunk, nick and facial musculature have been reported secondary to the
administration of kava.
Endocrine: Following long-term use of high doses of Kava extract,
weight loss was reported.
Phenolic Acid-containing Drugs
Kava Kava
Styrylpyrones
Hepatotoxicity:
Increase in gamma-glutamyl transferase (GGT)
levels have been associated with high doses of
Kava extract.
Two cases of acute hepatitis with an increase of
liver enzymes were reported.
Necrotizing hepatitis was determined after a
liver biobsy, and upon discontinuation of Kava,
liver tests normalized
Musculoskeletol: Minor inhibition of movements and impaired motor reflexes have
been observed with the use of Kava.
Ocular: Increase in pupil diameter, reduction of the near point of accommodation
and near point of convergence, and disturbance to the oculomotor balance have been
reported with Kava.
Eye irritation has been reported with the heavy consumption of Kava.
Phenolic Acid-containing Drugs
Kava Kava
Styrylpyrones
Skin:
Heavy chronic consumption of Kava is associated with a
peculiar, scaly rash suggestive of ichthyosis.
A reversible, slight yellowing of the skin has been associated
with long-term use of Kava.
Sebotropic drug reactions resulting from kava-kava extract
therapy has been reported.
The drug shouldnot be taken for longer than three months
without a doctor’s supervision.
Drug Interactions: Alcohol- concomitant use of kava kava with alcohol results in an increase in each other’s hypnotic action. The alcohol also increases the possibility of kava toxicity.Alprazolam- Kava used simultaneously with alprazolam has resulted in coma.CNS depressants such as barbiturates- The herb may be potentiate the effectiveness of substances that act on the central nervous system.
Phenolic Acid-containing Drugs
Kava Kava
Styrylpyrones
Psychoactive agents- The intensity of psychoactive agents may be intensified with kava.Dopamine- Kava Kava has been reported to antagonize the effect of dopamine. Patients with Parkinson’s disease taking levadopa should avoid the use of the herb.
Pregnancy: The drug is contraindicated during pregnancy.Nursing Mothers: The drug is contraindicated in nursing mothers
Over dosage: Over dosage can result in disorders of
complex movement, accompanied by undisturbed
consciousness, later tiredness and tendency to sleep
Drug Name: Resina Podophylli
Plant Source: Podophyllum peltatum
Other Names: May apple, Mandrake
Habitat: The plant is indigenous to northeast
North America
Family: Berberidacea
Drugs Containing Lignans And Related
Compounds
Resina Podoph
Constituents:-Podophyllin (3-6% resin, mixture of ethanol-soluble extractive martial from the root), The main constituents of the resin are aryltetrahydronaphthalenes:-Podophyllotoxin (20%), a- & b-peltatin (5% and 10% respectively), 4’-dimethyl podophyllotoxin,
desoxypodophyllotoxin
O
O
O
OH
OCH3
OCH3H3CO
O
Podophyllotoxin
O
O
O
R
OCH3H3CO
O
OH
R= -OH a-Peltatin
R= - OCH3 b-Peltatin
Drugs Containing Lignans And Related
Compounds
Resina Podoph
O
O
O
OH
OCH3
OCH3H3CO
O
Podophyllotoxin
O
O
O
R
OCH3H3CO
O
OH
R= -OH a-Peltatin
R= - OCH3 b-Peltatin
Effects: The drug is antimitotic.
Indications and Usage: Approved by Commission E:Warts
Contraindications: The drug is contraindicated in pregnancy
Precautions and Adverse Reactions: General: The drug is severely irritating to skin and mucous membranes. External administration of the drug over large skin areas can also bring about resorptive poisoning.
The drug should not be taken internally in allopathic medicine.With external use, the skin area to be treated should not exceed 25 sq. cm.
The drug serves as an industrial drug for the extraction of podophyllotoxin and its semi-synthetic derivatives that are used in tumor therapy.
Use in Pregnancy: The drug is contraindicated in pregna
Drugs Containing Lignans And Related
Compounds
Resina Podoph
O
O
O
OH
OCH3
OCH3H3CO
O
Podophyllotoxin
O
O
O
R
OCH3H3CO
O
OH
R= -OH a-Peltatin
R= - OCH3 b-Peltatin
Over dosage:
In dosages over 0.2 gm, it causes severe abdominal pain, bloody-watery diarrhea, vomiting of liquid bile, dizziness, headache, coordination disorders, spasm, nephritis, later collapse and death in coma through respiratory failure.
Following gastrointestinal emptying (inducement of vomiting, gastric lavage with burgundy-colored potassium permanganate solution, sodium sulfate)
electrolyte substitution and treating possible cases of acidosis with sodium bicarbonate infusions.
In case of shock, plasma volume expanders should be used. Monitoring of kidney function is essential.Intubations and oxygen respiration may also be necessary.
