Pharmacology Final Botanical Medicine

8/2/2019 Pharmacology Final Botanical Medicine

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Dr Leonie Curtolo


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No direct function on growth and development

= Secondary metabolites, secondary products or naturalproducts

Primary metabolites:

Chlorophyll, amino acids, nucleotides, simple carbohydrates ormembrane lipids

Recognized roles in photosynthesis, respiration, solute transport,translocation, nutrient assimilation and differentiation

Throughout plant kingdom

Secondary metabolites:

Restricted distribution in plant kingdom

Certain only found in one plant species / taxonomically related

group of species


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Funtions:

1. Defends plants against being eaten by Herbivores andinfection by pathogens

2. Plant defenses evolved to maintain reproductive fitness Evolution of metabolites lead to greater reproductive fitness than

undefended plants as long as the metabolic cost of producing them wasnot excessive

Defended plants left more descendant than undefended ones and passedtheir defensive traits on to the next generation.

Interesting that defense compounds to increase reproductive fitness bywarding off fungi, bacteria and herbivores also make them undesirable asfood for humans. Certain crops artificially selected to for producing lowlevels of compounds, can make them more susceptible to insects anddisease and leads to more chemicals being used to protect crops


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Three principle groups of secondary metabolites:

1. Nitrogen-containing 2nd ary productsAlkaloids, biosynthesized from amino acids

2. Phenolic compounds:

Aromatic substances, via shikimic acid pathway or malonic acid

pathway

3. Terpenes:

lipid synthesized, from acetyl CoA or basic intermediates of

glycolysis


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5major subclasses: monoterpenes, sesquiterpenes,diterpense, triterpenes and polyterpenes

Synthesized from IPP (Isopentenyl pyrophosphate) andDMAPP (Dimethyallyl pyrophosphate)


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Monoterpenes (C10):

Important agents of insect toxicity

Plants contain mixtures of volatile monoterpenes and sesquiterpenes =ESSENTIAL OILS

Lamiaceae family: peppermint (monoterpene = menthol), lemon(monoterpene = limonene), basil and sage

Conifers (f.e. pine and fir): Resin monoterpenes accumulate in resinducts in needles, twigs and trunks = -pinene, B-pinene, limonene andmyrcene

Toxic to insects and beetles

Found in glandular hair on epidermis advertise toxicity of plant,repelling insects and other herbivores

Essential oils: extracted via steam distillation (commercially used toflavour foods and making perfumes)


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S

esquiterpene lactones (C15): Compositae family

Glandular hair

Characterized by lactone ring (cyclic ester)

Feeding repellants to herbivores and mammals = taste BITTER

Solanaceae


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Diterpenes (C20)

Toxins and feeding detergants

Resins, from pines and tropical leguminous trees contain abieticacid

Euphorbiaceae (Spurge family): diterpene esters of phorbol

When resins canals are pierced by insect feeding the outflow of

resin may physically block feeding and serve and chemicaldeterrent to continued predation

Phorbol type diterpenes tumor promoters in animals

Pacific yew (Taxus brevifolia) contain taxol anti-cancer drug

Abieticacid

Phorbol


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Triterpenes (C30)

Steroids

Found in plasma membranes

Phytoecdysones by insects disrupts molting and other

developmental processes often with lethal consequences Limonoids:

Bitter substances in citrus spp.

Most powerful deterrent to insect feeding from Neem tree(Azadirachta indica) from Africa or Asia


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Triterpenes (C30)

Cardenolides

Glycosides (compounds containing an attached sugar)

Bitter tasting extremely toxic to higher animals

Humans: dramatic effects on the heart muscle (influence onNa+/K+activated ATPases); regulated doses they strengthen the heartbeat.

Foxglove (Digitalis) cardenolides extracted to treat heart disease Digitoxigenin (aglycone sugarless triterpene portion of

naturally occuring digitanides)

Glycosides aglycone + sugar


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Triterpenes (C30)

Saponins Steroids and tripterpene glycosides

Soaplike properties: soapy lather when shaken with water

Both lipid-soluble (triterpene) and water-soluble (sugar) elemens inone molecule gives saponins detergent properties

Toxicity due to ability to form complexes with sterols

May interfere with sterol uptake from the digestive system or disruptcell membranes after absorption into bloodstream

Yam (Dioscorea villosa)

Yamogenin

Used as starting materials in synthesis of progesterone like compounds forbirth control pills.


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Polyterpenes ((C5)n)

rubber


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Functions:

1. Defense mechanisms2. Mechanical support in attracting pollinators and fruit

dispersers

3. Absorbing harmful ultraviolet radiation

4. Reducing the growth of nearby competing plants Synthesized from 2 different pathways

Shikimic acid pathway

COH converted to aromatic amino acids

In plants, fungi and bacteria but not animals

Phenylalanine Cinnamic acid Simple phenolics / lignin /flavonoids / condensed tannins

Phenylalanine ammonia lyase (PAL) catalyses formation ofphenylalanine to cinnamic acid activity increased by environmentalfactors, such as low nutrient levels, light, and fungal infection.

Malonic pathway


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Simple

Phenolic

Compounds

Furanocoumarins non toxic until activated by UV-ligth /sunlight.

Activated furanocoumarins insert themselves into double helixDNA bind to pyrimidine bases cytosine and thymine blockingtranscription and repair leading to cell death Umbelliferae (cellery, parsnip and cellery)

Allelopathic activity (inhibiting growth of other plants: cafeicacid and ferrulic acid From leaves roots and decaying litter release substances into

enviroment

Lignin: primary and secondary roles Most abundant after cellulose

Strengthening Bonds to cellulose and protein, reduces digestibility Blocks growth of pathogens and response to infection or

wounding


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Flavonoids Largest class of plant phenolics

15 carbons in a arrangement with 2 aromatic ringsconnected by a 3 carbon bridge

Fusion of 2 parts synthesized from 2 different pathways shikimic acid pathway and the malonic acid pathway

Anthocyanins Coloured flavonoids that attract animals for pollination and

seed dispersal (mutualism)

1 of 2 principles colored pigments flavonoids (othercarotenoids terpenoid compound accessory compounds inphotosynthesis yellow, orange and red)

Red, pink, purple, blue colors in plants

Anthocyanin anthocyanidins + sugars


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Anthocyanins Anthocyanidins:

Pelargonidin (organge red)

Cyanidin (Purplish red)

Delphinidin (Bluish purple)

Peonidin (Rosy red)

Petunidin (purple)

Anthocyanins and carotenoids responsible for variety ofcolours in plant kingdom.

Colour one type of signal to animal also monoterpenesprovide attractive scents.


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F

lavones and flavonols Absorb light at shorter wavelengths, not visible to human

eye

Visible to bees and insects may indicate the location ofpollen and nectar


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Isoflavonoids

Defense compounds synthesized immediately following infection byfungi or bacteria

Leguminosae

Tannins

Plant phenolic polymer

1st used to describe compounds that could convert raw animal hidesinto leather in the process known as tanning

Tannins bind to collagen proteins of animal hides, increasing resistanceto heat, water and microbes

2 categories:


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Tannins

1. Condensed tannins

2. Hydrolyzable tannins

Astringents taste due to binding of salivary proteins

General toxins that reduce growth and survivorship, most mammalsavoid, but humans often prefer certain level of astringency in tannincontaining foods apples, blackberries, tea and red wine

Inactivate herbivore digestive enzymes and create complexaggregates of tannins and plant proteins that are difficult to digest


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Nitrogen in structure

Alkaloids Poisonous if taken in sufficient quantity

Strychnine, atropine, coniine (poison hemlock)

Lower doses useful pharmacologically

Morphine, codeine, atropine and ephedrine Stimulants or sedatives

Cocaine, nicotine and caffeine

Mechanism of action:

1. Interfere with components of the NS, esp. chemicaltransmitters

2. Others affect membrane transport, protein, or miscellaneousenzyme activities


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Cyanogenic glycosides

Release poison hydrogen cyanide

Glucosinolates (mustard oil glycosides)

Also release volatile toxins

Cruciferae


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bitter principles release of gastrin

Release of gastrin increases: Gastric acid & pepsin secretions

Pancreatic digestive secretions

Intestinal juice production

Hepatic bile flow Hepatic bicarbonate production

Brunners glands secretions

Intrinsic factor secretinos insulin, glucagon & calcitonin

secretions Muscle tone of lower oesophageal sphincter

Muscle tone of stomach and small intestine

Cell division & growth of gastric & duodenal mucosa

Cell division & growth of pancreas


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Indications :

Increase appetite and digestive secretions

Enable body to digest,

assimilate vital nutrients

Eliminate wastes efficiently

Food

= nourishment also present immunological challenge

Low stomach secretions

enteric infections

Antigen penetration through gut wall (f.e. dysbiosis - candida,food allergies)

Autoimmune problem coinciding with depressed digestion

Stimulate the totality of digestive activity


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Stimulate the totality of digestive activity Protect gut tissue

Promote bile flow

Enhance pancreatic function

Tonics Nervous disorders and emotional disharmony

Also,

Bitter tonics

Hepatics Choleretics (improves amounts of secretions)

Cholagogues (stimulates gallbladder contraction toimprove secretions)


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Compositae family Especially useful in hypercholesterolaemia

Cautions:

Allergy to Compositae family

Contact dermatitis not oral ingestions

Cholelithiasis (gallstones)


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Compositae family

Relates spp A. annua,A. afra,A abrotanum etc

Aromatic bitter

Dyspepsia

Safety:

Contra-indicated in pregnancy

No longer than 4-6 wks

High doses

CNS toxin cause hallucinations & addictions


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Mustard Oil Glycosides

G

lycosides / glucosilinates Cruciferae family

Mostly used externally as rubefacients (increases local bld flow) orvesicants

Goitrogenic (substances that suppress the function of the thyroid gland

by interfering with iodine uptake) if consumed in large amounts Miscellaneous Pungent Constituents

Pungent alkaloids: capsaicin (Capsicum spp)

Volatile oils (Zingiber off)

Sulphur-containing constituents (Allium spp)

Rubefacient, vesicant, counter-irritants (therapeutic inflammation,without destructive inflammatory agents)

Stimulate circulation at a local level

Stimulate stomach acid production

Carminative

Disinfects lungs and expectorates


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Mixture of fragrant compounds Extracted by steam distillation

Wide range of pharmacological activities

Antimicrobial and spasmolytic, carminative (mint, sage,rosemary, cardamon, dill), diuretics (juniper), expectorant(aniseed), sedative (lavender), anxiolytic (melissa),anaesthetic (clove), analgesic (lemongrass), rosemary(stimulant activity), diaphoretic, anti-inflammatory, anti-

ulcer and oestrogenic activities


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Tea tree

Chamomile

Lemon balm

Buchu


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Plant pigments Flavus = pigment

Anti-oxidant activity, reducing capillary fragilityand permeability, duiretcs, anti-spasomodic, anti-inflammatory, antiseptic

Yarrow

Elder


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Resins (Pinus spp), oleo-resins (Pinus spp),Oleo-gum-resins and gum resins (Commiphoramolmol, Boswelia spp), balsamic resins (Styrax

spp) and balsams (Myroxylon pereira) Uses: antiseptic, anti-inflammatory

Commiphora molmol

Potentilla erecta


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Treating wounds and burns

Haemostatics

Anti-inflammatory

Especially usefull in diarrhoea

Potentilla erecta


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Bulk laxatifes

Inflammations in the respiratory, urinary andGIT

Ulmusfulva


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Highly toxic cause lysis of bld cells Sapo = soap

Glycosides

On injections cause lysis of bld cells, haemolysis and are

highly toxic On oral ingestion hydrolysi occus splittin the glycosie into

its sugar and aglycone / sapogenin. Sapogenin does notposses the haemolytic properties and is safe.

2 classes:1. Steroidal saponins structural relationship to steroidal

hormones, cardioactive glycosides and vitamin D

Dioscin from Dioscorea villosa used to manufacture sex

hormones


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Triterpenoid saponins

Trigonella dioscin and diosgenine may also act as a precurosr tofemale hormones and adrenal hormones

Glycyrrhiza glabra saponins mimic adrenocorticotrophichomrone and potentiate glucocorticoid, prgesterone andaldosterone actigity by inhibiting their metabolism

Anti-inflammatory (Solidago candensis,stellaria media) Diuretic (Betula spp)

Antispasmodic (Nigella sativa)

Adaptogens (Glycyrrhiza glabra, panax ginseng)

Stimulating expectorants (Lobelia inflata, verbascu

m thapsu

s, Viola spp,Glycyrrhiza glabra)

Treatment of vascular disorders (Centella asiatica,Achilleamillefolium)

Used to increase bioavailability of other components

Facilitates absorption of nutrients.

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Pharmacology Final Botanical Medicine