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Pharmacognosy Plant Chemistry INTRODUCTION TO PHARMACOGNOSY Pharmacognosy knowledge of drugs and pharmaceuticals Greek: pharmakon (drugs) and gnosis (knowledge) BRIEF HISTORY Balonians made clay models of man Egyptians very apt in the practice of embalming Greeks Pedanios Dioscorides De materia medi...

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Pharmacognosy Plant Chemistry

INTRODUCTION TO PHARMACOGNOSY Pharmacognosy – knowledge of drugs and pharmaceuticals | Greek: pharmakon (drugs) and gnosis (knowledge)

BRIEF HISTORY Babylonians – made clay models of man Egyptians – very apt in the practice of embalming Greeks � Pedanios Dioscorides – De materia medica libre cinque (five volumes), 600 plants � (Rome) Galen – described the method of preparing formulas containing plant and animal drugs and the term ”Galenical pharmacy” originated (Cold cream – Galen’s cerate) Germans � C.A. Seydler – coined the term pharmacognosy in his dissertation in 1815 (title: Anaclectica pharmacognosthica) � Fluckiger –most comprehensive definition of pharmacognosy : “simultaneous application of various scientific disciplines with the object of acquiring knowledge of drugs from every point of view” � J.A. Schmidt – Lerbuch der Materia medica Pharmacognosy – “an applied science that deals with the biologic, biochemical and economic features of natural drugs and their constituents that originate in the plant and animal kingdom”

General Process of Extraction � Removes substances that can be dissolved by the solvent/menstruum � The undissolved portion of the drug is known as the marc � Product of extraction process: Percolate/Extractive

Crude Drugs – undergone only collection and drying Natural Substances – have not had changes made in their molecular structure as found in nature Derivatives/ Extractives – chief constituents obtained by extraction Geographic source & Habitat – region in which the plant or animal yielding the drug grows Indigenous – growing in their native countries Naturalized – growing in foreign land

PREPARATION OF DRUGS FOR THE COMMERCIAL MARKET 1. Collection – (small scale) collection time: part of the plant that constitutes the drug is highest in its content of AI 2. Harvesting – (large scale) � Mechanical devices : pickers, mowers, binders, swath, steel � Manual – for potent constituents 3. Drying (Air Drying and Artificial Air Drying) • remove moisture • fixes the constituents • prevent molding • facilitate grinding and milling • prevent action of bacteria • prevent environmental hydrolysis 4. Garbling – final stage; removal of extraneous matter (other parts of the plant, dirt, added adulterants) 5. Packaging, Storage and Preservation � To avoid insect attacks: a. SIMPLEST METHOD: Expose the drug to 65°C b. Fumigation with methyl bromide c. Add adrop of chloroform or carbon tetrachloride Collection time � Pectin – citrus fruits Unripe fruits - protopectin Just ripe - pectin Overripe - pectic acid � Marijuana

Young leaves - cannabidiol Mature leaves - cannabinol (THC) Appropriate Solvents: 1. Fats - Hexane 2. Resins - Alcohol 3. Chlorophyll - Acetone 4. Chrysarobin - Hot benzene

Examples of Plants in De Materia Medica Aloe Emollient, tx for burns Belladonna (beautiful lady) Atropine – mydriatic (SE: cycloplegia) Tamoxifen For breast CA (SE: endometrial CA) Colchicum Acute gout Allopurinol Chronic gout (Xanthine Oxidase inhibitor) Ergot (“fingers” Claviceps purpurea) Ergotamine (migraine), Ergonovine (oxytocic), LSD (hallucinogen) Opium (stone of immortality) Premarin Estrogen derivative from MARE Digoxin (Digitalis lanata) Digitoxin (Digitalis purpurea) Lipid soluble, Long half life

Street names of illegal drugs 1. Shabu Ice, Meth 2. Ecstacy Sky 3. Marijuana Hashish, MJ/Maryjane, Pot, Grass, Weed, Cannabis, Indian hemp

EVALUATION OF DRUGS (determine the quality (intrinsic property) and purity (absence of adulterants) of drugs) 1. Organoleptic - by means of the organs of sense; macroscopic appearance

2. Microscopic - essential in the study of adulterant in powdered plants (identity and purity) 3. Biologic - pharmacologic activity of certain drugs has been applied to their evaluation or standardization 4. Chemical - assay of AC using chemicals (titration); best method of determining official potency 5. Physical - physical constants (solubility, spec grav, optical rotation, congealing point, refractive index, MP) CLASSIFICATION OF DRUGS � Morphology – forms � Taxonomy – phylogeny (natural relationship or among plants and animals) � Pharmacologic or Therapeutic – based on effect on the body � Chemical classification – based on active constituents; Preferred Method of Classification

CHEMISTRY OF NATURAL DRUG PRODUCTS 1. Pharmaceutically active – cause chemical changes in the preparation 2. Pharmacologically active – responsible for the therapeutic activity 3. Inert constituents – no definite pharmacologic activity 4. Secondary plant substance – extracted, crystallized and purified; presence of inert matter which may modify or prevent absorbability or potency of AC Drug biosynthesis/Biogenesis – study of the biochemical pathways leading to formation of secondary constituents (drugs) Primary metabolites to Secondary metabolites Carbohydrates Glycosides BIOGENESIS Proteins OR Tannins

DRUG BIOSYNTHESIS

Fats Volatile oils or Fixed oils

3 Principal factors that influenced the secondary constituents of drug plants 1. heredity (genetic composition) 2. ontogeny (stage of development) 3. environment (soil, climate, associated flora and method of cultivation) Bioassay Digoxin - pigeon Atropine - cats Glucagon - cats Oxytocin - chicken (F) Head drop test - rabbits/rats PTH - dogs Heparin - sheep plasma Insulin - rabbit CARBOHYDRATES AND RELATED COMPOUNDS � polyhydroxyaldehydes or polyhydroxyketones containing C, H and O; same ratio as in H2O (2:1) � 1st products of photosynthesis (glucose) � General formula: CnH2nOn | Cn(H2O)n | (CH2O)n MONOSACCHARIDES Cannot be hydrolyzed to simple sugar substances that is ketonic or aldehydic substitution product of a polydroxy alcohol C Name Aldose Ketose 2 Diose Hydroxyacetaldehyde 3 Triose Glyceraldehyde Dihydroxyacetone 4 Tetrose Erythrose Erythrulose 5 Pentose Arabinose, Xylose, Ribose Ribulose 6 Hexose Glucose, Galactose Fructose 7 Heptose Sedoheptose 8 Octulose D-glycero-D-mannoctulose

HEXOSES (most important monosaccharides found in plants) Other names Uses Identification Test Glucose (aldohexose) D-glucose Dextrose Blood sugar Grape sugar Physiologic sugar Nutrient (parenteral), Excipient Ca gluconate/gluceptate/levulinate – Ca replenisher Ferrous gluconate – hematinic Moore’s Test (caramel) Fructose (ketohexose) Fruit sugar Levulose (sweetest monosaccharide) Food for diabetics Ingredient in infant feeding formula Ingredient in fructose injection, nutrient Seliwanoff’s Test

PENTOSES Xylose (D-xylose, Wood Sugar) � obtained by boiling corn cobs, straw or similar materials with dilute acid to hydrolyze the xylan polymer � diagnostic aid in intestinal malabsorption

OLIGOSACCHARIDES

DISACCHARIDES Other N Origin Uses Sucrose Glu + Fru (non-reducing) Saccharum Cane sugar Beet sugar Table sugar Saccharum officinarum (cane) Beta vulgaris (beets) Acer saccharum (maple) Demulcent, Sweetening, Coating, Preservative, Production of syrups, Retards oxidation Maltose Glu + Glu Malt sugar From germination of barley Lactose Glu + Gal (reducing) Milk sugar Cow’s milk (Bos Taurus) Isolation of Lactose Butter – cream, united fat globules Buttermilk – liquid separating from butter Skimmed milk – left after cream separates Cheese – coagulum, skimmed m. + rennin Whey – liquid separated from coagulum

CHO 4 cal/g CHON 4 cal/g Fats 9 cal/g Lactulose (Alkaline lactose) � lactic & acetic acid (irritation, catharsis) Dec serum NH3 in encephalopathy

POLYSACCHARIDES � Polysaccharides are polymers of monosaccharides (sugar) linked together through glycosidic(ether) linkages � Temporary storage form of photosynthetic products � systematic nomenclature are given the ending “an”, glycan is another word Amylose Amylopectin Linear Branched 250-300 glucose units 1000 or more glucose units 25% 75-80% α-1,4 glucosidic bonds α -1,4 and α-1,6 (every 25 glucose) Soluble Insoluble (paste forming) Blue Blue-violet or purple HOMOGLYCANS Use Starch (Glucosan) Zea mays (corn) Triticum aestivum (wheat) Solanum tuberosum (potato) Tablet filler, binder, and disintegrant Antidote for iodine poisoning Permanent reserve food material in plants

Gluten – tachy proteins Pregelatinized Starch – binder Na Starch Glycolate – disintegrant Hetastarch – plasma expander Enzymes that break down starches: β amylase – pancreatic juice and saliva α amylase – hydrolyzes it to maltose Starch Soluble starch Dextrin Maltose 2 glucose Inulin (Fructosan) Ingredient in culture media Used in evaluation of renal function Dextran (Glucosan) - plasma expander dextran sucrase (from Leuconostoc mesenteroides) Sucrose Dextran Cellulose Purified/Absorbent Cotton – from the hair of the seeds of Gossypium hirsutum Use: mechanical protection against bacteria; absorb mucus, pus, and blood Soluble guncotton/Pyroxylin – formed by action of nitric acid & sulfuric acid on cotton Other ingredients: Castor oil (flexibility) | Camphor (proof) Use: topical protectant Other derivatives: Cellulose Acetate Pthalate (CAP) – film coating, Methyl/Ethylcellulose HETEROGLYCANS (yield more than one type of monosaccharide units upon hydrolysis) Gums and Mucilages � Natural plant hydrocolloids that may be classified as anionic or non-ionic polysaccharides � Produced by plants as a protective after injury

� Upon hydrolysis, they yield arabinose, galactose, glucose, mannose, xylose, and other uronic acid derivatives � USES: suspending agents, dental adhesives, laxatives PLANT EXUDATES Tragacanth Best mucilage (resistant to acid hydrolysis) Astragalus gummifer Bassorin (swells) Tragacanthin (thickener) Suspending agent, Emulsifier, Adhesive, Demulcent, Emollient 5-6% dispersion in H2O Acacia Gum arabic Acacia senegal Arabin Incompatible with OH 35-36% dispersion Ghatti Indian Gum Anogeissus latifolia Acacia substitute Karaya (fetid odor) Sterculia Gum Sterculia urens D-galacturonic acid D-glucoronic acid Laxative, Suspending agent, Adhesive MARINE GUMS Agar Japanese Insinglas/Gelatin Gelidium cartilagineum (Red algae)

Agarose Agaropectin Laxative, tablet diluents/disintegrant Algin Macrocystis pyrifera (brown seaweed) Sodium alginate Suspending agent, tablet binder, thickener Carageenan Irish Moss, Chrondus Chondrus crispus Gigartina mamillosa Kappa- & Iotacarageenan (swelling) Lambda-carageenan (nonswelling) Demulcent, bulk laxative Danish agar Furcerallan Furcellaria fastigiata k-carrageenan Suspending agent SEED GUMS Plantago Psyllium, Plantain Seed Plantago psyllium (Spanish) P. ovate (Blonde/Indian) Bulk laxative Cydonium Quince seed Cydonia vulgaris Guar Gum Guaran Cymopsis tetragonolobus 1,4 linked Dmannopyranosyl Laxative, thickener, binder Locust Bean Gum

Carob pulp St. John’s bread Ceratonia siliqua Chocolate substitute MICROBIAL GUM Xanthan Gum Xanthomonas campestris Peudoplastic activity which enables toothpaste and ointment both to hold shape and spread readily PECTIN – purified carbohydrate product obtained from the dilute acid extract of inner portion of the rind of citrus fruits or from apple pomace Active Constituent : linear 1,4 linked D-galacturonan Uses : protectant, s.a., ingredient in many antidiarrheal formulations [O] � PLANT ACIDS a. Cherry Juice or Succus cerasi � Ripe fruit of Prunus cerasus � Contains pectin (incompatible with OH) � Constituent: Malic acid (present in cherry, apple, pear) � Use: preparation of cherry syrup b. Plant Acids Uses: Acidulants in effervescent formulations, Component of buffer systems a. Citric acid - (2-hydroxy 1,2,3, propane trioic acid) isolated by Scheele from lemon juice in 1784 b. Lactic acid - (alpha-hydroxy propionic acid) acidulant in infant feeding formula c. Tartaric acid - (1,2,3, dihydroxy butane dioic acid) by product of wine industry d. Fe fumarate - hematinic c. Alcohol or Ethanol � 95% ethanol by volume @15.56°C

� Product of fermentation � Undergo the process of distillation to concentrate the alcohol content to 40-55% brandy - distilled wine whiskey - malted grain rum - molasses wine - mild stimulant and tonic [H] � SUGAR ALCOHOLS � Mannitol (D-mannitol) � From Manna, Fraxinus ornus � Osmotic diuretic and Osmotic laxative � Sorbitol (D-glucitol) � From the ripe berries of mountain ash, Sorbus aucuparia � half as sweet as sucrose � has humectant properties (ingredient in toothpaste, chewing gums and various dietetic products) � not absorbed on oral ingestion that is why it is used in the manufacture of chewing gums TESTS FOR CARBOHYDRATES Test for Composition Positive result Molisch’s General for carbohydrates α-naphthol Purple/Red Fehling’s Reducing sugars A – CuSO4 B – K Na tartrate Brick red ppt Benedict’s Reducing sugars NaOH + CuSO4 Brick red ppt Barfoed’s Reducing sugars; Monosaccharides Cupric acetate + acetic acid Brick red ppt Tollen’s Reducing sugars (Aldehydes) Silver + Ammonia Silver mirror Picric acid Reducing sugars Picric acid Mahogany red Nylander’s Reducing sugars Na K tartrate + K/NaOH + Bi Brown Osazone/Kowarsky Mannose Phenylhydrazine Yellow ppt (ozone)

Seliwanoff’s Ketohexose (Fructose) Resorcinol Red Keller-Killiani Test Deoxysugars (cardiac glycosides) Acetic acid, Fe chloride, Sulfuric acid Reddish brown Moore’s Reducing sugars (Glucose) Heat with alkali Caramel Mucic acid Test Galactose Nitric acid Insoluble ppt Bial’s Pentoses Resorcinol + Fe Blue green

GLYCOSIDES � Heteroglycans (yield one ore more sugars among the products of hydrolysis); simple glycosides: sugar ethers � The most frequently occurring sugar is Beta-D-glucose (plants) � Aglycone or genin – nonsugar component, Glycone – sugar component

CARDIOACTIVE OR CARDIAC GLYCOSIDES MOA: inhibits Na/K/ATPase pump � increased influx of Ca2+ ions � (+) inotropy 2 types of steroidal aglycones or genin: � Cardenolides - most prevalent in nature � Bufadienolides - are homologs of the cardenolides and an unsaturated 6-membered lactone ring DOC: control rapid ventricular rate in px with atrial fibrillation/atrial flutter Keller-Killiani Test - Detects presence of 2-deoxysugars Other Names Origin Active Constituent Grecian Foxglove Digitalis lanata Digoxin Foxglove Digitalis purpurea Digitoxin (lipid soluble, long t½) Convallaria Lily-of-the-Valley Convallaria majalis Convallatoxin Adonis Pheasant’s eye Adonis vernalis Adonitoxin Strophanthus Strophanthus kombe k-strophanthoside/Strophanthidin Apocynum Black Indian Hemp Dog bane, Canadian Hemp Apocynum cannabinum Cymarin Oleander/Adelfa Rose bay Nerium oleander Oleandrin

Squill Urginea maritime Scillaren A Cactus Grandiflorus Night blooming cereus Selenicereus grandiflorus Black Hellebore Christmas rose Hellebborus niger hellebrin

ANTHRAQUINONE GLYCOSIDES Cathartics (except chrysarobin) Aglycone: Anthracene ID test: Borntrager’s test Origin Active Constituent Cascara Sagrada Sacred bark Rhamnus purchianus D glycosides – based on emodin C glycosides – based on aloin Cascarosides A&B – barbaloin isomers Cascarosides C&D – chrysaloin isomers Casanthranol – purified mixture of anthranol glycosides from cascara sagrada Frangula Buckthorn bark Rhamnus frangula Frangulin A & B Aloe Aloe barbadensis/Aloe vera (Curacao) A. ferox + africana + spicata (Cape) Barbaloin Aloe-emodin Rhubarb Rheum/Chinese Rhubarb Rheum officinale (Chinese)

R. emodi, R. webbianum (Indian/Himalayan) Rhein anthrones Senna Cultivated on wet lands resembling rice paddies Cassia angustifolia (Tinnevelly) Cassia acutifolia (Alexandria) Sennosides A, B, C, and D *More potent than cascara Chrysarobin Andira araroba (Goa powder; hot benzene) Keratolytic agent SAPONIN GLYCOSIDES β-hemolytic substances – destroys RBC by hemolysis and are toxic to cold blooded animals (used as fish poison) Soap-like (foam upon shaking) o Steroidal in nature (cyclopentanoperhydrophenanthrene/CPPP nucleus) o Sapotoxin – toxic aglycone o Sapogenin – aglycone portion, � 2 types: Steroid (neutral saponin) and Triterpenoid (acid saponin) Identification tests: 1. Froth test - (+) honeycomb froth that persists for 10 mins 2. Capillary test 3. BAM (Blood Agar Media) Test or Hemolysis Test α hemolysis – partial hemolysis β hemolysis – complete hemolysis γ hemolysis – no hemolysis Origin Active Constituent Use

Glycirrhiza Licorice root Glycyrrhiza glabra Glycyrrhizin/glycyrrhic acid (50x as sweet as sugar) Glycyrrhetic acid (anti-inflam) Peptic ulcer and Addison’s Increases foaminess of beer. CI: cardiac problems & HTN – ↑ Na retention and ↓K Ginseng • fave remedy in Chinese medicine Panax quinquefolius (American) Panax ginseng (Asian/Korean) Ginsenosides Panaxosides Chikusetsusaponins Aphrodisiac Adaptogen (antistress) Dioscorea Mexican Yam D. floribunda – best source of steroid D. spiculiflora – contains diosgenin Botogenin Diosgenin Cortisone precursor CYANOPHORE OR CYANOGENIC GLYCOSIDES (Bound Poisons) yeilds hydrocyanic acid as one of the products found in Rosaceae plants

amygdalin is the most widely distributed derivatives of mandelonitrile (benzaldehyde-cyanohydrin) Cyanide-containing compounds: Prunasin, Laetrile/Vitamin B17, Amygdalin Amygdalin Amygdalase *Amygdalase + Prunase = EMULSIN Mandelonitrile glucose Prunase Mandelonitrile + Glucose Benzaldehyde + HCN Origin Active Constituent Use Bitter Almonds Amygdalus communis Amygdalin Wild Cherry prunus virginiana, wild black cherry tree Prunus serotina Prunasin sedative expectorant Apricot Pits Prunus armeniaca, Rosaseae Laetrile/Vit. B17 controversial treatment for sickle cell anemia (antiCA) Cassava Manihot esculenta Mannihotoxin GLUCOSINATES/ISOTHIOCYANATES (From family Cruciferae/Brassicaceae) Black Mustard White mustard Synonym Sinapis nigra Sinapis alba Origin Brassica nigra Brassica alba Active Constituent Sinigrin myrosin Allyl isothiocyanate

Sinalbin myrosin Acrinyl isothiocyanate Uses Local irritant and emetic, Rubefacient, vesicant, and condiment FLAVONOL Rutin &Hisperidin Hesperitin & Naringen (Vitamin P or Permeability Factors) Tx of capillary bleeding secondary to capillary fragility Tx of symptoms of common colds ALCOHOL Salicin (Salix and Populus) Salix purpurea Salix fragilis Saligenin (salicyl alcohol) - antirheumatic (closely resembles salicylic acid) ALDEHYDE Vanilla Vanilla plantifolia Vanillin (4-hydroxy-3- methoxy benzaldehyde or methylprocatechuic aldehyde) Other sources of Vanillin: Coniferin - glycoside present in cambium sap of pine trees Eugenol - phenol present in clove oil Lignin - by product of the pulp industry Gluco-vanillin (avenein) and glucovanillic alcohol � hydrolyzed into glucose and vanillin and glucovanillic alcohol which is oxidized to vanillic

aldehyde PHENOL Uva Ursi (Bearberry) Arctotaphylos uvaursi Arbutin – antiseptic and astringent LACTONE GLYCOSIDES Origin Use Coumarin Dicumarol, Bishydroxycoumarin Dipteryx odorata (tonka beans) Anticoagulant Cantharides Spanish flies, Russian flies, Blistering flies Cantharis vesicatoria AC : Cantharidin Effects: � Blisters – irritant, vesicant, rubefacient � Priapism (used as aphrodisiac) Psoralens (photosensitizing furocoumarins) Ammi majus Methoxsalen – repigmentation in vitiligo Trioxsalen TANNINS � A group of complex phenolic compounds capable of combining with proteins � Polypeptides that are difficult to separate because they do not crystallize � Precipitates proteins from solutions and can combine with proteins, rendering resistant to proteolytic enzymes

� Product of fermentation � Undergo the process of distillation to concentrate the alcohol content to 40-55% brandy - distilled wine whiskey - malted grain rum - molasses wine - mild stimulant and tonic [H] � SUGAR ALCOHOLS � Mannitol (D-mannitol) � From Manna, Fraxinus ornus � Osmotic diuretic and Osmotic laxative � Sorbitol (D-glucitol) � From the ripe berries of mountain ash, Sorbus aucuparia � half as sweet as sucrose � has humectant properties (ingredient in toothpaste, chewing gums and various dietetic products) � not absorbed on oral ingestion that is why it is used in the manufacture of chewing gums

TESTS FOR CARBOHYDRATES Test for Composition Positive result Molisch’s General for carbohydrat...