INTRODUCTION TO PHARMACOGNOSY

A BRIEF HISTORY OF PHARMACOGNOSY

In 780 AD , a Greek pharmaco-botanist Pedanios Dioscorides wrote and described about 600 plants with medicinal properties in his book “De materia medica libre cinque(concerning medical matter in five volumes).

Galen was a Greek pharmacist-physician who lived in Rome and who describe the method of preparing formulas containing plant and animal drugs and the term ”galenical pharmacy” was originated.

In 19th century material medica (medical matter) undergo divisions:

1. pharmacology – the actions of drugs2. pharmacognosy – all aspects of drugs

with lesser emphasis on action

The word “pharmacognosy” formed from 2 Greek words pharmakon (drugs) and gnosis (knowledge) was introduced by C.A Seydler ( Chr. Aenotheus), a medical student in Halle/Saale, Germany who used the title Anaclectica pharmacognosthica for his dissertation in 1815

Fluckiger – presented the most comprehensive idea of the scope of Pharmacognosy which he define as the simultaneous application of various scientific disciplines with the object of acquiring knowledge of drugs.

Pharmacognosy may be defined as “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.

Recent historical research has found an earlier usage of “Pharmacognosis” in book der Materia medica published in Vienna in 1811which was published By J.A. Schmidt to describe the study of medicinal plants and properties.

In 19th century, chemist began to synthesize large number of organic compounds with structures of ever-increasing complexity, some of which were useful therapeutic agents. Thus there came 3 basic discipline devoted to drugs:

1. pharmacology which deals with drug actions and effects

2. pharmacognosy- covering all information on medicines from natural sources (plants, animals and microorganism

3. medicinal chemistry- the science of synthetic drugs

In the last decades of 29th century, 3 significant events occurred which have already produced

2. recognized the plants with reputation as remedies provide the best source of constituents that can serve as either as new drug or as prototype for them

3. greatest revolution which is still in its infancy as far as drug discovery is concerned is described as recombinant DNA technology, genetic engineering ormore specifically pharmacobiotechnology. which involves the transfer of geneticmaterial from one organism to another permitting the later to produce in quantitya component of the former that is useful as a drug.

VALUE OF NATURAL PRODUCTS:

Four significant roles of natural sources in modern medicine

1. they provide a number of extremely useful; drugs that are difficult to produce commercially by synthetic means. Examples: alkaloids of the opium poppy, ergot, solanaceous plants, cardiotonic glycosides, antibiotics, serum. Vaccines

2. natural sources also supply basic compounds that may be modified

slightly to render them more effective or less toxic. Examples : numerous variation of the morphine molecule

3. their utility as prototypes or models for synthetic drugs possessing physiological activities similar to the original. Examples: procaine and similar local anesthetics (cocaine)

4. natural products contain compound that demonstrate little or no activity which can be modified by chemical or biological methods to produce potent drugs.

Crude drugs vegetable or animal drugs that consist of

natural substances that have undergone only the processes of collection and drying

Classification:

Botanical Pharmaceutically

Pharmacological Pharmacologically

Chemical

Natural Substances refers to those substances found in nature

that comprises whole plants and anatomic parts thereof that have not had changes

fundamental changes in both public and scientists towards pharmacognosy.

1. use of classical plant drugs for the treatment of many ailments usually of the self-limiting variety

major pharmaceutical manufacturers

Derivatives or Extractives refers to single substance or

mixture of substances which are considered as the chief constituents obtained by the process of extraction.

Solvent or menstrum liquid or liquid mixture which removes only

those substances which dissolved by extraction

Marc the undissolved portion of the

drug that remains after extraction processis completed.

Geographic source and Habitat region in which the plant or animal

yielding the drug grows

Indigenous plants growing in their native

countries Naturalized

plants growing in s foreign land or in a locality other than their native homes.

. PREPARATION OD RUGS FOR THE COMMERCIAL MARKET:

1. Collection – collection of drugs from cultivated plants always ensures a true

natural source and a reliable product. The most advantageous

collection time is when the part of the plant that constitutes the drug is highest in its content of active principle and when the material will dry to give the maximum quality and appearance,

flower tops/leaves - when photosynthesis is active

flower - prior or just about the time of pollination

seed - collection when fully matured

gums and oleoresin- gathered during dry weather

fruits - collecting near the ripening period

made in their molecular structure as found in nature.

2. Harvesting - the mode of harvesting varies with each drug produced and with the pharmaceutic requirements of each drug. Medical devices : pickers, mowers, binders, swath, steel 3. Drying

Advantages: remove moisture prevent molding prevent action of bacteria fixes the constituents facilitate grinding and milling prevent environmental hydrolysis

types of drying: Air drying Artificial Air Drying *leaves and underground plant parts – screen trays, 40-60degreesC *drug cont’g volatile oil – air drying, temp 35degreesC * large & fleshly roots – slit or slice * bark, root, rhizome, seed and some fruit – not be raised over 35oC

4. Garbling – is the final stage in the preparation of crude drugs.

* consists of the removal of extraneous matter such as other parts of the plant, dirt and added adulterants and is carried out after the drug is dried and before it is baled of packaged.

5. Packaging, Storage and Preservation: * compressed bales *bags * paper boxes *sacks * barrels * cans * casks * matting foam

EVALUATION OF DRUGS: To evaluate means to identify and to determine the quality and purity of drugs

1. Organoleptic – refers to the evaluation of drugs by means of the organs of sense and includes the macroscopic appearance of the drug.

2. Microscopic- essential in the study of adulterant in powdered plants.

3. Biologic – pharmacological activity of certain drugs has been applied to their

evaluation and standardization

Organisms used for Biological evaluation of drugs:

bacteria microbiological method (

yeast/molds) – assaying of vitamins

living microscopic animals (Daphnia) – Digitalis

Gold fish – standardization Frogs – standardization Vitamins (rats/mice) – suffering

aviyaminosis Guinea pigs – test in toxicity and

antigenesity diphtheria Young adult domestic chicken-

standardizing ergot Pigeon – assaying digitalis Cat - assaying digitalis Rabbits – used in curare alkaloid Dogs – test for Veratrum

viride( antihypertension) Human – noting the drugs for

complete evaluation 4. Chemical- the active constituents of

many natural drugs have been determine

Chemical tests – conduct color reaction

Chemical assay – cellular and non-drug of plants origin that represent

active principle and purification of the chief principle *saponification number *iodine number *acid value of fixed oil

5. Physical – extensively applied to the active principle of drugs * solubility * specific gravity * optical rotation * congealing point * refractive index * melting point * water content

CLASSIFICATION OF DRUGS:

1. Morphology - refers to the classification of plants and animals

2. Taxonomy - refers to the natural relationship or phylogeny among plants and animals.

3. pharmacologic or therapeutic – refers to medicinal and their therapeutic effects

4. chemical constituent – activity and

therapeutic use of drugs base on chemicalconstituent.

CHEMISTRY OF NATURAL DRUG PRODUCTS

Constituents – chemical compounds found in plants and animals Active Constituents – compounds that are responsible for the therapeutic effect

1. pharmaceutically active- cause chemical changes in the medicinal preparation. Ex. Preparation containing tannic acid with iron cause pre-capitation.

2. pharmacologically active – responsible for the therapeutic activitywhich may either single chemical substances (sugars, starches,plantacids,enzymes, glycosides, steroids, alkaloids, proteins, hormones and vitaminsand mixtures chemical substances ( fixed oils, fats, waxes, volatile oils,resins, oleoresins, oelo-gum-resins and balsams.

Inert constituents – no definite pharmacologic activity (starch, coloring matter) Secondary plant substance –extracted , crystallized and purified where the presence of inert matter in active constituents which may modify or prevent absorbability or potency of the active constituents. 3 Principal factors that influenced the secondary constituents of drug plants 1. heredity (genetic composition) 2. ontogeny (stage of development) 3. environment (soil, Drug biosynthesis or biogenesis – study of the biochemical pathways leading to the formation of secondary constituents used as drugs .

CARBOHYDRATES AND RELATED COMPOUNDS

Carbohydrates - are aldehydes or ketone derivatives of polyhydric alcohols

containing Carbon, Hydrogen and Oxygen and are generally in the

same ratio as in H2O (2:1)

Classification|1. Sugars:

A. Monosaccharides- compounds that cannot be hydrolyzed to simple sugar - substances that is ketonic or aldehydic substitution product of a polydroxy alcohol 1. Trioses (C3H6O3) 2. Tetrose (C4H8O4) 3. Pentoses (C5H10O5)- xylose, ribose, arabinose, rhamnose -occur in nature usually as product of hydrolysis of hemicellulose, gums and mucilages 4. Hexoses (C6H12O6) – glucose, galactose, mannose, fructose - most important monosaccharides found in plants. - first detectable sugars synthesized by plants and firm monomer unita Of polysaccharides which include aldohexoses and ketohexosesB. Oligosaccharides – composed of

more than one saccharide group.1. disaccharide (C12H22O11)-

sucrose, lactose and maltose

2. trtisaccharide (C18H32O16) – raffinose

C. Pollysaccharides1. Homoglycans2. Heteroglycans

BIOSYNTHESIS OF CARBOHYDRATES;

Production of Monosaccharides By Photosynthesis. Produced by biologic process that converts electromagnetic energy into Chemical energy which consists of 2 classes of reactions 1. Light reaction that actually convert electromagnetic energy into chemical energy 2. Enzymatic reaction that utilizes the energy from the light reactions to fix carbon dioxide into sugar (dark reactions)

SUGAR AND SUGAR CONTAINING DRUGS

SUCROSE

Botanical Origin : Saccharum officinarum. Gramineae Beta vulgaris, Chenopodiaceae Acer saccharum, Aceraceae (sugar maple)

Synonyms : saccharum, sugar, cane sugar, beet sugar, table sugar Sources : sugar cane, sugar beets, sugar maple Use(s) : pharmaceutic necessity for syrup, demulcent, bacteriostatic preservative, mask disagreeable taste in troches and tablets :glucose and fructose are the products of hydrolysis DEXTROSE; (Blood Sugar) Synonyms : D-glucose, alpha-D (+) – glucopyranose Use : nutrient – may be given by mouth, by enema, by subcutaneous or IV injections, ingredient in dextrose, dextrose and NaCl inj. Source : grapes - obtained by controlled hydrolysis of starch. - product of hydrolysis of sucrose FRUCTOSE: Synonyms : D-fructose, levulose. B-D (-) fructopyranose, fruit sugar Sources : sweet fruits and honey Uses : food for diabetic person

- obtained by hydrolysis of inulin

- product of hydrolysis of sucrose in equal quantities with glucose

- ketone sugar that occurs naturally in most sweet fruit LACTOSE: Botanical Origin : Bos Taurus, Bovidae Synonym : Cows milk, milk sugar Use ; tablet diluent Source : fresh pasteurized or unpasteurized milk - glucose and galactose are products of hydrolysis

Processing of Milk (5% lactose) Butter – consist of united fat globules when churned

Buttermilk – this is the liquid that separates from butter Skimmed milk- milk left after separation of the cream Cheese- skimmed milk + rennin Whey – liquid separated from the coagulum containing lactose and inorganic salts XYLOSE : Pentose which is obtained by boiling corn cobs, straw or similar materials with dilute acid to hydrolyze the xylan polymer Synonym : D-Xylose. Wood Sugar Use : diagnostic agent since it is normally absorbed frpm the small Intestine , but it is not metabolized to a significant extent by ammalian enzyme.

DRUGS CONTAINING COMPOUNDS METABOLICALLY RELATED TO TO SUGARS

Products of Glycolytic and Oxidative Metabolism| CHERRY Botanical Origin : Prunus cerasus, Rosaceae Synonym : succus cerasi Active constituent: 1% malic acid Uses : preparation of cherry juice, flavored vehicle

ACIDS Plant acids such as citric acid, lactic and tartaric acids find wide application in the formulation of foods and medicines as acidulant or components of buffer system to control acidity.

- less irritation. - non-toxic

Citric Acid ( 2-hydroxy 1,2,3, propane trioic acid)

- 1st isolated in crystal form from lemon juice by Scheele in 1784

- Present in many fruits and plants

- Obtained commercially from lemons, limes or pineapple

but mostly by fermentation of sucrose- use in buffering

system, acidulant in effervescent formulations

Lactic Acid ( alpha-hydroxy propionic acid)

- acidulant in infant feeding formulas

- Na lactate injection is an electrolyte replenisher for treatmentmetabolic acidosis.

Tartaric Acid ( 1,2,3, dihydroxy butane dioic acid )

- dicarboxylic acid obtained as a by product of the wine industry

- substitute for citric acid in buffer system and in effervescent

formulation

Alcohol or Ehtanol Products through Distillation process (40-55% alcohol)

brandy – distilled wine whiskey – distillation

product from fermented malted grain

rum - fermented product from molasses

wine used as a mild stimulant and tonic

brandy and whiskey are classed as CNS depressant

Products of Reductive Metabolism Dulcitol, mannitol, sorbitol and other sugar alcohols are widely distributed in plants. Mannitol

- D-mannitol is a hexahydric alcohol obtained by reduction of mannose or by isolation from Manna (dried saccharine exudateof Fraxinus ornus, Oleaceae containing 50 to 60% of mannitol

- Use pharmacologically as osmotic diuretic

- Used as diagnostic aid and as an osmotic diuretic because when

administered prarenterally, it is not metabolized and is eliminated readily by glomerular filtration

- usual diagnostic dose of mannitol injection 200mg/kg. body wt in a

15-25% solution IV in 3-5 minutes - usual diuretic dose is 50-100 g daily dose in a 5-25% solution by

Sorbitol IV infusion- Sorbitol of D-glucitol

is a hexitol obtained from the ripe berries of mountain ash, Sorbus aucuparia, Rosaceae

- well known hexahydric sugar alcohol

- taste approximately half as sweet as sucrose

- has humectant properties

- useful ingredient in toothpaste, chewing gums and various dietetic products

POLYSACCHARIDE and POLYSACCHARIDE CONTAINING DRUGS Polysaccharide are polymers of monosaccharides (sugar) linked together through glycosidic(ether) linkages.

- systematic nomenclature are given the ending “an:

- glycan is another word.

- Homoglycan- polysaccharide if one type of monosaccharide unit

is present- Heteroglycans -

polysaccharide if more than one kind of

monosaccharide is present.

HOMOGLYCANS HETEROGLYCANS Starch Gums Plantago Seed Hetastarch Tragacanth Guar Gum

Inulin Acacia Locust Bean Gum Cellulose Karaya Gum Xanthan Gum Purified Cotton Sodium Alginate Powdered Cellulose Agar Carrageenan

STARCH Botanical Origin : Zea mays, Graminae (matured grain of corn) Triticum aestivum (wheat) Solanum tuberosum , Solaneceae (potato tubers) Chemistry and Properties of Startch 1. amylose – linear molecule composed of 250 to 300 D-g;ucopyranose units uniformly linked by alpha 1,4 glucosidic bonds

- soluble in water - contain 25% in starch- deep blue complex

when react with iodine

2.amylopectin – consist of 1000 or more glucose units that are also connected

with alpha1,4 linkages

- branched component of starch

- 75-80% contain in starch

- blue-violet or purple color when react with iodine

- paste forming properties of starch

Uses - used as an ingredient in dusting powder

- tablet binder and disintegrant

- antidote for iodine poisoning

glutens- tachy proteins removed from corn and wheat in the preparation of starch

Pregelatinized starch – starch that has been chemically or mechanically processed to to rupture all part of the granules in the presence of water.

Sodium Starch glycolate- semisynthetic material, is the sodium salt of a carboxymethyl

ether of starch.- used as a

disintegration agent in tablet formulation,

Hetastarch – semisynthetic material that is prepared in such a manner that it is approximately 90% amylopectin

- 6% solution is used as plasma expander

- adjunct therapy in the treatment of shock caused by hemorrhage,burns, surgery, sepsis or other trauma.

Inulin or hydrous inulin is a D-fructo-furanose polymer

- obtained from the subterranean organs of members of family Compositae

Dextran Botanical Origin : Leuconostoc mesenteroides

- 1,6-linked polyglucan- Formed from sucrose

by the action of a transglucosylase enzyme

( dextran sucrase) CELLULOSE

- most abundant organic compound on earth

- chief polysaccharide of plant cell walls.

Purified Cotton is the hair of the seed of cultivated varieties of Gossypium Hirsutum, Malvaceae ( Arabic gos, meaning silky substance and rough or hairy)

- also referred to as absorbent cotton

- employed as a surgical dressing,

HETEROGLYCANS Gums – are natural plant hydrocolloids that may be classified as anionic or nonionic polysaccharides or salt of polysaccharides .

- translucent, amorphous substances that are produced frequently in higher plants as a protective after injury

- Sources of commercially useful gums1. shrub/tree exudates

acacia karaya tragacanth ghatti 2. Marine gum agar algin carrageenan 3. Seed gum guar locust gum psyllium

4. Microbial dextran xanthan

5. Starch and Cellulose drivatives hetastarch methylcellulose TRAGACANTH (tragos (goat), akantha(horn) Botanical Origin : Astragalus gummifer, Leguminosae(dried gummy exudate astraglus means milkbone which refer to the exuding and subsequent hardening of the drug gumifer means gum bearing AC : 60-70% bassorin, a complex of polymethoxylated acids which swells in water but does not dissolve : 30% tragacanthin , a demethoxylated bassorin and is more water-soluble component Uses : suspending agent for insoluble powdered in mixtures emulsifying agent for oils and resin as an adhesive demulcent and emollient in cosmetic(hand lotion)

ACACIA ( akakia(pointed or thorny) Botnical Origin : Acacia senegal, Leguminosae) Senegal (habitat) Synonym : gum Arabic AC : arabin, complex

mixture of Ca, Mg,and K salts of arabic acid (branched polysaccharide that yields L-arabinose,D-galactose,D-glucoronic acidand L-rhamnose on hydrolysis below 60% of alcohol is useful in drug formulation Uses ; suspending agent. demulcent and emollient adhesive and binder in tablet granulation GHATTI GUM

Botanical Origin : Anogeissus latifolia, Combretaceae Synonym : Indian gum

-used as a substitute for acacia

KARAYA GUM Botanical Origin : Sterculia urens, S. villosa, S. tragacantha, Sterculiaceae Synonym : Sterculia gum A.C. : D-galacturonic acid and D-glucoronic acid Uses : bulk laxative, as an agent for forming emulsions and suspension and dental adhesive SODIUM ALGINATE (brown seaweeds)

Botanical Origin : Macrocystis pyrifera, Lessoniaceae Synonym : Algin or alginic acid- the principal constituent of the cell Walls of the brown algae. AC : Na salt of alginic acid, a linear polymer of L-guluronic acid and D-mannuronic acid (major component) Uses : suspending agent, tablet binder, thickening agent

AGAR (red algae) Botanical Origin : Gelidium cartilagineum, Gelidiaceae Synonym : Japanese Isinglas AC : agarose/agaropectin Uses : laxative, s.a., e.a.,tablet excipient and disintegrant,

CARRAGEENAN (red algae or seaweeds) Botanical Origin : Chondrus crispus,

Gigantinaceae Gigartina mamillosa, Gigantinaceae Synonym : chondrus, Irish moss AC : k-carageenan, i-carageenan (good gelating agent / carageenan (nongelling n useful thickener) Uses : demulcent, bulk laxative

DANISH AGAR (red algae) Botanical Origin : Furcellaria fastigiata, Synonym : furcellaran AC : k-carrageenan Use : suspensind agent

PLANTAGO SEED

Botanical origin : Plantago psyllium, P. indica, P. ovata, Plantaginaceae Synonym : psyllium seed, plantain seed Use : cathartic

GUAR GUM (seed)

Botanical origin : Cymopsis tetragonolobus, Fabaceae Synonym : guaran AC : 1,4 linked D-mannopyranosyl Use : laxative, thickening agent, binder

LOCUST BEAN GUM (seed)

Botanical Origin : Ceratonia siliqua, Fabaceae Synonym : carob pulp, St. John’s bread Use : used as chocolate substitute

XANTHAN GUM (microbial gim) Botanical origin : Xanthomonas campestris AC : branched partially acetylated polysaccharide containing D-glucose, D-glucoronic acid and D-mannose Use : excellent s.a. and e.a. :The pseudoplastic property enable tootpaste and ointment

both to hold their shape and to spread readily.

PECTIN - Group of polysaccharide present in the primary cell walls of all seed- bearing plants and are located particularly in the middle lamellae of cell walls and are abundant in fruits (apples & oranges) and roots (beets and gentian) -purified carbohydrate product obtained from the dilute acid extract of inner portion of the rind of citrus fruits from or from apple pomace.

AC - linear 1,4 linked D-galacturonan Uses - protectant, s.a., ingredient in many antidiarrheal formulation

PHILIPPINE SOURCES OF CARBOHYDRATES

A, UNDERGROUND PARTS Tikas, Canna indica, Cannaceae Gabi, Colocasia esculenta, Araceae Ubi, Dioscorea alata, Dioccoreacae Tugi, Dioscorea esculenta, Dioscoreaceae Kamote, Ipomoea batatas, Convolvulaceae Kamoteng kahoy, Manihot exculenta, Euphorbiaceae Araro, Maranta arundinacea, Marantaceae Patatas, Solanum tuberosum, Solanaceae

B. STEM

Aroma, Acacia farnesiana, Leguminosae Jute, Corchorus capsularis, Tiliaceae Tubo, Saccharum officinarum, Gramineae

C. TOP

Saluyot, Corchorus officinarum, Gramineae

D. FRUIT Rice, Oryza sativa, Gramineae Cor, Zea mays, Gramineae

E, SEED HAIR Kapok, Ceiba pentandra, Bombaceae

Malabulak, Gossampinus heptaphylla, Bombaceae Bulak kastila, Gossypium brasiliense, Malvaceae Bulak, Gossypium hirsutum, Malvaceae

F. ENTIRE PLANT Eucheuma, Eucheuma spp., Solieriaceae Gulaman, Gracilaria spp., Sphaerococcaceae

Tests for Carbohydrates:

1. Reduction of Fehling’s solutions ( copper sulfate, NaOH & Rochelle salt)

- brick red precipitate of cuprous oxide

- reducing sugars include all monosaccharides, many dissacharides( lactose, maltose, cellobiose and gentiobiose)

- non-reducing sugar includes some saccharides (sucrose) 2. Molisch’s test -general test for carbohydrates - give a purple color when treated with alpha naphthol and conc, Sulfuric acid.

3.Osazone formation- formed by heating s sugar solution with phenylhydrazine hydrochloride, sodium acetate and acetic acid.

-form a yellow insoluble compounds of varying structures called osazones -serves to identify the different sugars

4. Test for pentoses- an equal volume of HCl acid containinga little phloroglucinol - formation of red color 5. Resorcinol test for ketones or also known as Selivanoff’s test - resorcinol and conc. HCl - red color is formed 6. Keller-Killiani test for deoxysugars ( cardiac glycosides) - sugar is dissolve in acetic acid containing a trace of FeCl3 and H2SO4 . - reddish brown color

is produced at the junctions of the liquid