Pharmacognosy - General Introduction & History (PDF)

GENERAL INTRODUCTION Definition of Pharmacognosy Pharmacognosy is study drugs derived from natural sources. The natural sources of drugs include: plants, animals, microorganisms and mineral sources. The word "pharmacognosy" is derived from the Greek words pharmakon (drug), and gnosis which means "k...

GENERAL INTRODUCTION Definition of Pharmacognosy Pharmacognosy is study drugs derived from natural sources. The natural sources of drugs include: plants, animals, microorganisms and mineral sources. The word "pharmacognosy" is derived from the Greek words pharmakon (drug), and gnosis which means "knowledge" or gignosco which means to acquire knowledge of. Pharmacognosy is the study of medicines derived from natural sources. Like many contemporary fields of science, Pharmacognosy has undergone significant change in recent years and today, it represents a highly interdisciplinary science which is one of the major areas of pharmaceutical education. Pharmacognosy is defined more precisely according to the American Society of Pharmacognosy (ASP) as the study of the physical, chemical, biochemical and biological properties of drugs, drug substances, or potential drugs or drug substances of natural origin as well as the search for new drugs from natural sources. Pharmacognosy has played a pivotal role in the discovery and development of new drugs and therapies, and has been continuing to do so even today. It also formed the basis of the development of the subject “Pharmacy.” History of the Development of Pharmacognosy The history of Pharmacognosy is as old as the history of medicine. The Papyrus Ebers is an old document written in 1500 B.C which described the use of medicinal plants, animal and human anatomy by the ancient Egyptians. The Greek physician Hippocrates: father of medicine (460-370 B.C) described human anatomy and physiology. Hippocrates, the founder of Greek medicine and Aristotle, the pupil of Hippocrates, used medicinal plants for the treatment of diseases. Aristotle, a renowned philosopher and a student of Pluto (384-287 B.C) is known for his studies of Animal Kingdom. Theoprastus a Greek scientist (370-287 B.C), who is a student of Aristotle is well known for the study of plant kingdom. He founded the School of Medicinal Plants Dioscorides (A.D. 78), Greek physician described many medicinal plants and their properties in an Encyclopedia, called De Materia Medica. He described 600 therapeutic medicinal plants in the form of a series of scientific studies on medicinal plants. Pliny the Elder (A.D. 23-79) compiled the Natural history (Historia Naturalis) in 37 volumes. The Natural History is an astonishingly ambitious work that ranges from astronomy, art, magic, geography and zoology. It is an unrivaled compendium of Roman knowledge. The great Greek pharmacist Galen (A.D. 131- 200) described various methods of preparation containing active constituents from plant and animal sources and it is known as galenical pharmacy. Later on all the detailed information’s were compiled to form Materia Medica that was that was utilised by physicians. The term pharmacognosy was used for the first time by the Austrian physician Johann Adam Schmidt in 1811. The word appeared in his handwritten manuscript Lehbuch der Materia Medica. Sydler, a German scientist introduced the term Pharmacognosy in 1815 in his work “Analecta pharmacognostica”. Originally during the 19th century and the beginning of the 20th century "pharmacognosy" was used to define the branch of medicine or commodity sciences (Warenkunde in German) which deals with drugs in their crude, or unprepared form. Crude drugs are the dried, unprepared material of plant, animal or mineral origin, used for medicine. The study of these materials under the name pharmakognosie was first developed in German-speaking areas of Europe, while other language areas often used the older term Materia medica taken from the works of Galen and Dioscorides. In German the term drogenkunde ("science of crude drugs") is also used synonymously. Relationship of Pharmacognosy with other subjects Pharmacognosy is interdisciplinary, drawing on a broad spectrum of biological and socio-scientific subjects, including botany, ethnobotany, medical anthropology, marine biology, microbiology, herbal medicine, chemistry, biotechnology, phytochemistry, pharmacology, pharmaceutics, clinical pharmacy and pharmacy practice. The contemporary study of pharmacognosy can be divided into several fields with few mentioned below: Medical ethnobotany: the study of the traditional use of plants for medicinal purposes. Ethnopharmacology: the study of the pharmacological qualities of traditional medicinal substances. Phytotherapy: the medicinal use of plant extracts. Phytochemistry: the study of chemicals derived from plants (including the identification of new drug candidates derived from plant sources. Zoopharmacognosy: the process by which animals self-medicate, by selecting and using plants, soils, and insects to treat and prevent disease. Pharmcognosy-Biotechnology: the synthesis of natural bioactive molecules using biotechnology. Herbal interactions: the interactions of herbs with other drugs and the body. Marine Pharmacognosy: the study of chemicals derived from marine organisms. Marine Pharmacognosy Marine pharmacognosy is the investigation and identification of medically important plants and animals in the marine environment. Generally the drugs are obtained from the marine species of bacteria, virus, algae, fungi and sponges. Many antimicrobial, antiviral, antiparasitic, anticancer drugs have been obtained from these marine organisms. The oceans and the seas covers about 70% of earth’s surface and possess nearly several deserted species of plants and animals from marine sources and some of them are exclusively of the marine ecosystem. Significance of Marine Sources Marine flora and fauna play significant role as a source of new molecular entity. The oceans of the world contain over 5 millions species in about 30 phyla. The Marine natural products consists of a wide variety of chemical classes including: Terpenes, Shikimates, Polyketides , Acetogenins, Peptides and Alkaloids The Development of Marine Drugs In Modern Times It has been known for centuries that sponges contain bioactive compounds that are of potential medical importance. Richter in 1907 outlined that the active component of the roasted bath sponge, used already by Roger against struma, is iodine. In the 19th and early 20th centuries, cod liver oil was in use as supplementary nourishment. However, only in middle of 20th century scientists began to systematically probe oceans for medicines. By the early 1950’s, Ross Nigrelli of the asborn laboratories of the New York aquarium, extracted a toxin from auvierian organs of the Bahamian Sea Cucumber, Actynopyga agassizi. He named this toxin as ‘Holothurin’ which showed some antitumor activity in mice. During the last 30-40 years numerous novel compounds have been isolated from marine organism having biological activities. Researchers found that marine organisms have defensive chemical weapons (secondary metabolites) for their protection. These compounds help them to deter predators, keep competitors at bay or paralyze their prey. Investigations in their chemical ecology have revealed that the secondary metabolites not only play various roles in the metabolites of the producer but also in their strategies in the given environment. Methods of Collection of Marine Drugs 1) Beach Combing 2. Wading 3. Snorkeling 4. Dredging 5. Corers 6. Scuba Diving 7. Submersibles Methods of Drying Drying should be done before extraction by lyophilization (Freeze drying) or can be dried at certain temperatures to remove any excess water and debris. Isolation Techniques Extraction (Methanol, Chloroform, Ethanol, Acetonitrile, etc., Chromatographic Purification De replication (LC-MS, NMR) Structure elucidation (HR-MS, TMS, NMR, IR, UV-Vis, etc.,) Bio-assay testing (anticancer, antimicrobial, antiviral, anti-inflammatory, antiparasitic, anticholesterolemic, etc., The Scope of Pharmacognosy The scope of the subject pharmacognosy include studies/researches in the areas of: Phytochemistry Microbial chemistry Biosynthesis, Biotransformation, Chemotaxonomy, Biotechnology, Other biological and chemical sciences. Note: Although most pharmacognostic studies focus on plants and medicines derived from plants, other types of organisms are also regarded as pharmacognostically interesting, in particular, various types of microbes (bacteria, fungi, etc.), and, recently, various marine organisms. Pharmacognosy is one of the major divisions of the pharmaceutical curriculum, represents the oldest branch of the profession of pharmacy. In a restricted sense, the definition of pharmacognosy implies a particular knowledge of methods of identification and evaluation of drugs. In a broad sense, pharmacognosy embraces knowledge of the history, distribution, cultivation, collection, selection, preparation, commerce, identification, evaluation, preservation, and use of drugs and economic substances affecting the health of man and other animals. Function of Pharmacognosist: 1. Identification of the drug sources 2. Determination of the morphological character 3. Investigation of potency, purity, and admixture 4. Planning and designing of the cultivation of medicinal plants 5. Prescription of the detail processes of collection, drying and preservation 6. Knowledge about active constituents, chemical nature and uses of the active constituent. SOME BASIC TERMINOLOGIES USE IN PHARMACOGNOSY Drug: This is anything that is used in modifying conditions of animals and human in disease conditions. Drugs can be from natural, semi synthetic and synthetic origin. In real sense drugs can be referred to as true drugs or crude drugs. Crude Drugs: These are drugs that are derived from natural forms; from plants, animals and minerals. Crude drugs can be divided into organized and unorganised drug. Most crude drugs are derived from plant origin and are thus referred to as vegetable drugs. A crude is a drug that has undergone only collection and drying. It physical and chemical properties have not been enhanced by any method. Organised (cellular) drugs: these are crude drugs that characteristically contained cellular structures. Examples includes Digitalis, Cinchona, clove, jalap, cochineal etc. Unorganised (acellular) drugs: These are crude drugs that do not contain cellular structures. Examples includes Aloe, Agar, colophony, bees-wax, castor oil, opium etc. Vegetable drugs: these are crude drugs derived from plants. Plants are the most important source of drugs and must research and a study of crude drugs is on vegetable drugs. Non-vegetable drugs: these are drugs derived from sources other than plants and can be referred to as animal derived if they are from animal sources or mineral derived if they are from mineral sources Taxonomic(Biological) classification This is the botanical/zoological classification of drugs. It is the phylogenic classification according to their division, class, order, family, genus and species. This system gives the details and idea about the source. The crude plant drugs are classified based on accepted botanical classification, while animal derived drugs are classified based on established zoological classification. A large number of plant species have distinguishing characteristics that permit crude drugs from families to be studied, in most cases only part of the plant source is used as drugs. In most cases the whole plant source is rarely used as drugs. Example include Cascara bark, Nux-vomica seeds, Digitalis leaves, Quassia wood, pyrethrum flower etc. in case of animals, all terrestrial and marine animals are grouped according to their phylogenic relationships. Example of some few crude drugs classification base on this system. (I) (II) Phyllum…………Spermatophyta Phyllum…………Spermatophyta Division…………Angiospermae Division…………Angiospermae Class…………….Dicotyledons Class…………….Dicotyledons Order……………Rosales Sub-class……….. Sympetalae Family……..……Leguminosae Order……………Tubiflorae Subfamily…….…Papilionaceae Family……..……Solanaceae Genus…..………Glycerrhiza, Astragalus, Indigofera Subfamily…….…Papilionaceae Species………….. glabra, gummifer, tictoria Genus…..………Atropa, Hyoscyamus, Datura Species………….. belladonna, niger, stramonium Morphological Classification The crude drugs are grouped according to the part of the plant or animal into organised or un-organised drugs. The organised vegetable drugs are for example classified into leaves, flowers, seeds, woods, barks, and subterranean parts like roots and rhizomes. The un-organised vegetable drugs are classified into drugs like latex, gums, extracts, etc. Examples of drugs under this classification Seeds: Nux-vomica, Strophanthus, castor Leaves: Digitalis, Senna, Eucalyptus Barks: Cascara, Cinchona, Cinnamon Woods: Quassia, Sassafras, Sandalwood Roots: Rauwolfia, Ipecacuanha, Aconite, Jalap Rhizomes: Turmeric, Ginger, Podophyllum Flowers: Clove, Pyrethrum, Saffron Fruits: Fennel, Coriander, Colocynth Entire Drugs: Ephedra, Ergot, Cantharides, Belladona Dried Latices: Opium, Gutta-percha, Papain Resin and Resin combination: Balsam of tolu, Myrrh, Asafoetida, Benzoin Dried Juices: Aloes, Kino, Red Gum Gums: tragacanth, Acacia, Guar Dried Extract: Gelatin, Catechu, Agar This system of classification is more convenient for practical study especially when the chemical nature of the drug is not clearly understood. Chemical Classification The crude drugs are classified according to the chemical nature of their most important constituent. Since the pharmacological activity and therapeutic significance of crude drugs are based on the nature of their chemical constituents, it would appear that chemical classification of crude drugs is preferred. The crude drugs containing alkaloids are grouped together regardless of their morphology and taxonomic relationship. Examples of Chemical classification Glycosides: Digitalis, senna, cascara, liquorice Alkaloids: Nux-vomica, Ergot, Cinchona, Datura Volatile oils: peppermint, clove, eucalyptus, garlic Lipids: Castor oil, Bees-wax, Lanolin, Cod-liver oil, cocoa-butter Carbohydrates and derived products: Acacia, agar, Guar, pectin, honey, ispangula Resin and Resin combinations: Colophony, Jalap, Balsam of Tolu, Vitamins and Hormones: Yeast, Shark liver oil, oxytocin, insulin Proteins and enzymes: Casein, Gelatin, papain, trypsin Pharmacological (therapeutic) classification This system of classification involves the grouping of crude drugs according to the pharmacological action of their chief active constituent or their therapeutic uses. Regardless of morphology, taxonomy, or chemical relationship, the drugs are grouped together, provided they exhibit similar pharmacological action. Thus cascara, castor oil and senna are classified as laxatives or purgatives because of their common pharmacological action. Similarly, Gentian, Cinchona, Nux-vomica and Swertia are grouped as bitters. Drugs differing in mechanism of action but with the same pharmacological effect are grouped together; e.g bulk- purgative, irritant laxative and emollient purgative are classified together. Some examples of Pharmacological classification of drugs Drugs acting on gastro-intestinal tract Bitters: Gentian, Quassia, Cinchona Carminatives: Dill, Mentha, cardamom Emetics: Ipecacuanha Purgatives: Senna, Castor oil Drugs acting on cardio-vascular system Cardiotonics: Digitalis, squill, Strophanthus Cardiac depressants: Cinchona, Veratrum Vaso-constrictors: Ergot, Ephedra Antihypertensives: Rauwolfia Drugs acting on the autonomic nervous system Adrenergics: Ephedra Cholinergics: Physostigma, Pilocarpus Anticholinergics: Belladona, Datura Anti-cancer Vinca, Podophyllum, Taxus, Camptotheca Chemotaxonomic identification The recent advances in the knowledge of phytochemistry have revealed the existence of relationship between chemical constituents and taxonomic status. Chemotaxonomy establishes a relationship between the plant and the chemical facts for understanding the biological evolution and relationship. Plants are classified based on certain chemotaxonomic markers, especially as it relates to those that have pharmaceutical importance. The characters studied in chemotaxonomy are secondary metabolites; this knowledge can serve as a basis for classification of drugs. Usually the plants are classified based on the distribution of chemotaxonomic markers. Recently techniques of DNA hybridisation, amino acid sequencing in proteins and serotaxonomy could serve as tools in crude drugs identification and classification. Adulteration and Evaluation of drugs Adulteration of crude drugs Adulteration is act of incorporation of impurities in genuine or standard drugs; this may be accidental or deliberate. In few cases dealers mix the substandard and spoiled drug with genuine ones due to scarcity or high price of the commodity. Adulteration may occur due to improper collection, drying, preparation, and storage of crude drugs. In this way the crude drugs are of inferior quality containing fewer amounts of bioactive compounds and more of foreign matter. There are various methods in which drugs are adulterated. Evaluation of crude drugs Evaluation is the determination of Identity, quality and purity of drugs. Important terminologies in evaluation of crude drugs include: Identity: This refers to exact biological source of drugs. Quality: It refers to the quantity or concentration of biologically active constituents present in the crude drugs. Purity: It refers to the absence of both organic and inorganic foreign matter. There are different methods for evaluation of crude drugs. These include: Organoleptic evaluation, microscopic evaluation, physical evaluation, chemical evaluation and biological evaluation. Secondary metabolites They are secondary plant constituents or chemicals (compounds) produced by plants as waste products (or by-products) during their normal metabolic activities. The secondary metabolites are of no primary importance to the plant. Their absence may not cause any impairment to the plant. They are also produced plants when there is change of environmental conditions e.g., microbial attack (fungi, virus or bacteria) or attack by herbivores. Here the chemicals are produced as defence mechanism. Examples of Secondary Metabolites These include: Flavonoids, Alkaloids, Terpenoids, Steroids, Tannins, Saponins, Glycosides, Anthraquinones, etc. Importance of Secondary Metabolites (Natural products) Compounds from natural sources play four significant roles in modern medicine: 1. Bioactive compounds for direct use as drug, e.g. digoxin. 2. They provide a number of extremely useful drugs that are difficult, if not impossible, to produce commercially by synthetic means 3. Natural sources also supply basic compounds that may be modified slightly to render them more effective or less toxic 4. Their utility as prototypes or models for synthetic drugs possessing physiologic activities similar to the originals 5. Some natural products contain compounds that demonstrate little or no activity themselves but which can be modified by chemical or biological methods to produce potent drugs not easily obtained by other methods e.g., Baccatin III converted to Taxol (anticancer drug). ANTHRACENE (ANTHRAQUINONE) GLYCOSIDES Anthracene glycosides are mainly found in dicotyledonous plants but to some extent it is also found in monocotyledonous and lower plants. The anthracene glycoside are characterized by the laxative action they produce on humans and other animals. Their basic structure is based on anthracene: Anthracene It consists of glycosides formed from aglycone moieties like anthraquinones, anthranols, anthrones or dimers of anthrones or their derivatives. Anthraquinone (Aglycone) Frangulin A (An example of Anthracene glycoside) Note: A glycoside is a molecule consisting of two parts (or moieties): (i) Glycone (sugar) and (ii) Aglycone (non-sugar or genin). Glycone moiety: The sugars present are usually arabinose, rhamnose and glucose. Glycone moiety: The sugars present are usually arabinose, rhamnose and glucose. Properties of Anthraquinones Anthraquinone is an aromatic organic compound and a derivative of anthracene. It has the appearance of yellow or light gray-green solid crystalline powder. Its chemical formula is C14H8O2. It melts at 286 oC, boils at 379.8 oC. It is insoluble in water or alcohol but dissolves in nitrobenzene and aniline. It is chemically fairly stable under normal conditions. Main Medicinal use of anthraquinones The natural anthraquinones and related glycosides are stimulant cathartic (laxative laxatives) and exert their action increasing the tone of the smooth muscle in the wall of large intestine. A research on rhein glycosides (anthraquinone glycoside) shows that this compound increases pressure on the walls of the colon (They are irritant and stimulate peristaltic movement), thus pushing the stools outside. Sources of Anthraquinones Anthraquinone naturally occurs in some plants (e.g., aloe, senna, rhubarb and cascara), fungi, lichens, and insects, where it serves as a basic skeleton for their pigments. Anthracene glycosides These glycosides are characterized by a chemical test, known as Borntrager’s test and show the property of *microsublimation. Most of the glycosides are O-glycosides and S-glycosides, by their hydrolysis derivatives of 1:8 dihydroxy anthraquinone, anthranol, anthrone, or dianthrone are obtained. Aglycone moiety: The common aglycones are aloemodin, emodin, rhein, chrysophanol and physcion which may exist as anthraquinones, anthranols or anthrones. Glycone moiety: The sugars are usually arabinose, rhamnose and glucose. In the drug originally, the glycosides of reduced derivatives or their dimers are present. During drying and storage; hydrolysis and oxidation occur and free anthraquinones are produced. Chemical Assays: All anthracene compounds are oxidized to free anthraquinones by ferric chloride. Furthermore, they are treated with NaOH and are made into red alkali salts which are estimated using spectrophotometer at 510-540 nm, using 1:8 dihydroxyanthraquinone as standard. Bioassay: Bioassay is carried out on mice or rats by counting the number of wet faeces after administration of the drug according to the weight of animals for determing thepurgative activity of the anthracene. Note: Microsublimation: Is the sublimation of a minute quantity of a material for microscopic examination. Oxanthrone Anthraquinone Anthrone Anthranol Dianthrone Structure of Anthraquinone and Anthraquinone derivatives Test for anthraquinones (Borntrager’s reaction for free anthraquinones). One gram (1 g) of the powdered sample was placed in a dry test tube and 20 mL of chloroform was added. This was heated in steam bath for 5 min. The extract was filtered while hot and allowed to cool. To the filtrate was added with an equal volume of 10% ammonia solution. This was shaken and the upper aqueous layer was observed for bright pink colouration as indicative of the presence of Anthraquinones. Control test were done by adding 10 mL of 10 % ammonia solution in 5ml chloroform in a test tube. CASCARA SAGRADA Synonyms: Cascara Bark, Sacred Bark, Chittem Bark Botanical source: Cascara Sagrada consists of the dried bark of Rhamnus purshiana D.C., collected at least one year before being used. The plant is a shrub or small tree belonging to the family Rhamnaceae. Geographical source: The plant is cultivated in Britain, Columbia, Oregon, California and Kenya. Macroscopical characters: The bark occurs in single quills or channelled or flat pieces, 5-20 cm in length, up to 2 cm in width and 1-4 mm in almost smooth cork with pale brown, transversely elongated lenticels, occasional patches of silver- grey lichens and mussel-scale insects. Inner surface has longitudinal striations and faint transverse corrugations. Fracture is short and granular to the outer side but somewhat fibrous to the inside. Odour is faint but characteristic; it has bitter taste and it is nauseous. Microscopical characters: The cork consists of several rows of small, flattened, polygonal cells with reddish-brown contents. The outer cells of the cortex are collenchymatous and the inner ones rounded, which contain minute starch grains. Numerous idioblasts contain rosettes calcium oxalate. Stone cells occur in oval or rounded, yellow-coloured groups and are thick-walled, striated and pitted. Slender phloem fibres occur in narrow, elongated tangential groups and are associated with sheaths of idioblasts containing prisms of calcium oxalate. Sieve tubes occur in groups and are not accompanied by companion cells. Chemical constituents: Cascara sagrada contains 1.5-2 % of emodine and other similar anthraquinone glycosides. It also contains dextrose and an enzyme. Uses: Cascara Sagrada is a cathartic drug, mainly used for the correction of habitual constipation. Substitutes and adulterants: The dried bark of Rhamnus frangula Linn. is the common substitute. Barks of other species of Rhamnus are used adulterants. Chemical tests: It gives red colour with 5% KOH solution. SENNA LEAVES Synonyms: Alexandrian Senna, Nubian Senna, Cassia senna Biological source: Alexandrian senna consists of dried leaflets of Cassia acutifolia Dell of the family Leguminosae (Fabaceae). Geographical source: Egypt, Nubia, Arabia, Sennar Chemical constituents: Senna contains sennosides A and B which is based on sennidin A and B, Sennosides C and D which are glycosides of heterodianthrones of aloe-emodin and rhein. Uses: The medicinal action of Senna can be attributed to the anthraquinone glycosides; especially sennoside A and B. It appears that the aglycone portion is responsible for its pharmacological action. The main pharmacological active of anthraquinone glycosides in the laxative action. Chemical Test: Borntrager’s test The leaves are boiled with dilute sulphuric acid and filtered. To the filtrate, organic solvents like benzene, diethyl ether, or chloroform is added and shaken. The organic layer is separated and to it add ammonia solution, the ammoniacal layer produces pink to red colour indicating the presence of anthraquinone glycoside. RHUBARB Synonyms: China Rhubarb, Turkey Rhubarb, Indian Rhubarb Botanical source: Rhubarb consists of the peeled dried rhizomes and roots of Rheum palmatun Linn. Of the family Polygonaceae Geographical source: Tibet, China Chemical constituents: Rhubarb contains free anthraquinones, their glycosides, reduced derivatives, anthrones, or dianthrone and heterodianthrones. The anthraquinones of rhubarb are chrysophanol, oloemodin, emodin, phycion and rhein. Chemical test: Bontrager’s test: When Rhubarb powder is treated with ammonia, pink colour is produced. KOH Test When treated with 5% solution of KOH, it gives blood read colour. Uses The root is anticholesterolemic, antiseptic, antispasmodic, antitumor, aperient, astringent, cholagogue, demulcent, diuretic, laxative purgative stomachic and tonic. FRANGULA BARK Synonyms: Black Dogwood, Buckthorn Alder Biological source: It is the dried bark of Rhamnus frangula Linn. of the family Rhamnaceae Geographical source: Europe, Northern Asia, England and Scotland Chemical constituents: The bark contains glucofrangulin (frangula-emodin-6-rhomnose 8-glucoside), resins, resinous bitter substance and tannic acid Uses: The bark is used as purgative. The fresh bark acts as an irritant poison on the GIT. ALOES Biological source: Aloe is the dried juice collected by incision, from the bases of the leaves of various species of Aloe which include: Aloe perryi Baker, Aloe vera Linn. Or Aloe barbadensis Mil. and Aloe ferox Miller of the family liliaceae. Geographical source: Zanzibar islands, Barbados island Chemical constituents: The important chemical constituents include: Aloin, Aloesin, Barboloin and Isobarboloin Chemical tests: Borntrager’s test Uses It used as purgative, vermifuge. The plant is used as emmenagogue, emollient, stimulant, stomachic, tonic and vulnerary.  COUMARINS GLYCOSIDES Introduction Coumarins are phenolic compounds widely distributed in the plant kingdom. In these type of glycosides, the aglycone is coumarin. Naturally occurring coumarins have been isolated from numerous plants, particularly members of the Apiaceae (Umbelliferae) Rutaceae, and Fucaceae, Rubiaceae (Galium odoratum-woodruff), Poaceae (Hierochloe odorata-Sweet grass), as well as from some genera of Leguminosae (Fabaceae)- (Dipteryx odorata Tonka beans). Characteristics of Coumarins They are derivatives of benzo α-pyrone and have aromatic smell (like vanilla) and their alcoholic solutions when made alkaline produces blue or green fluorescence. The naturally occurring coumarins are classified base on the benzo 2-pyrone nucleus. α-Pyrone Benzo 2-pyrone (coumarin) or benzo α-pyrone Formation of Coumarin Nucleus This basic nucleus for the formation of coumarin is considered to be derived from o-hydroxy cinnamic acid (or o-coumarin acid) by its dehydration to yield the fused lactone ring. -H2O/lactonization Dehydration o-hydroxy cinnamic acid Coumarin (a lactone) Types of Coumarins  Coumarins Coumarin can occur in free state or combined state with sugar (i.e., as glycosides). The common example of sugar present in coumarins is glucose. Examples of free coumarins (Aglycones) Umbelliferone (7-hydroxycoumarin) Umbellic acid Herniarin (7-methoxycoumarin) Umbelliferone (7-hydroxyl coumarin) is the lactone of umbellic acid which occurs both in free state and in the form of glycoside in some resins of the umbelliferae family (Ferula asafoetida) Examples of Coumarin glycosides Dauroside A and D have been isolated from the plant Haplophyllum dauricum Linn. family Rutaceae. Chemical test for Coumarin Glycoside Coumarin and its derivatives gives blue or violet fluorescence in aqueous ammoniacal solution. Medicinal uses It has been used as a precursor for many anticoagulants, notably warfarin. Natural coumarins play a significant role in cancer prevention and treatment, haemorrhagic and antifungal activities. Industrial uses They are mostly used in the fragrance (flavouring) industry as an enhancers and stabilizers (but may cause damage to the liver i.e., it may cause hepatotoxicity). They are also used in dyeing due the blue or violet fluorescence they produce in in aqueous ammoniacal solution. Warfarin Asafoetida (Asafetida) Synonyms: Devil’s dung; Food of the gods; Asafoda; Asant; Hing Biological Source: Asafoetida is an oleo-gum resin obtained as an exudation by incision of the decapitated rhizome and roots of Ferula asafoetida L, F. foetida, Royel, F. rubricaulis Boiss, and some other species of Ferula, belonging to family Apiaceae (Umbelliferae). Geographical Source: The plant grows in Iran, Turkestan and Afghanistan Collection The plant is a perennial branching, 3 m high herb possessing large schizogeneous ducts and lysigenous cavities containing milky liquid. Upon exudation and drying of the liquid, Asafoetida is obtained. For the collection of the drug the upper part of the root is laid bare and the stem cut off close to the crown in March–April. The exposed surface is covered by a dome-shaped structure made of twigs and earth. After separating each slice, exudation of oleo- gum-resin, present as whitish gummy resinous emulsion in the schizogenous ducts of the cortex of the stem, takes place. It hardens on the cut surface which is collected, packed in tin-line cases and exported. Removal of the exudation and exposure of fresh surface proceeds until the root is exhausted. The yield is usually soft enough to agglomerate into masses when packed. Chemical Constituents Asafoetida contains volatile oil (4–20%), resin (40–65%), and gum (25%). The garlic-like odour of the oil is due to the presence of sulphur compounds (e.g., isobutyl propanyl disulphide (C 6H16S2). The resin consists of ester of asaresinotannol and ferulic acid, pinene, vanillin and free ferulic acid. On treatment of ferulic acid with hydrochloric acid, it is converted into umbelliferone (a coumarin) which gives blue fluorescence with ammonia. Asafoetida also contains phellandrene, sec-butylpropenyl disulphide, geranyl acetate, bornyl acetate, α-terpineol, myristic acid, camphene, myrcene, limonene, fenchone, eugenol, linalool, geraniol, isoborneol, borneol, guaiacol, cadinol, farnesol, assafoetidin and foetidin. Chemical Tests 1. On trituration with water it produces a milky emulsion. 2. The drug (0.5 g) is boiled with hydrochloric acid (5 ml) for sometimes. It is filtered and ammonia is added to the filtrate. A blue fluorescence is obtained. 3. To the fractured surface add 50% nitric acid. Green colour is produced. 4. To the fractured surface of the drug, add sulphuric acid (1 drop). A red colour is obtained which changes to violet on washing with water. Adulteration Asafoetida is adulterated with gum Arabic, other gum-resins, rosin, gypsum, red clay, chalk, barley or wheat flour, and slices of potatoes. Allied Drugs Galbanum and ammoniacum are oleo-gum-resins obtained, respectively, from Ferula galbaniflua and Dorema ammoniacum. Galbanum contains umbelliferone and umbelliferone ethers, up to 30% of volatile oil containing numerous mono- and sesquiterpenes, azulenes, and sulphur-containing esters. Ammoniacum contains free salicylic acid but no umbeiliferone. The major phenolic constituent is ammoresinol. An epimeric mixture of prenylated chromandiones termed ammodoremin is also present. The volatile oil (0.5%) contains various terpenoids with ferulene as the major component. Medicinal Uses 1-Antioxidant – Scavenges the free radicals 2-Antimicrobial – Fights against microbes 3-Anti-viral – Highly effective against virus 4-Antifungal – Destroys the fungal colony 5-Chemopreventive – Prevents cancer 6-Anti-diabetic – Fight against diabetes 7-Anticarcinogenesis – Stops the cells from developing cancer 8-Antispasmodic – Relaxes the muscles 9-Hypotensive – Lowers the blood pressure Relaxant – 10-Relaxes both mind and body 11-Neuroprotective – Protects the nervous system 12-Molluscicidal – Useful as a pesticide in agriculture 13-Antiasthmatic – Prevents respiratory problems like asthma 14-Antiepileptic – Fights against epilepsy 15-Hepatoprotective – Maintains a healthy liver 16-Antiprotozoal – Destroys the growth of protozoans 17-Antihelminthic – Destroys the helminthic growth 18) carminative, 19) expectorant, 20) antispasmodic, 23) laxative 23) as an enema for intestinal flatulence, 24) in hysterical 24) epileptic affections, 25) in cholera, 26) asthma, 27) whooping cough, and 28) chronic bronchitis. Other uses For flavouring curries, sauces, and pickles (a piece of food and especially a cucumber that has been preserved in a solution of salt water or vinegar Haplophyllum dauricum Biological Source: The genus Haplophyllum belongs to the family Rutaceae. There are more than 70 species. The coumarin glycosides are obtained from the roots and *epigeal parts of Haplophyllum dauricum (L.) G.Don and other species such as Haplophyllum patavinum (L.) G. Don fil. of the family Rutaceae. Geographical source Mediterranean region to eastern Siberia, most of them in western and central Asia, Europe, Italy. Uses They show antitumor activity and others. *Epigeal: Growing on or close to the ground. Galium odoratum - (L.)Scop. Common Name: Sweet Woodruff, Sweet scented bedstraw, Bedstraw Biological source: The coumarin is obtained from the roots and leaves of Galium odoratum of the family Rubiaceae. Synonyms: Asperula odorata Geographical source: Northern and central Europe, including Britain, south and east to N. Africa and Siberia. Chemical constituents: It contains asperuloside (a terpenoid glycopside) and coumarin (a benzopyrone) Medicinal Uses The leaves are antispasmodic, cardiac, diaphoretic, diuretic, and sedative. Both Asperuloside (a terpenoid) and Coumarin (a benzopyrone) occur in some species of Galium. Asperuloside can be converted into prostaglandins (hormone-like compounds that stimulate the uterus and affect blood vessels), making the genus of great interest to the pharmaceutical industry. Other uses A red dye is obtained from the root. Soft-tan and grey-green dyes are obtained from the stems and leaves. Tonka seed Synonyms: Tonka bean camphor; Cumarin; Coumarimic anhydride. Biological Source: It is found in the tonka seed, also known as tonquin beans or tonco seed i.e., Dipteryx odorata Wild, and Dipteryx oppositifolia L., belonging to family Leguminosae. It is also obtained from Woodruff (Asperula species) and in sweet clover i.e.; Melilotus alba Dess., family : Leguminosae. Geographical Source: These plants are found in Europe, India and in the African continent. Chemical constituents: Coumarin Chracteristics Colour : Colourless Odour : Pleasant and fragrant odour resembling that of vanilla beans. Taste : Burning Taste Uses It is mostly employed as a pharmaceutical aid. The seeds can also be used in the treatment of stomach pain, cough, and dysentery. The seeds are used in perfumery and as a vanilla substitute. Hierochloe odorata (L.) P. Beauv. Common names: Sweet Grass, Vanilla Grass Geographical source: It is found in USA, North America. Biological source: The drug comes from the whole part of the plant Hierochloe odorata (L.) P. Beauv. of the family Poaceae (Graminae). Synonym(s): Anthoxanthum nitens, Hierochloe fragrans, Hierochloe nashii, Hierochloe odorata var. fragrans, Holcus odoratus, Savastana nashii, Savastana odorata and Torresia odorata. Description Vanilla grass or sweet grass is an erect, slender, sweet-smelling grass, 12-20 in. tall., with small seed heads bearing broad, bronze-colored spikelets. The grass spreads by creeping rhizomes which send up few to several leafy shoots. This is a perennial plant. This beautiful and quite ethereal grass is characterised by its eponymous sweet scent. Found by riversides, pond and lake margins and other damp spots, it forms dense clumps of intense vanilla-scented, flat, bright green leaves and bears in spring loose panicles of flowers. Chemical constituents It contains contain coumarin and its derivatives 5,8-dihydroxycoumarin and 5-hydroxy-8-O-β-D-glucopyranosycoumarin. Medicinal Uses A tea made from the leaves is used in the treatment of fevers, coughs, sore throats, chafing and venereal infections. It is also used to stop vaginal bleeding and to expel afterbirth. The stems can be soaked in water and used to treat windburn and chapping and as an eyewash. Other uses The leaves have long been used as incense to scent churches on Holy Days and for flavouring a wide variety of food and drink. Many countries, they add a blade or two to their bottles of vodka and other drinks for flavouring. Also, many North American indigenous cultures burn Sweet Grass in ceremonies to invite the presence of good spirits.  FURANOCOUMARINS Introduction Furanocoumarins are toxic compounds that consists of a coumarin nucleus bonded to a furan ring. In furanocoumarins, the furan ring is joined to the coumarin at 6:7 or 7:8 positions. Coumarin Furan Furanocoumarin (Psoralen) Furanocoumarins are primary photodynamic agents. They absorb long-wave, ultra-violet radiation upon exposure of the skin of an animal to sunlight and become photoactive, hence effective in treatment of dermal problems. They then cause cell damage by inhibiting DNA synthesis, by binding pyrimidine bases and nucleic acids. Occurrence in Plants Several plants contain the psoralen (Furanocoumarin) that are generally the precursors of furanocoumarins. Furanocoumarins are found in Rutaceae, Umbelliferae (Apiaceae) and Leguminosae (Fabaceae). They are produce in plants like celery and parsnips in response to fungal infestation.  Furanocoumarin (Psoralen) or Imperatorin Structures of some furanocoumarins and medicinal uses Bavchi Synonyms: Psoralea, Bavchi fruits, Malaya tea, Bavachi seeds Biological source: Bavchi consists of the dried ripe fruits and seeds of Psoralea corylifolia Linn. of the family Leguminosae (Fabaceae). Geographical source: India, China, Srilanka, Nepal, Vietnam. Macroscopy The plant is an annual herb attending to a height of 60 cm to 1 m. The plant contains prominent grooves of the glands and white hairs on the stem and branches. The fruits are very small 3-4.5 mm long and 2-3 mm broad. The fruits are dark chocolate to black in colour with pericarp attached to seeds. Fruits are ovate, oblong or bean shaped. Microscopy A thin section of the fruit shows pericarp with prominent ridges and depressions, consisting of collapsed parenchyma and large secretory glands containing oleoresinous matter. Chemical constituents Bavchi contains coumarin compounds like psoralen, isopsoralen, psoralidin, isopsoralidin, carylifolean, bavachromanol and psoralenol. It also contains fixed oil (10 %), essential oil (0.05%) and resin. The seeds contains flavonoids like bavachalcone, bavachinin, isobavachalcone and others. The seed oil produce some terpenes like limonene, linalool and others. Chemical test Dissolve psoralen in ethanol and then add sodium hydroxide. Observe under UV light; yellow fluorescence is observed. Uses The fruits are aphrodisiac, antibacterial and tonic to the genital organs. The seed is anthelmintic, antibacterial, aphrodisiac, astringent, cytotoxic, diaphoretic, diuretic, stimulant, stomachic and tonic. It is used in treatment of febrile diseases, premature ejaculation, impotence, lower back pains, frequent urination, incontinence, bed wetting. It is also used externally to treat various skin ailments including leprosy, leukoderma and hair loss. Ammi Synonyms: Bishop’s weed, Lace flower, Large Bull wort, Toothpick Ammi Biological source: These are the fruits of Ammi majus Linn. Of the family Umbelliferae (Apiaceae) Geographical source: Europe, Egypt, West Africa and India. Morphology The fruits are 22.5 mm long and 0.5 to 1.7 mm broad. The fruits can be distinguished by the presence of four prominent secondary ridges and by the absence of lacunae outside the vascular bundles, seen in the transverse section of Ammi visnaga. Microscopy: The epidermis of the pericarp consists of polygonal cells, with straight anticlinal walls and short papillae, containing clusters or prismatic crystals of calcium oxalate, and covered with thick strongly striated cuticle; stomata, occasional, of cruciferous type but no hairs. Chemical constituents The drug, contains furanocoumarins, xanthotoxins, imperatorin, bergapten and isopimpilin. Identification test 1. Boil about 1 g of the drug with 10 ml of water for 1 minutes and strain, add 1 or 2 drops of the decoction to 2 mL of a solution of NaOH, no rose colour is produced (distinction form Ammi visinaga). 2. The ethanol extract of the fruit gives blue fluorescence when examined under UV light. Uses The drug contain furanocoumarins which stimulate pigment production in the skin that is exposed to bright sunlight and are used in the treatment of vitiligo (piebald skin) and psoriasis. Visnaga Synonyms: Bishop’s flower, Greater Ammi, Khaizaran, Toothpick weed, Viznaga Biological source: These are fruits of Ammi visnaga Linn. of the family umbelliferae (Apiaceae) Geographical source: Europe, West Asia, Egypt, West Africa Morphology: The fruit , cremocarp, usually separated into its two mesocarps, rarely entire, with a part of pedicel attached. There are other characters. Microscopic characters: The mericarp is an almost regular pentagon and the seeds orthospermous. There are five vascular strands and four vittae; on the outer side of each vittae a group of radiating club shaped cells and these cause a slight elevation of the surface over vitta, thus forming the secondary ridges. It contains a large lacuna on the outer side of each vascular strand in the primary ridges. Chemical constituents: The drug contains furanocoumarin compounds. The main constituents are khellin and visnagin, which are γ-benzopyrone derivatives. Khellol and khellol glucoside are also present. In addition, it contains pyranocoumarin ester visnadin, samidin and dihydrosamidin. Fixed oil and proteins are also present. Chemical test The drug when treated with strong mineral acid shows lemon yellow colour while in Ammi majus dirty green brown colour is seen. Uses Visnaga is an effective muscle relaxant and has been used for centuries to alleviate the excruciating pain of kidney stones. Khellin is used in treatment of asthma. The seeds are diuretic, antiasthmatic and lithontripic. The seeds have strongly antispasmodic action on the smaller bronchial muscle; they dilate the bronchial, urinary and blood vessels without affecting the blood pressure. Bergamot Scientific name: Monarda fistulosa L. other species: Monarda didyma Family: Lamiaceae A herb with so many uses and so pretty with a lovely lemon-orange scent. Chemicals constituents Furanocoumarins and essential oils consisting of terpenes (such as: carvacrol, thymoquinone, Geraniol, geranial, geranyl formate, p-cymene). Culinary Uses Can be scattered in salads or summer drinks. Leaves can be infused in tea (is used for Earl Grey tea). Can be used in stuffing. Lovely for flavouring omlettes, fish and chicken. Medicinal Uses Can relieve nausea, flatulence, menstrual pain and insomia as a tea. Steam inhalation can help bronchial catarrh and sore throats. Has antiseptic properties. Can relax nerves and reduce tension. Induces perspiration so can help reduce fever and easing colds. Can relieve rheumatic aches. Chemical Constituents Bergaptene (5-methoxypsoralen) is a naturally-occurring organic chemical compound produced by numerous plant species, especially from the carrot family Apiaceae and the citrus family Rutaceae. For example, bergapten has been extracted from 24 species of the genus Heracleum in the family Apiaceae. Bergapten (BP) or 5-methoxypsoralen (5-MOP) is a furocoumarin compound mainly found in bergamot essential oil but also in other citrus essential oils and grapefruit juice. Bergaptene WHAT IS PHOTOTOXICITY? Phototoxicity can occur when the constituents of certain Essential oils, namely Furanocoumarins, react when exposed to UV light. This can result in inflammation, blistering, reddening, and burning of the skin. Furanocoumarins are natural chemicals found in certain Essential Oils, specifically Cold-Pressed Citrus Oils. Not all furanocoumarins that are present in Essential Oils are Phototoxic, however, the ones that can cause photosensitivity include Psoralene, methoxsalen, bergaptene, and oxypeucedanin. When high amounts of these components are applied to the skin via topical Essential Oil use, inflammation that is reminiscent of a sunburn can appear on the skin, and in extreme cases, blistering can occur. The side effects of phototoxicity can show up within the first 24 hours after application and peak 36-72 hours after UV exposure, meanwhile any skin discoloration can last up to a few months. Cosmetic Making Bergamot Essential Oil's skincare benefits extend to the realm of cosmetics. It is often used in formulations of natural makeup removers, face serums, and toners. Its astringent properties can help tighten the skin, making it a valuable addition to anti-aging cosmetics. Phototoxicity Concerns It is essential to note that traditional Bergamot Essential Oil can be phototoxic, meaning it can cause skin irritation or hyperpigmentation when exposed to sunlight. As a result, many cosmetic formulations opt for bergaptene-free variants for added safety. The sheer versatility and range of applications of Bergamot Essential Oil make it an invaluable addition to any personal care or cosmetic line. From its enchanting aroma to its therapeutic properties, Bergamot continues to be a cherished natural ingredient for promoting physical and emotional well-being. Furanocoumarins from Aspergillus flavus and Aspergillus parasiticus Aflatoxins are a group of carcinogenic furanocoumarins mainly produced by Aspergillus flavus and Aspergillus parasiticus. These saprophytic fungi are distributed worldwide and are common in the southeastern United States, southern Asia, and Africa, where warm subtropical climates are conducive to fungal growth. Novobiocin is an antibiotic obtained from aflatoxin and is used occasionally as an alternative to penicillins against penicillin-resistant Staphylococcus spp. Novobiocin is an aminocoumarin antibiotic that was produced by the actinomycete Streptomyces niveus. Novobiocin binds to DNA gyrase, and blocks adenosine triphosphatase (ATPase) activity. Other antibiotics in the aminocoumarin class include coumermycin A1 and clorobiocin. Novobiocin PUVA (photochemotherapy) PUVA or photochemotherapy is a type of ultraviolet radiation treatment (phototherapy) used for severe skin diseases. PUVA is a combination treatment which consists of Psoralens (P) (Furanocoumarins) and then exposing the skin to UVA (long wave ultraviolet radiation). It has been available in its present form since 1976. Psoralens are compounds found in many plants which make the skin temporarily sensitive to UVA. The ancient Egyptians were the first to use psoralens for the treatment of skin diseases thousands of years ago. Medicine psoralens include methoxsalen (8-methoxypsoralen), 5-methoxypsoralen and trisoralen. Introduction These are glycosides that produce toxic hydrogen cyanide gas HCN (g) or Hydrocyanic acid as one of their product on hydrolysis. They are widely distributed in the plants of the Rosaceae family. Plant species containing these glycosides are generally very toxic. These glycosides are present in some species of Manihot esculenta (Cassava) and Prunus species (Prunus amygdalus). Amygdalin is an important example of these group of glycoside. Some of the cyanogenetic glycosides have been claimed to possess anticancer properties while and others have demonstrated anti-anaemic activity. Also, preparation from plants containing cyanogenetic glycosides are widely used as flavouring agents. The aglycone moiety of the cyanogenetic glycoside is cyanohydrin of a carbonyl compound (aldehyde or ketone) formed by condensation with HCN or NaCN. The majority of the cyanogenetic glycosides are derivatives of benzaldehyde-cyanohydrin of which amygdalin is an example. Formation of Cyanohydrin a) Benzaldehyde-cyanohydrin (mandelonitrile) + Condensation Glucose HCN H Benzaldehyde (Aldehyde) Hydrogen cyanide Benzaldehyde-cyanohydrin (mandelonitrile) Prunasin (glycoside) b) Acetone-cyanohydrin + HCN Condensation Glucose Acetone-cyanohydrin Linamarin (glycoside) Amygdalin Amygdalin is the most widely distributed cyanophoric glycoside. It occurs several Prunus species and it is obtained from bitter almond (Prunus amygdalus var. amara) of the family Rosaceae. Amygdalin is considered as a gentiobioside of mandelonitrile. Gentiobiose is a reducing disaccharide made of two molecules of glucose linked by β-1,6 linkage. Structure of Amygdalin Gentiobiose part (consists of 2 glucose molecules) Mandelonitrile Hydrolysis of Amygdalin Enzyme hydrolysis The Enzymatic hydrolysis of amygdalin produces the two (2) molecules of glucose and one molecule of mandelonitrile. The mandelonitrile decomposes spontaneously to produce one molecule of benzaldehyde and one molecule of HCN (g). Furthermore, different enzymes act on amygdalin in different ways as follows: Amygdalase Glucose + Prunase Glucose + Benzaldehyde + HCN Prunasin Prunase + Benzaldehyde + HCN Amygdalin Gentiobiose Emulsin or Acid 2 glucose + Benzaldehyde + HCN Prunasin It is a cyanogenetic glycoside obtained from wild cherry bark (Prunus serotina). It contains one glucose unit and a mandelonitrile. Prunasin Detection of Cyanogenetic Glycosides The plant sample is cut into small pieces and then moistened sodium picrate paper (It is prepared by moistening the filter paper with sodium picrate) is then suspended at the neck of the conical flask, the flask is stoppered with cork and then incubated in a warm place at 40 oC for about 30-60 minutes. This is done for the co-existing enzymes to act upon (hydrolyze) the glycoside. This will result in the liberation of HCN (g) which will react with the sodium picrate paper from yellow to brick-red colour. Uses Cyanogenetic glycosides releases hydrogen cyanide i.e. HCN (g). Cyanide glycosides function as defence chemicals because they produce hydrogen cyanide (HCN) which is highly toxic to most living organisms because of its ability to inhibit the electron transport system by binding to cytochromes. Note: Most glycosides remain inactive until they are hydrolysed in the gastric tract by specialized bacteria which then releases an aglycone (e.g., phenols, terpenes, steroids and quinones) that has the active effect. These compounds could be phenols, sulphur or alcohols based and many of them like the cyanogenetic glycosides are extremely toxic. Bitter Almond Synonyms: Almond, Amygdalus Biological source: Bitter almond is the dried ripe seeds of Prunus amygdalus var. amara. of the family Rosaceae Geographical source: Italy, Spain, Morocco, Portugal, Africa Asia and Iran. Chemical constituents: Bitter almond contains amygdalin a colourless crystalline cyanogenrtic glycoside 2.5 % to 4 %, 45 % fixed oil, and proteins 25 % to 30 %. The bitter almond seed also contains a ferment emulsion, which in the presence of water acts on the soluble glucoside amygdalin, producing glucose, prussic acid and essential oil of bitter almonds or benzaldehyde. Uses: It is mainly used as sedative, in bronchitis, vomiting, nausea and conjunctivitis because of hydrocyanic acid. Oil is used as an ingredient in demulcent preparation. Substituents and adulterants Apricot kernels obtained from Prunus armeniaca have their constituents almost similar to that of bitter almond. Amygdalin Wild Cherry Bark Synonyms: Virginian Prune, Black Cherry, Cortex Pruni, Virginian Bark. Biological source: Wild cherry bark is the dried bark of Prunus serotina Ehrhart of the family Rosacaeae. Geographical source: North America. Chemical constituents: It contains prunasin, a cyanogenetic glycoside. Prunasin is hydrolyzed in presence of water by prunase enzyme present in the drug into benzaldehyde, glucose and hydrocyanic acid (HCN). It also contains coumarin derivative scopoletin. It also contain starch, resin, tannin, gallic acid, fatty matter, lignin, red colouring matter, salts of calcium, potassium, and iron, also a volatile oil associated with hydrocyanic acid are present. Prunasin Uses Astringent tonic, pectoral, sedative and expectorant. It is valuable in catarrh, whooping cough and dyspepsia. It has been used in treatment of bronchitis of various types. Substitutes Other north American species of Prunus is occasionally substituted for the genuine wild cherry bark. Cyanogenic Glycosides in Cassava Manihot esculenta Crantz of the spurge family (Euphorbiaceae). It is extensively cultivated in the tropics for its large tuberous roots, the starch wich forms avaluable foodstuff. Cassava accumulates cyanogeneticglycosides linamarin (2-β-glucopyranosyloxy-2-methylpropiononitrile) and lotaustralin [(2R)-2-β- D-glucopyranosyoxy-2-methylbutyronitrile] in roots and leaves. Structures of linamarin and lotaustralin or Linamarin Cassava (Manihot esculenta) is consumed widely in Africa as a food-stuff (Garri) and both the enzymes and cyanide glycosides are present, although extensive boiling of the cassava before eating results in the removal of the toxic HCN. Some cassava are eaten raw, but it highly likely that these are chemical traces of the plant lack either the glycoside or the enzymes, so raw cassava should be avoided if there is doubt about the presence of the toxic compounds. Medicinal uses This food plant is also used medicinally to treat hypertension, headache, and other pains, irritable bowel syndrome and fever. The bitter variety leaves of Manihot esculenta are also used to treat hypertension, headache, and pain. Manihot esculenta (Cassava)  GLUCOSINOLATES Introduction Glucosinolates are natural components of many pungent plants such as white mustard (Brassica alba) and black mustard (Brassica nigra), cabbage (Brassica oleracea), and horseradish (Armoracia rusticana). The pungency of those plants is due to mustard oils produced from glucosinolates when the plant material is chewed, cut, or otherwise damaged. The glucosinolates most likely contribute to the plant’s defence against pests and diseases. The glucosinolates imparts a characteristic bitter flavour property to cruciferous vegetables. The glucosinolates are anions (negatively charged ion) which occur only in the cells of limited number of dicotyledonous families. Glucosinolates have been found in the following dicotyledonous plant families: Cruciferae, Capparidaceae, Resedaceae, Euphorbiaceae, Tovariaceae, Moringaceae, Tropaeolaceae and Caricaceae. General functions These glycosides significantly increase the non-specific resistance of the plants to microorganisms. Glucosinolates have antithyroid and goitre-inducing effect in man. These glycosides are irritant and are used as counter irritants externally in neuralgia, rheumatism, etc. Chemistry of Glucosinolates The glucosinolates are sulphur containing glycosides. Because they contain sulphur, they are therefore referred to as thiocyanate glycosides (Note: thio means sulphur). The best examples of thioglycosides are sinigrin which occur in black mustard and sinalbin which occur in white mustard. Glucosinolates are β-glycosides and are hydrolyzed by the enzyme myrosinase in the presence of water. Sinigrin and sinalbin belongs to this group.  General Structure of Thioglycosides The general structure of thioglycosides is as follows: S Glucose R C NOSO3- X+ Glucosinolate anion This anion is called glucosinolate ion; where R may be aliphatic or aromatic. The cation X+ may be a simple metallic ion (cation) e.g., Na+ or K+ or it can be a complex organic cation e.g., sinalpine cation of sinalbin. Structures of Singrin, Sinalbin and Sinalpine cation Sinalpine cation Hydrolysis of Sinigrin Hydrolysis of sinigrin produces allyl isothiocyanate, potassium acid sulphate and glucose. Allyl isothiocyanate is responsible for the activity of sinigrin as irritant. Hydrolysis of sinalbin Hydrolysis of sinalbin produces phenolic isothiocyanate (Acrinyl isothiocyanate), glucose and the acid sulphate of a quaternary alkaloid; sinalpine. or using the enzyme Myrosinase Isothio Glucose cyanate 4-hydroxyl benzyl Allyl-isothiocyanate Glucose BLACK MUSTARD Synonyms: Black mustard, Brown mustard, Brassica sinapiodes Biological source: Black mustard consists of the seeds of Brassica nigra Linn. or Brassica juncea of the family Cruciferae (Brassicaceae). Geographical source: Europe, South Siberia, Asia Minor and Northern Africa. It is naturalized in North and South America and India. Chemical constituents The active constituents in both mustards is the isothiocyanate glycoside (sinigrin) and the enzyme myrosin which hydrolyses the sinigrin to allyl isothiocyanate in the presence of water. Mustard also contains 30 % fixed oil, 20 % protein and 0.7 to 1.3 % volatile oil. Uses They are used as irritant, stimulant, diuretic and emetic. Mustard oil is a powerful irritant and rubefacient. White Mustard Synonym: Sinapis alba (alba means white) Biological source: White mustard consists of the seeds of Brassica alba Boiss of the Cruciferae (Brassicaceae) Geographical source: Europe and England. Chemical constituents The seeds contain the crystalline isothiocyanate glycoside Sinalbin and the enzyme Myrosin. It also contains about 25 % fixed oil. Uses An infusion of the seeds will relieve chronic bronchitis, digestive disorders and rheumatism. Other Plants Containing Glucosinolates 1. Cabbage (Brassica oleracea) Cabbage, (Brassica oleracea), vegetable and fodder plant of the mustard family (Brassicaceae), the various agricultural forms of which have been developed by long cultivation from the wild cabbage (Brassica oleracea). The edible portions of all cabbage forms—which include: kale, broccoli, and Brussels sprouts—are low in calories and are an excellent source of vitamin C. Head cabbage, generally designated simply “cabbage,” is a major table vegetable in most countries of the temperate zone. Chemical constituents of Cabbage The internal leaves contains the following acids: aconitic, citric, ascorbic, malic, quinic, shikimic and fumaric acids. Cabbage contains considerable amounts of bioactive compounds such as glucosinolates (Gluconapin), vitamin C, carotenoids, and polyphenols Uses/ medicinal uses It is widely consume as vegetable. table. People also use the leaves for medicine. Cabbage is used for stomach pain, excess stomach acid, stomach and intestinal ulcers, and a stomach condition called Roemheld syndrome. Cabbage is also used to treat asthma and morning sickness.