Pharmacognosy 1 PDF
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St. Augustine University of Tanzania
Dr. Sartaj Begum
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This document provides a basic introduction to pharmacognosy, a science that studies crude medicines obtained from natural sources, primarily plants and animals. It explores the historical development of pharmacognosy, tracing the use of plants for medicinal purposes from early humans to modern medicine. The text also discusses the various sources of crude drugs, their uses in medicine, cosmetics, and research, and their role in drug discovery.
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BASIC INTRODUCTION TO PHARMACOGNOSY BY DR. SARTAJ BEGUM WHAT IS PHARMACOGNOSY? Is a science which deals with the study of crude medicine in substances obtained from natural sources mainly plant and animal. Crude medicine; are drugs which are from plant or animal not processed (no...
BASIC INTRODUCTION TO PHARMACOGNOSY BY DR. SARTAJ BEGUM WHAT IS PHARMACOGNOSY? Is a science which deals with the study of crude medicine in substances obtained from natural sources mainly plant and animal. Crude medicine; are drugs which are from plant or animal not processed (no any addition to add potency) The word "Pharmacognosy" derived from the Greek words "Pharmakon” –a drug, or medicine "gignosis” –to acquire knowledge of It deals with scientific study of structural, physical, chemical and sensory characters of crude drug obtained from plant, animal and mineral sources. Therefore:Pharmacognosy is “an applied science that deals with the biological, biochemical and economic features of natural crude drugs and their active constituents (derivatives)”. ◘ Pharmacognosy does not include the study of synthetic drugs. ◘ Pharmacognosy is NOT identical to Medicinal Chemistry and/or Pharmacology but utilizes their methods. ◘ Studies drugs from plants, animals and minerals E.g.: Digitalis leaf & its glycosides (digitoxin) Rauwolfia root & its alklaoids (reserpine) Thyroid gland & its extracted hormone (thyroxin) Pharmacognosy is not confined to plants BUT also investigates biodynamic compounds in animals, marine organisms, fungi, and micro- organisms NOTE: Natural drug constituents which have been prepared synthetically (e.g. ephedrine, vanillin, caffeine, codeine, menthol, penicillin) BOTH natural and synthetic substances are considered a definite part of pharmacognosy. Pharmacognosy “derived from the Greek Pharmacon, a drug, and Gignosis which means acquire knowledge. Pharmacognosy is the study of crude drugs obtained from plants, animals and mineral kingdom Crude drugs :Are those natural products such as plants or part of plants, extracts and exudates which are not pure compounds and used in medicine 6 HISTORICAL DEVELOPMENT OF PHARMACOGNOSY Pharmacognosy is regarded as the mother of all science. History of pharmacognosy represents the history of pharmacy & medicine. Pharmacognosy had its origin in the health-related activities of the most primitive human race of the remote past. The early man sought to alleviate his sufferings of illness & injuries by using plants. 7 HISTORY OF PHARMACOGNOSY----- They acquired knowledge of medicinal properties of plants in the following way: By guesswork or trial & error While searching for food By superficial resemblance between the plant parts & the affected organs, that is, by examining the “Signature of Nature”. By observing other animals instinctive discrimination between toxic & palatable plants By accidental discovery (SERENDIPITY) 8 HISTORY OF PHARMACOGNOSY----- By a combination of all these means the ancient people acquired a considerable volume of knowledge about drugs. In course of time a group of people emerged in each community who acquired expertise in collecting, testing & using medicinal plants for treating diseases. These people later became known as `Medicine Men'. The Medicine Men monopolized the knowledge of drugs and hide that knowledge in some mysterious incantations. 9 HISTORY OF PHARMACOGNOSY----- They transferred this secret knowledge only to their trusted predecessors of the successive generations, who gradually increased the volume of knowledge about drugs and their uses. Initially the transfer of the acquired knowledge from generation to generation used to be done verbally by the use of signs & symbols. As civilization progressed, transfer and recording of the knowledge were done in writing. 10 HISTORY OF PHARMACOGNOSY----- The use of plants, plant extracts or pure chemicals isolated form natural products to treat disease is a therapeutic modality, which has stood the test of time even if much of the science behind such therapy is still in its infancy. Indeed today many pharmacological classes of drugs include a natural product prototype. 11 HISTORICAL DEVELOPMENT OF PHARMACOGNOSY With increase of knowledge of drugs, the volume of works also increased a lot and it become impossible for one person to manage them properly. Thus at this point pharmacy and medicine started to develop along two separate paths One group specialized in diagnosing the disease and prescribing the drug known as phyisician or doctors The other group specialized in collection , processing ,preparation and collection of medicaments knows as pharmacist,. HISTORICAL DEVELOPMENT OF PHARMACOGNOSY From the earliest times man and animals have had to distinguish from those plants which are poisonous and those which are not. While pharmacognosy is mainly concerned with natural occurring substances having a medicinal action, it is not entirely limited to such substances only but also to natural, synthetic fibers and the surgical dressings prepared from them. Also includes the study of other materials used in pharmacy, such as flavoring agents, suspending agents, disintegrants, filtering and support media etc. HISTORICAL DEVELOPMENT OF PHARMACOGNOSY Other fields which have natural associations with the subject are those of poisonous and hallucinogenic plants, raw materials for production of oral contraceptives, allergens, herbicides and insecticides. Pharmacognosy is closely related to both botany and plant chemistry, being particularly concerned with the description and identification of drugs both in whole state, powder form and with their history, commerce, collection, preparation, evaluation, preservation and storage. Undoubtedly the plant kingdom still holds many species of plants containing substances of medicinal value which have not yet be discovered. HISTORICAL DEVELOPMENT OF PHARMACOGNOSY As a result of Modern isolation and pharmacological testing procedures, new plant drugs usually find their way into medicine as purified substances rather than in the form of older galenical preparation. Thus, there came to be three basic disciplines devoted to drugs; ▪Pharmacology – This dealt with drug actions and effects. ▪Pharmacognosy – covering all information on medicines from natural sources i.e. plants, animals and microorganisms. ▪Medicinal chemistry – the science of synthetic drugs. NATURALLY OCCURRING SUBSTANCES HAVING A MEDICINAL ACTION: Surgical dressings prepared from natural fibres Flavourings and suspending agents Disintegrants Filtering and support media Other associated fields: Poisonous and hallucinogenic plants Raw materials for production of oral contraceptives Allergens Herbicides and insecticides 16 PHARMACOGNOSY IS RELATED TO: Botany Ethnobotany Marine biology Microbiology Herbal medicine Chemistry (phytochemistry) Pharmacology Pharmaceutics 17 WHY DO WE NEED PLANTS? 1. Source of drug molecules Most drugs can be synthesised Still more economical to use the plant Papaver opium -> morphine, codeine (strong medicinal pain) Ergot fungus –> ergotamine (headache), ergometrine (direct action on uterine muscle) 18 DIGITALIS FOXGLOVE -> DIGOXIN (ACTS ON CARDIAC MUSCLE) 19 Source of complex molecules that can be 2. modified to medicinal compounds Examples: Dioscera yam: molecule -> steroids Soya: saponins -> steroids 20 3. Source of toxic molecules To study the way the body responds to their pharmacological use Investigating pharmacological mechanisms picrotoxin – nerve conduction 21 CONCLUSION ✓Natural products very important to medicine ✓Exist in range of structures that one wouldn’t think of synthesizing ✓Can act as templates for new drug development ✓Untapped reservoir of new compounds 22 INTRODUCTION TO NATURAL PRODUCTS ▪A brief history of natural products in medicine ▪Value of natural drug products ▪Production of natural drug products ▪The role of natural products in drug discovery ▪General principles of botany: morphology and systematics I. THE HISTORY OF NATURAL PRODUCTS IN MEDICINE ▪A great proportion of the natural products used as drugs ▪The study of drugs used by traditional healers is an important object of pharmacognostical research ▪Sumerians and Akkadians (3rd millennium BC) EGYPTIANS (EBERS PAPYRUS , 1550 BC) AUTHORS OF ANTIQUITY HIPPOCRATES (460-377 BC) “THE FATHER OF MEDICINE” DIOSCORIDES (40-80 AD) “DE MATERIA MEDICA” (600 MEDICINAL PLANTS) THE ISLAMIC ERA IBN ALTABARI (770−850) “” فردوس الحكمه )IBN SINA (980-1037 ” القانون في الطب“ )IBN ALBITAR (1148-1197 ” الجامع لمفردات األدوية واألغذية“ THE ERA OF EUROPEAN EXPLORATION OVERSEAS (16TH AND 17 TH CENTURY) THE 18TH CENTURY, PHARMACOGNOSY ▪Johann Adam (1759-1809) ▪Linnaeus (naming and classifying plants) ▪At the end of the 18th century, crude drugs were still being used as powders, simple extracts, or tinctures THE ERA OF PURE COMPOUNDS (IN 1803, A NEW ERA IN THE HISTORY OF MEDICINE) Isolation of morphine from opium Strychnine (1817) Quinine and caffeine (1820) Nicotine (1828) Atropine (1833) Cocaine (1855) In the 19th century, the chemical structures of many of the isolated compounds were determined In the 20th century, the discovery of important drugs from the animal kingdom, particularly hormones and vitamins. Microorganisms have become a very important source of drugs CRUDE DRUGS Also,means any product that has not been advanced in value or improved in condition by grinding, chipping, crushing, distilling, evaporating, extracting, artificial mixing with other substance or by any other process or treatment beyond what is essential to its proper packing and the prevention of decay or deterioration pending manufacture. 36 Today, Crude drugs are rarely used as therapeutic agents; more often their chief principles (derivatives or extractives which contains active constituents) are separated by various means. Sources of Crude Drugs: Plant sources, e.g. Senna,Digitalis,Datura, Cascara, Cinchona, Clove, Opium, etc. Animal sources, e.g. cochineal, cantharidin, honey, cod liver oil, musk, thyroxin, etc. Mineral sources, e.g. talc, kaolin, kieselguhr, etc. 37 WHAT IS A NATURAL PRODUCT? A natural product is a substance obtained from a natural source. 1. A crude drug , e.g. Senna, Cascara, Cinchona, etc.. 2. A galenical preparation of a crude drug, e.g. extracts and tinctures, etc.. 3. A pure compound, e.g. morphine, atropine, digoxin, etc.. 4. A semithynthetic product, e.g. etoposide, teniposide, hyoscine butyl bromide etc.. 38 USES OF NATURAL PRODUCTS: 1.As drugs for the treatment of a wide range of diseases, e.g. morphine, atropine, digoxin, hormones, antibiotics, etc.. 2.As pharmaceutical aids in pharmaceutical industry e.g. suspending & emulsifying agents, suppository bases, binders, sweetening & colouring agents, etc.. 39 USES OF NATURAL PRODUCTS: 3. In cosmetics as flavouring & colouring agents, etc. 4. In culture media for the propagation of micro- organisms in microbiology laboratories & biotechnology. 5. General uses e.g. in food industries: as dusting powders, as indicators and in perfumery. 40 DEFINITIONS Pharmacognosy: It is the science of biogenic or nature-derived pharmaceuticals and poisons Crude drugs: It is used for those natural products such as plants or part of plants, extracts and exudates which are not pure compounds Ethnobotany: It is a broad term referring to the study of plants by humans Ethnomedicine: It refers to the use of plants by humans as medicine Traditional medicine: It is the sum total of all non-mainstream medical practices, usually excluding so called “western” medicine Natural products: they can be 1. Entire organism (plant, animal, organism) 2. Part of an organism (a leaf or flower of a plant, an isolated gland or other organ of an animal) 3. An extract or an exudate of an organism 4. Isolated pure compounds TYPES OF DRUGS DERIVED FROM PLANTS 1. Herbal drugs, derived from specific parts of a medicinal plant 2. Compounds isolated from nature 3. Nutraceuticals, or “functional foods” II. VALUE OF NATURAL PRODUCTS Compounds from natural sources play four significant roles in modern medicine: 1. They provide a number of extremely useful drugs that are difficult, if not impossible, to produce commercially by synthetic means 2. Natural sources also supply basic compounds that may be modified slightly to render them more effective or less toxic 3. THEIR UTILITY AS PROTOTYPES OR MODELS FOR SYNTHETIC DRUGS POSSESSING PHYSIOLOGIC ACTIVITIES SIMILAR TO THE ORIGINALS H3C COOH COOH COOH Ibuprofen HO H3 C O O Salicylic Acid Aspirin CH3 CH3 4. 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 Baccatin III → Taxol III. PRODUCTION OF NATURAL DRUG PRODUCTS 1. Collection (wild) 2. Cultivation (commercial), collection, harvesting, drying, garbling, packaging, storage and preservation e.g. ginseng, ginkgo, peppermint 3. Fermentation (Recombinant DNA technology or Genetically engineered drugs) 4. Cell-culture techniques 5. Microbial transformation 6. Biologics (prepared from the blood of animals) IV. THE ROLE OF NATURAL PRODUCTS IN DRUG DISCOVERY 1. Combinatorial chemistry 2. High-throughput screening of natural products 3. Combinatorial biosynthesis 4. Ethnopharmacology V. GENERAL PRINCIPLES OF BOTANY: MORPHOLOGY AND SYSTEMATICS How to define a pharmaceutical plant-derived drug from the botanical point of view ? a botanical drug is a product that is either: Derived from a plant and transformed into a drug by drying certain plant parts, or sometimes the whole plant, or 1. Obtained from a plant, but no longer retains the structure of the plant or its organs and contains a complex mixture of biogenic compounds (e.g. fatty and essential oils, gums, resins, balms) ISOLATED PURE NATURAL PRODUCTS ARE THUS NOT “BOTANICAL DRUGS”, BUT RATHER CHEMICALLY DEFINED DRUGS DERIVED FROM NATURE. ◆ the following plant organs are the most important, with the Latin name that is used, for example in international trade, in parentheses: 1. Aerial parts or herb (herba) 2. Leaf (folia) 3. Flower (flos) 4. Fruit (fructus) 5. Bark (cortex) 6. Root (radix) 7. Rhizome (rhizoma) 8. Bulb (bulbus) The large majority of botanical drugs in current use are derived from leaves or aerial parts. A plant-derived drug should be defined not only in terms of the species from which it is obtained but also the plant part that is used to produce the dried product. Thus, a drug is considered to be adulterated if the wrong plant parts are included (e.g. aerial parts instead of leaves) TAXONOMY It is the science of naming organisms and their correct integration into the existing system of nomenclature The names of species are given in binomial form: the first part of the name indicates the wider taxonomic group, the genus; the second part of the name is the species. PAPAVER SOMNIFERUM L. Species: somniferum, here meaning ‘sleep-producing’ Genus: Papaver (a group of species, in this case poppies, which are closely related) Family: Papaveraceae (a group of genera sharing certain traits) L.: indicates the botanist who provided the first scientific description of the species and who assigned the botanical name MORPHOLOGY OF HIGHER PLANTS 1. Flower It is the essential reproductive organ of a plant. For an inexperienced observer, two characteristics of a flower are particularly noteworthy: the size and the color Although the flowers are of great botanical importance, they are only a minor source of drugs used in phytotherapy or pharmacy e.g. chamomile, Matricaria recutita L. (Asteraceae ) 2. Fruit and seed The lower plants, such as algae, mosses and ferns, do not produce seeds Gymnosperm and Angiosperm Gymnosperm: they are characterized by seeds that are not covered by a secondary outer protective layer, but only by the testa – the seed’s outer layer Angiosperm: the seeds are covered with a specialized organ (the carpels) which in turn develop into the pericarp. Drugs from the fruit thus have to be derived from an angiosperm species Fruits and seeds have yielded important phytotherapeutic products, including: Fruit Caraway, Carum carvi L. (Umbelliferae) Seed (white) mustard, Sinapis alba L. (Brassicaceae) 3. Leaves The function of the leaves, as collectors of the sun’s energy and its assimilation, results in their typical general anatomy with a petiole (stem) and a lamina (blade) A key characteristic of a species is the way in which the leaves are arranged on the stem, they may be: 1. Alternate 2. Distichous 3. Opposite 4. Decussate 5. Whorled The form and size of leaves are essential characteristics e.g. oval, oblong, obovate, rounded, linear, lanceolate, elliptic, spatulate, cordate, hastate or tendril The margin of the leaf is another characteristic feature e.g. entire, serrate, dentate, sinuate, ciliate or spinose Numerous drugs contain leaf material as the main component. e.g. Deadly nightshade, Atropa belladonna L. (Solanaceae) 4. Bark The bark as an outer protective layer frequently accumulates biologically active substances e.g. Red cinchona, Cinchona succirubra L. (Rubiaceae) No stem-derived drug is currently of major importance 5. Rhizome and root drugs Underground organs of only a few species have yielded pharmaceutically important drugs e.g. 1. Sarsaparilla, Smilax regelii (Smilacaceae) 2. Korean ginseng, Panax ginseng (Araliaceae) 6. The bulbs and exudates 1. Garlic, Allium sativum L. (Liliaceae) 2. Aloe vera L. (Asphodelaceae) UNIT-II. Brief introduction to natural sources of drugs with examples: - Plant Source, - Animal Source, - Mineral Source, - Marine Source and - Microorganisms. ▪ A large number of drugs are used in the clinics for the cure of various ailments. ▪ These drugs are diverse in chemical structure and are obtained from a wide variety of sources. ▪ In earlier days, simple chemical substances and different parts of plants were employed as medicinal agents, but most drugs currently used in therapeutics are synthetic in nature. ▪ However, natural sources are still used for obtaining some drugs mainly because their synthesis is difficult and uneconomical. Drugs are mainly obtained from following sources. - Plant Source, - Animal Source, - Mineral Source, - Marine Source and - Microorganisms. SOURCES I. NATURAL SOURCE A. Organic drugs. Organic drugs are mainly obtained from 1. Plant source 2. Animal source 3. Marine sources 4. Microorganisms. B. Inorganic drugs. These are mainly obtained from 1. Metallic source 2. Non-metallic source. II. SYNTHETIC SOURCE (I) NATURAL SOURCES OF DRUGS Active principles of drugs are mainly present in crude form in minute amounts. These active principles are separated by various techniques or may be used as such in some cases. (A) Organic drugs: Main natural sources of organic drugs are plants, animals and microorganisms. 1. Plant source: Plant sources Almost all parts of the plants are used i.e. leaves, stem, bark, fruits and roots. 1. Leaves The leaves of Digitalis purpurea are the source of Digitoxin and Digoxin, which are cardiac glycosides. Leaves of Eucalyptus give oil of Eucalyptus, which is important component of cough syrup. Tobacco leaves give nicotine. Atropa belladonna gives atropine. 2. Flowers Papaver somniferum gives morphine (opoid) Rose gives rose water, used as tonic 3. Fruits Senna pod gives anthracine, which is a purgative (used in constipation) Calabar beans give physostigmine, which is cholinomimetic agent 4. Seeds Seeds of Nux vomica give strychnine, which is a CNS stimulant. Castor seeds give castor oil. Calabar beans give Physostigmine, which is a cholinomimetic drug 5. Roots Ipecacuanha root gives Emetine, used to induce vomiting as in accidental poisoning. It also has amoebicidal properties. Rauwolfia serpentina gives reserpine, a hypotensive agent. Reserpine was used for hypertension treatment. 6. Bark Cinchona bark gives quinine and quinidine, which are antimalarial drugs Quinidine also has antiarrythmic properties. Atropa belladonna gives atropine, which is anticholinergic. Hyoscyamus niger gives Hyosine, which is also anticholinergic 7. Stem Chondrodendron tomentosum gives tuboqurarine, which is skeletal muscle relaxant used in general anesthesia It is very old and important source of drugs, various parts of the plants are still used for drugs. The following table summarizes some Part of the plant Name of the plant Active Principle Use Root Rauwolfia Reserpine Antihypertensive pecacuanha Ipecac Emetic Bulbs Urginea Squill Emetic, rodenticide Bark Cinchona Quinine Antimalarial Rhizome Ginger Gingerol Carminative Wood Sandal wood Sandal wood oil Urinary antiseptic Quassia Quassin Stomachic Leave Belladona Atropine Anti-muscarinic Digitalis Digitoxin Cardiac stimulant Flower Clove Eugenol Local anaesthetic, rubefacient Pyrethrium Pyrethrin Insecticide Fruit Senna Senegrin Purgative Anise Anethole Carminative Seed Nux vomica Strychnine Rodenticide Physostigma Physostigmine Anti-glaucoma Corn Colchicum Colchicine Anti-gout 2. Animal sources : From animal source relatively few but important drugs are obtained. Following are some useful drugs: Hormones: Insulin, thyroxin, gonadotropins, etc. Vitamins: Cod liver oil (vit. A). Vaccines/serra: Anti-rabies vaccine (A.R.V), antitetanic serum (A.T.S), anti- diphtheric serum, etc. Replacement therapy : Liver extract. Animal Sources Pancreas is a source of Insulin, used in treatment of Diabetes. Urine of pregnant women gives human chorionic gonadotropin (HCG) used for the treatment of infertility. Sheep thyroid is a source of thyroxin, used in hypertension. Cod liver is used as a source of vitamin A and D. Anterior pituitary is a source of pituitary gonadotropins, used in treatment of infertility. Blood of animals is used in preparation of vaccines. Stomach tissue contains pepsin and trypsin, which are digestive juices used in treatment of peptic diseases in the past. Nowadays better drugs have replaced them. 3. Marine sources Algae, the chlorophyll containing organisms known to have more than 20 000 species. The multicellular plants growing in salt or fresh water are known as Macro-algae or “seaweeds”. Due to their fast growing nature, they can size up to 60 m in length. Based on their pigmentation they are classified into three broad groups: i) brown seaweed (Phaeophyceae); ii) red seaweed (Rhodophyceae) and iii) green seaweed (Chlorophyceae) APPLICATIONS 1. Hydrocolloids Alginates from the cell wall of brown algae are polymers composed of D- mannuronic acid and L-guluronic acid monomers are used in food and pharmaceutical industries in the form of stabilizers for emulsions and suspensions Carrageenans from the cell wall of red algae have application in food, textile and pharmaceutical industries 2. Pharmaceuticals and cosmetics The micro-algae can produce bioactive compounds like antibiotics, algicides, toxins. A lot of antibiotics have been isolated from algae and show great chemical diversity (fatty acids, bromophenols, tannins, terpenoids, polysaccharides, alcohols). Most of them produce neurotoxic and hepatotoxic compounds Chlorella and Arthrospira (Spirulina) are used in skin care, sun protection and hair care products Agar is used as a thickening and water-binding agent as well as an antioxidant 2. Pharmaceuticals and cosmetics (cont.) As it is rich in vitamins and minerals, algae conditions and hydrates the skin while it nourishes, rejuvenates, detoxifies and replenishes minerals. The important form like Irish moss and carrageenan contain proteins, vitamin A, sugar, starch, vitamin B1, iron, sodium, phosphorous, magnesium, copper and calcium Algae products used as anticoagulants, antibiotics, antihypertensive agents, blood cholesterol reducers, dilatory agents, insecticides, and anti-tumorigenic agents. In cosmetics, algae products act as thickening agents, water-binding agents and antioxidants Microalgae Chlorella, Astaxhanthin and Spirulina have been found to possess anti-cancer, immune stimulatory, detoxifying, anti-diabetic, anti- inflammatory, antihypertensive and digestive properties Caulerpin in Red and Green algae control inflammation while sulphated polysaccharide act as pro-inflammatory. The fucodans, sulphated polysaccharide, of brown algae origin is also anti- inflammatory. The versatility of the green algae Chlamydomonas reinhardtii studied for the utilization in the drug industry. In the study it was found that it produced proteins at very high levels 4. High value oils Long-chain poly-unsaturated fatty acids (vlcPUFAs) eicosapentaenoic (EPA), docosahexaenoic acid (DHA) and arachidonic acid (AA) known for their nutritional importance. Interestingly the vlcPUFAs in the oil-rich fish originate from marine micro-algae that are eaten by the fish. Algal genes encoding relevant enzymes have been identified and recently several groups have reported progress on using these genes to produce DHA and ARA in transgenic plants, including crops such as soybean, linseed, tobacco and the model species Arabidopsis. By adding additional genes to the ones that are needed to produce ARA and EPA, production of DHA has been established in soybean, Brassica juncea and Arabidopsis. An alternative approach is to use directly the algae that are the most efficient primary producers of the vlcPUFAs. 5. Colourants Micro-algae produce carotenoids. More than 40 carotene and xanthophylls are well characterized. Xanthophyll a lutein has a huge application in the colouration of drugs and cosmetics. Phycobillins or phycobiliproteins are water soluble pigments, have their applications in cell biology as fluorescent markers, while the Phycobilins are also used as colorants for food and cosmetic products like a blue phycobilin from Arthrospira is used to colour cosmetics and food 6. Removal of heavy metals Algal biomass used as an inexpensive biomaterial for removal of toxic heavy metals. The use of micro algae for removal of heavy metals from waste water have huge application 7. Food Supplement As microalgae possess high-quality natural proteins, lipids, carbohydrates, vitamins, pigments and enzymes and therefore they can be used as food supplement at commercial levels. Omega-3 fatty acid extracted from algae are used as economical food supplement The edible seaweeds can be used as food supplement due to low calorie, high concentration of minerals, vitamins and proteins and low fat content. Blue green algae Spirulina as rich source of vitamin and minerals is used in food industry 7. Food Supplement (cont.) Several algae in red algae category like Porphyra and brown algae are directly consumed by human beings. Moreover the algae used in animals as food supplement is also an achievement. 8. As Human Food Some red algae, brown algae and green algae, are eaten by humans. Approximately 500 species are eaten by humans, and some 160 are commercially important. The red algae Porphyra is the most important commercial food algae. Palmaria palmata, another red algae, is eaten in the North Atlantic region. Laminaria species (brown algae) is eaten with meat or fish and in soups. The green algae Monostroma and Ulva look like lettuce leaves (their common name is sea lettuce), and they are eaten as salads or in soups, relishes, and meat or fish dishes. The microscopic, freshwater green algae Chlorella is cultivated and eaten in Taiwan, Japan, Malaysia, and the Philippines. It has a high protein content (53–65%) and has been considered as a possible food source during extended space Travel 9. Texturized vegetable protein The invention of digestible texturized algal protein, TAP, will ignite the use of algae in foods. TAP, Alnuts, Nostoc or other trade names may be used as a meat replacement or supplement. The extrusion technology changes the structure of the protein and yields a fibrous spongy matrix that is similar in texture to meat. TAP may be presented in a wide variety of traditional food forms such as sushi, diced chicken, turkey, tuna or red meats 10. HIV Vaccine model In the recent research it is found that algae-based proteins can inhibit the entry of the HIV virus. HIV vaccine grown in a designer strain of algae may be used with the defective cell wall technique to assure transgenic material does not escape into the environment. The vaccine cost would be lower as the algal production would be done locally. Instead of extracting the vaccine, people could eat the algae directly and let their bodies metabolize the vaccine. The same process may work for other vaccines such as mumps, measles, malaria, polio, tuberculosis and other preventable illnesses. There are many obstacles to the vaccine scenario, including bioethics, biotechnology and socio-culture issues. However, the simplicity and cost effectiveness of an algae solution would seem to make algae based vaccine model happen sooner rather than later 11. Personalized Drugs When markers are developed for personalized diagnosis, scientist will need drugs manufactured specifically to match the genetic needs of each patient and they are likely to need the drugs quickly. Personalized drugs and advanced compounds grown in algae may provide a cost effective solution. Such a production system could produce the designer drugs in days instead of months. While there is a critical global need for micro-algaculture systems, large scale systems are needed too 12. Food Additives The cell walls of many types of seaweed contain phycocolloids that have received increasing use in prepared foods. The three major phycocolloids are alginates, agars, and carrageenans. Alginates are extracted primarily from brown seaweeds, and agar and carrageenan are extracted from red seaweeds. Phycocolloids are safely consumed by humans and other animals and are therefore used in a wide variety of prepared foods, such as “ready-mix” cakes, “instant” puddings and pie fillings, and artificial dairy toppings 12. Food Additives (cont.) Alginates, or alginic acids, are commercially extracted from brown seaweeds, especially the kelp Macrocystis, Laminaria, and Ascophyllum. Alginates are used in ice creams to limit ice crystal formation, thereby producing a smooth texture, and are also used as emulsifiers and thickeners in syrups and as fillers in candy bars and salad dressings. Agars are extracted primarily from species of the red alga Gelidium, but they are also obtained from other red algae, especially Gracilaria, Pterocladia, Acanthopeltis, and Ahnfeltia. Agars are used in instant pie fillings, canned meats or fish, and bakery icings. Agar is also used as a clarifying agent in beer and wine. Carrageenan, from the Irish word “carraigin” (meaning Irish moss), are extracted from various red algae: Eucheuma in the Philippines, Chondrus crispus in the United States and the Canadian Maritime Provinces, and Iridaea in Chile. Carrageenans are used as thickening and stabilizing agents in dairy products, imitation creams, puddings, syrups, and canned pet foods. 12. Active Additives in Medical Drugs or Insecticides Phycocolloids have industrial uses in addition to their important roles in food products. Because they are relatively inert and have good gelling properties, they are used as creams and gels for carrying minute amounts of active additives, as in medical drugs or insecticides. Agar is used extensively as a bacteriologic culturing substrate in medical and research facilities and is also used as a substrate for eukaryotic cell and tissue culture, including the culture of algae themselves. Carrageenans are used in the manufacture of shampoos, cosmetics, and Medicines 13. Industrial Chemicals Algae are used for production or extraction of some important chemical that have wide industrial values. Iodine can be extracted from brown algae. The green unicellular flagellate Dunaliella is cultivated in saline ponds. The culture conditions are manipulated so that carotene or glycerol is produced in large amounts. These compounds are extracted and sold commercially. 14. Forensic Medicine Diatoms have been used in forensic medicine. Where death by drowning is suspected, lung tissue is examined. The presence of silica diatom cell walls can verify death by drowning; in mysterious cases, the diatom species can be used to pinpoint the exact location of death because the species are characteristic for a given lake, bog, or bay 4. Microorganisms : Microorganisms are also an important source of drugs. Certain bacteria, fungi and actinomycetes produce antibiotics which forms a major group of therapeutically useful drugs. Fungi : Penicillin G from Penicillium notatum. Actinomycetes : Streptomycin from Streptomyces griseus Bacteria : Bacitracin from Bacillus subtilus. Bacterial sources of drugs Tetracycline Produced by filamentous bacteria-Actinomyces- mainly the mutants of Streptomyces aureofaciens - components of the soil Oxytetracycline -related analogue from S. rimosus Anthracyclic cpds Anti-tumour agents Minocycline and doxycycline-produced synthetically from natural tetracyclines Erythromycin A for Legionnaires’ disease(pneumonia) From Saccharopolyspora erythrea (Actinomycete) Clarithromycin & azithromycin- synthetic analogues The Statins Mevastatin -inhibits cholesterol synthesis; produced by Penicillium citrimum and Penicillium brevicompactum Lovostatin (methyl analogue)-from Monaseus ruber and Aspergillus terreus Simvastatin (Zocor)-dimethyl analogy of Mevastatin All are pro-drugs activated by hydrolysis Pravastatin (Lipostat)-semi synthetically produced by microbial hydrolysis of Mevastatin by Streptomyces carbophilus Bacterial sources of drugs(cont.) Actinobacteria give Streptomycin Aminoglycosides such as gentamycin and tobramycin are obtained from Streptomyces and micromonosporas Vaccines PHARMACETICAL IMPORTANCE OF FUNGI 1. Introduction Cultivated or gathered for food Nutrition Mushrooms are a low-calorie food usually eaten cooked or raw and as garnish to a meal. Dietary mushrooms are a good source of B vitamins, such as riboflavin, niacin and pantothenic acid, and the essential minerals, selenium, copper and potassium. Fat, carbohydrate and calorie content are low, with absence of vitamin C and sodium. There are approximately 20 calories in an ounce of mushrooms Fungi have medicinal properties too Medicinal value Pleurotus ostreatus (oyster mushrooms) Pleurotus ostreatus (oyster mushrooms) The chemical nature of the bioactive compounds present in this mushroom includes: Polysaccharides, Lipopolysaccharides, Proteins, Peptides, Glycoproteins, Nucleosides, Triterpenoids, Lectins, Lipids and their derivatives Pleurotus ostreatus (oyster mushrooms) Pharmacological Activities Antineoplastic (inhibiting or preventing the growth and spread of tumors or malignant cells) Antiviral Antitumor Antimicrobial Antimutagenic Antilipidemic Hypocholesterolemic Immunomodulatory Hepatoprotective Anti-Inflammatory Aspergillus niger Aspergillus niger-industrial and medicinal uses Industrial preparation of citric acid (E330) and gluconic acid (E574) and have been assessed as acceptable for daily intake by the World Health Organisation A. niger fermentation is "generally recognized as safe" (GRAS) by the United States Food and Drug Administration under the Federal Food, Drug, and Cosmetic Act. Many useful enzymes are produced using industrial fermentation of A. niger. For example, A. niger glucoamylase is used in the production of high fructose corn syrup, and pectinases are used in cider and wine clarification. Alpha-galactosidase, an enzyme that breaks down certain complex sugars, is a component of Beano and other products that decrease flatulence (marked by or affected with gases generated in the intestine or stomach) Another use for A. niger within the biotechnology industry is in the production of magnetic isotope-containing variants of biological macromolecules for NMR analysis. Penicillium notatum/Penicillium chrysogenum Source of penicillin discovered by Alexander Fleming Griseofulvin ( Grisovin) Produced by fungus mould Penicillium griseofulvum Systemic treatment of fungal dermatophytic infections for the skin, hair, nails and feet caused by fungi belonging to the genera Trichophyton, Epidermophyton and Microsporum Antibiotic used in veterinary medicine to treat ringworm in animals Claviceps purpurea Ergotamine Is an ergopeptine and part of the ergot family of alkaloids; It is structurally and biochemically closely related to ergoline. It possesses structural similarity to several neurotransmitters, and has biological activity as a vasoconstrictor It is used medicinally for treatment of acute migraine attacks (sometimes in combination with caffeine) Toxic fungi Amanita muscaria Fungal toxins Alpha-amanitin (deadly: causes liver damage 1–3 days after ingestion) – principal toxin in genus Amanita. Phallotoxin (causes gastrointestinal upset) – also found in poisonous Amanitas Orellanine (deadly: causes kidney failure within 3 weeks after ingestion) – principal toxin in genus Cortinarius. Muscarine (sometimes deadly: can cause respiratory failure) – found in genus Omphalotus. Gyromitrin (deadly: causes neurotoxicity, gastrointestinal upset, and destruction of blood cells) – principal toxin in genus Gyromitra. Coprine (causes illness when consumed with alcohol) – principal toxin in genus Coprinus. Ibotenic acid (causes neurotoxicity) and muscimol (causes CNS depression and hallucinations) – principal toxins in Amanita muscaria, A. pantherina, and A. gemmata. Psilocybin and psilocin (causes CNS arousal and hallucinations) – principal 'toxins' in psilocybin mushrooms, many of which belong to the genus Psilocybe. Arabitol (causes gastrointestinal irritation in some people). Bolesatine a toxin found in Boletus satanas Ergotamine (deadly: affects the vascular system and can lead to loss of limbs and death): An alkaloid found in genus Claviceps (B) Inorganic Sources (Mineral sources): Drugs obtained from inorganic sources have been simply classified into metals and non-metals. Metalloids which show intermediate properties are usually discussed along with metals. The elements either occur in native state or combined state. 1. Metals : Minerals are the main source of metals. Agent Use Magnesium sulphate Purgative Calcium carbonate Astringent Copper sulphate Emetic Ferrous sulphate Haematinic Zinc sulphate Astringent Bismuth subnitrate Antiseptic Lead acetate Local sedative, antiseptic 2. Non-metals : These are also used for various purposes. Agent Use Iodine (Pot. iodide) Expectorant Bromine (Pot. bromide) Sedative Hydrogen peroxide Antiseptic Sulphur Insecticide, disinfectant Carbon (charcoal) Adsorbant Mineral Sources: i. Metallic and Non metallic sources: Iron is used in treatment of iron deficiency anaemia. Mercurial salts are used in Syphilis. Zinc is used as zinc supplement. Zinc oxide paste is used in wounds and in eczema. Iodine is antiseptic. Iodine supplements are also used Selenium is an antioxidant Gold salts are used in the treatment of rheumatoid arthritis. ii. Miscellaneous Sources Fluorine has antiseptic properties. Borax has antiseptic properties as well. Selenium as selenium sulphide is used in anti dandruff shampoos. Petroleum is used in preparation of liquid paraffin. (II) SYNTHETIC SOURCES OF DRUGS Synthetic drugs are prepared in the laboratory with the help of inorganic and organic drugs. Today majority of drugs are obtained synthetically or semi- synthetically. Numerous drugs which were originally obtained from plants are now prepared synthetically. For example, ether and chloroform (Volatile anaesthetics), sulfonamides and quinolones (antimicrobial drugs), paracetamol (analgesic), pentobarbital and thiopental (hypnotic and parenteral anaesthetics), etc. Synthetic/ Semi synthetic Sources i. Synthetic Sources When the nucleus of the drug from natural source as well as its chemical structure is altered, we call it synthetic. Examples include Emetine Bismuth Iodide ii. Semi Synthetic Sources When the nucleus of drug obtained from natural source is retained but the chemical structure is altered, we call it semi-synthetic. Examples include Apomorphine, Diacetyl morphine, Ethinyl Estradiol, Homatropine, Ampicillin and Methyl testosterone. Most of the drugs used nowadays (such as antianxiety drugs, anti convulsant) are synthetic forms Recombinant DNA technology Recombinant DNA technology involves cleavage of DNA by enzyme restriction endonucleases. The desired gene is coupled to rapidly replicating DNA (viral, bacterial or plasmid). The new genetic combination is inserted into the bacterial cultures which allow production of vast amount of genetic material. Advantages Huge amounts of drugs can be produced. Drug can be obtained in pure form. It is less antigenic Disadvantages Well equipped lab is required. Highly trained staff is required. It is a complex and complicated technique The following is the short description of the active constituents of crude drugs. (a) Alkaloid: These are complex, alkaline, nitrogenous compounds mostly obtained from plants and also animals. Their properties are as follows: They are nitrogenous organic compounds. They are alkaline in reaction (so named alkaloids). They combine with acids to form crystalline salts without production of water. They are readily soluble in alcohol but sparingly soluble in water. But their salts are soluble in water. A few of them are liquid, which nearly contain C, H and N only. The solid alkaloids contain oxygen in addition and are colourless crystalline in nature. Most of the alkaloids are closely related to pyridine and some may be prepared synthetically from pyridine bases. They are mostly bitter in taste. In higher concentration they are potent poisons. Their names mostly end with -ine. Examples : Solid alkaloid : Atropine, morphine, quinine, etc. Liquid alkaloid : Arecholine, nicotine, lobeline Semi-synthetic/synthetic : Apomorphine, homatropine. Animal alkaloid : Adrenaline. (b) Glycosides : They are mostly non-nitrogenous bodies mainly occurring in plants. They are non-nitrogenous compounds having sugar attached to non- sugar part by ether linkage. They are neutral in reaction. They mainly contain C, H and O. Some may have in addition N and few S. They do not combine with acids to form salts. They are mostly soluble in alcohol, less soluble in water and insoluble in ether. Some are highly active, while others are practically inert. These are hydrolysed by acids and liberate aglycone (non-sugar part). Their names usually end with -in. Examples : Digitoxin, scillarin, digoxin, etc. (c) Saponins : These are plant glycosides which have distinctive property of frothing. They are a group of non-nitrogenous substances usually glycosides. They are soluble in water and form froth when shaken. On hydrolysis they split up into sugar and aglycone (sapogenin). Toxic saponins are called sapotoxins. Examples : Digitonin, senegin, glycyrrhizin, etc. (d) Resins : These are rosin-like substances which are oxidative products of volatile oils. They are produced by some plants. They are invariably composed of a large number of substances which may be acid, alcohol or ester in chemical composition. They are secretions of plant tissues. They are bitter and amorphous solids. They are insoluble in water, but soluble in alcohol, ether, etc. They are soluble in alkalies forming non-detergent resin soaps. Resins Examples : Resin of Jalap, podophyllin. Oleo-resins : They are natural plant exudates which are semisolid mixtures of resins and volatile oils, e.g. crude turpentine. Gum-resins : They are mixture of resins and gums, e.g. asafoetida. Balsams : They are oleoresins containing benzoic acid or cinnamic acid, e.g. benzoin, balsam of Peru, etc. (e) Tannins: Tannins are non-nitrogenous phenol derivatives characterised by their astringent action on the mucous membrane. They mainly occur in leaves and barks of the plant. They have irritant or astringent action. They react with iron to form blue colouration. They precipitate metallic salts, alkaloids and proteins. Some are glycosides, i.e. occur in combination with sugar. Example : Tannic acid obtained from nut galls. (f) Gums : Gums are secretory products of plants which are used as emulsifying agents for oils and, suspending agents for insoluble substances. They are amorphous, colloidal, complex polysaccharides. They dissolve in water forming viscid adhesive fluid known as mucilage. Examples : Acacia, tragacanth. (g) Oils : Oils are obtained from vegetable, animal and mineral sources. Oils are of 3 types : - Volatile, - fixed and - mineral. Volatile oils : These are also called as essential, ethereal, aromatic or flavouring oils as they are responsible for the aroma and odour of plants and flowers. They are composed of diverse chemical compounds such as alcohols, aldehydes, ketones, esters, sulphur compounds, etc. They are mainly present in the flowering parts of plant, leaves and fruits and give characteristic smell to plants. They are mainly obtained by a process of distillation without being decomposed. They do not form soap with alkalies. Volatile oils They are less soluble in water but more soluble in organic solvents. Alcoholic solutions of these oils are known as essences and are used in perfumery. They do not leave a grease spot on paper. On exposure to air and light, they tend to oxidise and turn rancid. Examples : Liquid volatile oil : Eucalyptus oil, clove oil. Solid volatile oil : Camphor, menthol, thymol. Fixed oils : They are esters of higher fatty acids (oleic, palmitic, stearic acids) and glycerines. They are obtained from fruits, seeds and some other parts of the plants. They are non-volatile and as such cannot be distilled without decomposition, so obtained by process of expression. They are insoluble (immiscible) in water, sparingly soluble in alcohol and freely soluble in ether. They are liquid at ordinary temperature. They leave a permanent grease spot on paper. They turn rancid on heating. They form soap with alkalies. Examples : Vegetable oils : Olive oil, castor oil, mustard oil. Animal oils : Cod liver oil, shark liver oil. Fats : These are also oils containing more of palmitin and stearin making them solid at ordinary temperature, e.g. lard, lanolin, butter. Mineral oils : These are obtained by boring the earth and do not belong to organic class. Some are used in medicinal preparations and contain only C and H, e.g. liquid paraffin. (h) Waxes : They are esters of higher fatty acids and higher monohydric alcohols. They are firmer in consistency and have higher melting points. Ex: Yellow and white bees wax. UNIT-III Classification of crude drugs: - Alphabetical, - Morphological, - Taxonomical and - Chemical classification methods. Crude Drugs They are available in their original form of occurance Organised drugs are the organs of plants, solid, cellular in nature and identified by their microscopical characters. Ex. Cinnamon, Senna Unorganised drugs are the products of plants or animals, solid, semisolid or liquid in nature and are identified by chemical tests basing on the type of chemical constituents present in them Ex. Acacia, Honey, Castor oil Pharmaceutical Aids The substances which are of little or no therapeutic value, but are essentially used in the manufacture or compounding of various pharmaceuticals are known as Pharmaceutical aids or Pharmaceutic necessities They may be obtained from Plants Pectin, Starch Animals Honey, Gelatin, Wool fat Minerals Kaolin, Talc Pharmaceutical Aids They are also classified into Colouring agents : Caramel, Turmeric, Saffron Flavouring agents : Cardamom, lemon oil, Mentha oil Sweetening agents : Licorice, Honey Emulsifying and Suspending agents : Acacia, Agar, Bentonite, Gelatin Ointment bases : Bees wax, Lanolin, wool fat Diluents : Sesame oil, glucose, lactose Vehicles : Olive oil, Arachis oil Disintegrating agents : Starch, Ispagol husk Lubricants :Talc, Cocoa butter CLASSIFICATION OF NATURAL PRODUCTS The most important natural sources of drugs are (higher plants, microbes, animals and marine organisms. Some useful products are obtained from minerals that are both organic and inorganic in nature. To follow the study of the individual drugs, one must adopt some particular sequence of arrangement and this is referred to a system of classification of drugs. A method of classification should be : A)Simple B) Easy to use C) Free from confusion & ambiguities Because of their wide distribution, each arrangement of classification has its own merits and demerits, but for the purpose of this study the drugs are classified in the following different ways: CLASSIFICATION OF NATURAL PRODUCTS (cont.) Alphabetical classification. Morphological classification Taxonomic classification Chemical classification Chemo - taxonomical classification Pharmacological classification 1. Alphabetical Classification Alphabetical classification is the simplest way of classification of any disconnected items. Crude drugs are arranged in alphabetical order of their Latin and English names ( Common names ) or sometimes local names Some of the pharmacopoeias, dictionaries and reference books which classify crude drugs according to this system are as follows : - Indian Pharmacopoeia. - British Pharmacopoeia - British Herbal Pharmacopoeia - United States Pharmacopoeia & National Formulary - British pharmaceutical Codex - European Pharmacopoeia Alphabetical Classification: In this system the crude drugs are arranged in alphabetical order This system is adopted by B.P., B.P.C., U.S.P. and I.P. Whereas in International Pharmacopoeia drugs are arranged according to Latin names. Disadvantages Classification system does not help in Differentiating drugs of Plant, animal or mineral sources. Organized and unorganized drugs cannot be differentiated. 2. Morphological Classification In this system the drugs are arranged according to the morphological or external characters of the plant parts or animal parts i.e. ( which part of the plant is used as a drug e.g. ( leaves, roots, stems, etc. ). The drugs which obtained from the dried parts of the plants & containing cellular tissues are called ( Organized Drugs ) e.g. ( Rhizomes, barks, leaves, fruits, entire plants, hairs,& fibers ). The drugs which are prepared from plants by some intermediate physical processes such as ( incision, drying or extraction with a solvent and not containing any cellular plant tissues are called (unorganized drugs ) such as ( Aloe juice, opium latex, agar, gambir, gelatin, tragacanth, benzoin, honey, beeswax, lemon grass oil etc.). Morphological Classification In this system the crude drugs are classified according to their morphological characters like leaves, barks, seeds, fruits, roots, flowers etc., Advantages: It is more convenient for practical purpose. Even if the chemical content or action of drug is not known the drug can be studied properly. It gives idea about source of drugs It gives idea whether it is organized / unorganized. Useful in identification of adulterants. Morphological Classification Disadvantages: It is difficult to classify unorganized drugs. Chemical composition and pharmacological behaviour of drugs cannot be characterized by this system. Processing of drugs like collection, drying and preparation for market may change their original characters making recognition quite difficult. i.e During collection, drying & packing morphology of drug changes. They are difficult to study. Illustration of Morphological Classification Part of plant Drugs___________________ Leaves Vasaka, Digitalis, Senna, Coca, Datura, Eucalyptus Barks Cinnamon, Cinchona, Cascara Ashoka, Arjuna Flowers Clove, Pyrethrum, Artemisia Seeds Linseed, Mustard Isapgol, Nux-vomica Morphological Classification Fruits Dill, coriander, Bael Colocynth, Gokhru Roots Ipecacuanha, Rauwolfia, Aconite, Gentian Rhizomes Rhubarb, Male fern Turmeric, Ginger Morphological Classification Bulbs Scilla Garlic Corns Colchicum Entire plants Ephedra ,Chirata Ergot , Belladonna Herb Morphological Classification Woods Quassia Sandalwood Hairs & Fibres Cotton Jute Hemp Unorganised Drugs Dried latex Opium Dried juice Aloe Dried extracts Agar, Catechu, Gelatin Gums Tragacanth, Acacia, Guar gum Unorganised Drugs Resins and Resin combinations Colophony Benzoin Asafoetida Basam of Tolu Myrrh Unorganised Drugs Fixed oils Castor oil, Arachis oil Chaulmoogra oil Fats Lard Waxes Wool Fat Bees Wax 2. Morphological Classification (cont.) Organized Drugs : Woods – Quassia, Sandalwood, Red Sandalwood. Leaves – Digitalis, Eucalyptus, Mint, Senna, Spearmint, Squill, Coca, Hyoscyamus, Belladonna, Tea. Barks – Cascara, Cassia, Cinchona, Wild cherry. Flowering parts – Clove, Pyrethrum, Saffron, Santonica, Chamomile. Fruits – Anise, Bitter orange peel, Capsicum, Caraway, Cardamom, Colocynth, Coriander, Cumin, Dill, Fennel, Lemon peel, Senna pod, Star anise, Tamarind. Seeds – Bitter almond, Black Mustard, Cardamom, Colchicum, Linseed, Nux vomica, Psyllium, White mustard. Roots & Rhizomes – Aconite, Colchicum corm, Garlic, Gentian, Ginger, Ginseng, Glycyrrhiza, Podophyllum, Rauwolfia, Rhubarb, Turmeric, Valerian, Squill. Plants & Herbs – Ergot, Ephedra, Yeast, Vinca, Datura. Hair & Fibers- Cotton, Hemp, Jute, Silk, Flax 2. Morphological Classification (cont.) Un - Organized Drugs: Dried latex – Opium, Papain. Dried Juice – Aloe, Kino. Dried extracts – Agar, Black catechu, Pale catechu, Pectin. Waxes – Beeswax, Spermaceti, Carnauba wax. Gums – Acacia, Guar gum, Indian gum, Resins – Asafetida, Benzoic, Colophony, Mastic, Coal tar, Tar, Tolo balsam , Storax, sandarac. Volatile oil – Turpentine, Anise, Coriander, Peppermint, Rosemary, Sandalwood, Cinnamon, Lemon, Caraway, Dill, Clove, Eucalyptus, Nutmeg, Camphor. Fixed oils & Fats – A rachis, Castor, Coconut, Cotton seed, Linseed, Olive, Sesame, Almond, Theobroma, Cod – liver, Halibut liver, Kokum butter. Animal Products – Bees wax, Cod – liver oil, Gelatin, Halibut liver oil, Honey, Shark liver oil, Shellac, Spermaceti wax, Wool fat, Musk, Lactose. Fossil organism & Minerals – Bentonite, Kaolin, Kiesslguhr, Talc. 3. Taxonomical Classification : Taxonomical classification is purely a botanical classification; It is based on principles of natural relationship & evolutionary developments. They are grouped in (Kingdom, Phylum, Order, Family, Genus & Species). As all the entire plants are not used as drugs, parts of plant are used as a drug; for example, Cinnamon bark. This is of no significance from identification point of view to put plants in a taxonomic order. Table (1) give the account of main characters of various taxon that contribute crude drugs while as Table (2) gives the taxonomical classification of some drugs. Taxonomical Classification Purely Botanical classification Crude drugs from plants are classified into Phylum, Order, Family, Genus and Species. Animal drugs classified as fishes, arthropods, mammals etc., Disadvantages It cannot differentiate organized and unorganized drugs. In most of the cases only plant part or product is used so it is of no significance from the point of view of identification. Illustration of Taxonomical Classification Phylum Order Family________ Gymnosperms Gnetales Ephedraceae Angiosperms Canaverales Papaveraceae Dicotyledons Rhamnales Rhamnaceae Angiosperms Lilifore Liliaceae 4- Chemical Classification All plants and animals biosynthesize various chemical compounds like carbohydrates, proteins, fats etc. In addition to these essential chemicals living organisms produce several other chemicals and these chemical constituents possess pharmacological activity. Advantages This classification gives logical reasoning to - biological activities of crude drugs - which are due to chemical constituents. Disadvantages Drugs which contains two or more types of chemical constituents cannot get appropriate placement by this system. 4 - Chemical classification : The crude drugs are divided into different groups according to the chemical nature of their most important constituent. Since the pharmacological activity and therapeutic significance of crude chemical classification of drugs is dependent upon the grouping of drugs with identical constituents. Illustration of Chemical Classification is as follow : 1. Carbohydrates – Carbohydrates are polyhydroxy aldehydes or ketones containing an unbroken chain of carbon atoms. Gums - Acacia, Tragacanth Mucilages – Plantago seed Others - Starch, Honey, Agar, Pectin, Cotton. 2. Glycosides – Glycosides are compounds which upon hydrolysis give rise to one or more sugars ( glycone ) and non – sugar ( aglycone ). Anthraquinone Glycosides – Aloe , Cascara , Rhubarb , Senna Saponins Glycosides –Quillaia , Glycyrrhiza Cyanophore Glycosides – Wild cherry bark Isothiocyanate Glycosides – Mustard Cardiac Glycosides – Digitalis , Strophanthus Bitter Glycosides – Gentian , Calumba , Quassia 4 - Chemical classification (cont.) 3. Tannins – Tannins are complex organic, non – nitrogenous derivatives of polyhydroxy benzoic acids. Ex : Pale catechu, Black catechu, Ashoka bark, Galls, Amla. 4. Volatile Oils – Monoterpenes & Sesquiterpenes obtained from plants. Ex : Cinnamon, Fennel, Dill, Caraway, Coriander, Cardamom, Orange peel, Mint, Clove, Valerian. 5. Lipids – Fixed oils – Castor , Olive , Almond , Shark liver oil. Fats – Theobroma , Lanolin. Waxes – Beeswax. 6. Resins – Complex mixture of compounds like resinols, resin acids, resinotannols, resenes.Ex : Colophony, Podophyllum, Cannabis, Capsicum, Turmeric, Balsam of Tolu and Peru, Myrrh, Ginger. 4 - Chemical classification (cont.) 7. Alkaloids – Nitrogenous substance of plant origin Pyridine and Piperidine – Lobelia, Nicotiana Tropane – Coca, Belladonna, Datura, Stramonium, Hyoscyamus, Henbane. Quinoline - Cinchona Isoquinoline – Opium, Ipecac, Calumba. Indole – Ergot, Rauwolfia. Amines – Ephedra Purine – Tea, Coffee. 8. Protein – Gelatin, Ficin, Papain 9. Vitamins – Yeast 10-Triterpines – Rasna, Colocynth 5- Chemotaxonomical Classification Phytochemical evaluation (the chemical examination of several plants) have established that there is Close link between their Chemical constituents and taxonomical status. Ex. Solanaceae family contains Tropane alkaloids Umbelliferae family contains Volatile oil Pinaceae family contains Oleo-resin 5- Chemotaxonomic Classification: This system of classification relies on the chemical simillarity of taxon i.e. it is based on the existence of relationship between constituents in various plants. There are certain types of chemical constituents that characterize certain classes of plants. This gives birth to entirely new concept of chemotaxonomy that utilizes chemical facts / characters for understanding the taxonomical status, relationships and the evolution of the plants. For example, tropane alkaloids generally occur among the members of Solanaceae thereby, serving as a chemotaxonmic marker. Similarly plant metabolites can serve as the basis of classification of crude drugs. The berberine alkaloid in Berberis and Argemone, Rutin in Rutaceae members, ranunculaceous alkaloids among its members etc are examples It is the latest system of classification and gives more scope for understanding the relationship between chemical constituents , their biosynthesis and their possible action. Classification of Natural Products based on molecular skeleton Classification of Naturally Occurring Compounds According to Number of carbon atoms in the molecule # of Carbon Atoms Carbon Skeleton Possible Groupings 5 C5 Isoprenoids 6 C6 Simple phenols 7 C6 – C1 Phenolic acids 8 C6 – C2 Acetophenones; phenylacetic acid 9 C6 – C3 Cinnamic acid derivatives; phenyl propenes; coumarins, isocoumarins, chromenes 10 C6 – C4 Naphthoquinones C5 – C5 Monoterpenes 13 C6 – C1 – C6 xanthones 14 C6 – C2 – C6 Stilbenes, anthraquinones 15 C6 – C3 – C6 Flavonoids, isoflavonoids, neoflavonoids C5 – C5 – C5 Sesquiterpenoids 18 (C6 – C3) 2 Lignans 20 (C5 – C5) 2 Diterpenes 24 C6 – C3 – C6 – C3 – C6 Complex flavonoids 30 (C6 – C3 – C6) 2 Biflavonoids (C5 – C5) 3 Triterpenoids 40 (C5 – C5) 4 Carotenoids n (C6 – C3) n Lignins (C6 – C1) n Tannins (hydrolysable) (C6 – C3 – C6) n Tannins (condensed) Depends on N- alkaloids Sometimes as glycosides containing heterocyclic ring 6- Pharmacological Classification In this system drugs are grouped together according to the therapeutic activity of their main chemical constituents. 6- Pharmacological Classification : In this system grouping of drug according to their pharmacological action or of most important constituent or their therapeutic use is termed as pharmacological or therapeutic classification of drug. This classification is more relevant and is mostly followed method. Drugs like digitalis, Squill and strophanthus having cardiotonic action are grouped together irrespective of their parts used or phylogenetic relationship or the nature of phytoconstituents they contain. Advantages Even if chemical constituents are not known Drugs can be grouped according to therapeutic utility. Disadvantages Same drug having different actions, may be included in more than one category. Some crude drugs have two different pharmacological actions therefore it is difficult to classify them. Ex: Nux- vomica is CNS stimulant as well as bitter tonic. Cinchona is bitter tonic as well as Antimalarial & Antipyretic. Drugs that have different mechanism of action have to be grouped together. Ex: Castor oil is irritant purgative & Isapgol is bulk purgative but they are placed in one group. No idea whether drugs are organized or unorganized This method does not give any idea of source of drugs. Illustration of Pharmacological Classification Pharmacological Action: Anticancer Vinca Anti Spasmodic Datura, belladonna Anti asthamatics Ephedra Anthelmintic Kurchi Anti amoebic Ipecac Astringents Catechu Anti diabetic Gymnema Cardio tonics Digitalis, squill Carminatives Cinnamon, clove, fennel Expectorant Vasaka Laxatives Senna, Aloes Mydriatic Datura Oxytocic Ergot Quiz The classification method useful for practical purpose in Pharmacognosy a) Taxonomical b) Pharmacological c) Morphological d) Chemical Questions 1. Describe various systems of classification of crude drugs. Give the merits and demerits. 2. Give an account of the different methods of classification of drugs giving their merits and demerits. 3. How the crude drugs are evaluated by organoleptic characters physical methods and biological methods. 4. Define the term crude drug. Mention the various drugs obtained from animals. Cultivation of medicinal plants. ❖Factors influencing cultivation of medicinal plants. ❖Types of soils and fertilizers of common use. ❖Pest management and natural pest control agents. ❖Plant hormones and their applications. ❖Polyploidy, Mutation and hybridization with reference to medicinal plants. ❖Good Agriculture Practices. CULTIVATION OF MEDICINAL PLANTS 1. Factors influencing cultivation of medicinal plants Interest in traditional systems of medicine and, in particular, herbal medicines, has increased substantially in both developed and developing countries over the past three decades. Global and national markets for medicinal herbs have been growing rapidly, and significant economic gains are being realized. Global sales of herbal products totalled an estimated US$ 60 000 million in 2000. As a consequence, the safety and quality of herbal medicines have become increasingly important concerns for health authorities and the public alike. 1. Factors influencing cultivation of medicinal plants (cont) Some reported adverse events following the use of certain herbal medicines have been associated with a variety of possible explanations, including the inadvertent use of the wrong plant species, adulteration with undeclared other medicines and/or potent substances, contamination with undeclared toxic and/or hazardous substances, overdosage, inappropriate use by health-care providers or consumers, and interaction with other medicines, resulting in an adverse drug interaction. Among those attributable to the poor quality of finished products Some clearly result from the use of raw medicinal plant materials that are not of a sufficiently high quality standard. 1. Factors influencing cultivation of medicinal plants (cont) The safety and quality of raw medicinal plant materials and finished products depend on factors that may be classified as intrinsic (genetic) or extrinsic (environment, collection methods, cultivation, harvest, post-harvest processing, transport and storage practices). Inadvertent contamination by microbial or chemical agents during any of the production stages can also lead to deterioration in safety and quality. Medicinal plants collected from the wild population may be contaminated by other species or plant parts through misidentification, accidental contamination or intentional adulteration, all of which may have unsafe consequences. The collection of medicinal plants from wild populations can give rise to additional concerns related to global, regional and/or local over-harvesting, and protection of endangered species 1. Factors influencing cultivation of medicinal plants (cont) The impact of cultivation and collection on the environment and ecological processes, and the welfare of local communities should be considered All intellectual property rights with regard to source materials must be respected. Safety and quality assurance measures are needed to overcome these problems and to ensure a steady, affordable and sustainable supply of medicinal plant materials of good quality Good Agricultural Practices (GAP) have been recognized as an important tool for ensuring the safety and quality of a variety of food commodities 1. Factors influencing cultivation of medicinal plants (cont) Quality Control (QC) for the cultivation and collection of medicinal plants as the raw materials for herbal medicines may be more demanding than that for food production; possibly for this reason, only China, the European Union, and Japan have recently developed guidelines on good agricultural practices for medicinal plants There is need for Good Collection Practices (GCP) for medicinal plants. The following factors are influencing of cultivation: Light Temperature, Atmosphere humidity, Altitude, Rainfall, Soil, Fertilizer, Polyploidy, Mutation, Hybridization, Green house effect 1. Light: Light is the only external source of energy for the continuation of life of the plant. It influences photosynthesis, opening and closing of stomata, plant movements, seed germination, flowering and vegetative growth like tuber formation. Dry sunny weather increases the proportion of glycosides in digitalis and of alkaloids in belladonna. 1. Factors influencing cultivation of medicinal plants (cont) 2. Temperature: Temperature is the major factor influencing the cultivation of the medicinal plant. The sudden decrease in temperature caused the formation of the ice crystals in intercellular spaces of the plant. As a result, water comes out of the cells and ultimately plants die due to drought and desiccation. The ice crystals also causes mechanical injury to the cells. Temperature stimulates the growth of seedlings. Water absorption decreases at low temperatures. The rate of photosynthesis is affected by change in temperature. The rate of respiration increases with increase in temperature. Examples; Cinchona- 58-73°F; Tea- 75-90°F and coffee- 55-70°F 1. Factors influencing cultivation of medicinal plants (cont) 3. Atmosphere humidity: It is present in the form of water vapour. This is called atmospheric humidity. Clouds and fog are the visible forms of humidity. The major sources of water vapour in the atmosphere are evaporation of water from earth surface and transpiration from plants the major effect of humidity on plant life and climate. Evaporation of water, its condensation and precipitation depends upon relative humidity and humidity affects structure, form and transpiration in plants. 4. Altitude: The altitude is the most important factor influencing of cultivation of medicinal plants. The increase the altitude, the temperature and atmospheric pressure decreases while the wind velocity, relative humidity and light intensity increases. Thus, as the climatic conditions change with height, they also produce change in the vegetation pattern. The bitter constituents of Gentiana lutea increase with altitude, whereas the alkaloids of Aconitum nacelles and lobelia inflate and oil content of thyme and peppermint decrease. Pyrethrum gives the best yield and Pyrethrum at high altitude. Examples: Tea- 9500-1500 meters; cinnamon- 300- 1000 meters and saffron- up to 1250 meters. 1. Factors influencing cultivation of medicinal plants (cont) 5. Rainfall: The rainfalls are most important factor influencing of cultivation of medicinal plants. The main source of water for the soil is rain water. Rainfall and snowfall have a large effect on the climate condition. The water from rainfall flows into the rivers and lakes percolates into the soil to form ground water and remaining is evaporated. The minerals in the soil get dissolved in water and are then absorbed by plants. Water influences morphological and physiology of plant. Examples: continuous rain can lead to a loss of water- soluble substance from leaves and root by leaching; this is known to apply to some plants producing glycoside and alkaloids. 1. Factors influencing cultivation of medicinal plants (cont) 6. Soil: Soil is defined as surface layer of the earth, formed by weathering of rocks. The soil is formed as a result of combined action of climate factors like plants and microorganisms. The soil should contain appropriate amounts of nutrients, organic matter and other elements to ensure optimal medicinal plant growth and quality. Optimal soil conditions, including soil type, drainage, moisture retention, fertility and pH, will be dictated by the selected medicinal plant species and/or target medicinal plant part. The soil made of five components: (i) Mineral matter. (ii) Soil air. (iii) Soil water. (iv) Organic matter or humus. (v) Soil organisms ▪ Plants depend on soil for nutrients, water supply and anchorage. Soil influences seed germination, capacity of plant to remain erect, form, vigour and woodiness of the stem, depth of root system, number of flowers on a plant, drought, frost, etc. Classification of soil particles: 1. Clay 2. Loamy. 3. Silt loam 4. Sandy loam 5. Sandy soil. 6. Calcareous soil. a. Clay soil: Clay particle are very small. These fit together very closely and therefore, leave very less pore space. These spaces get filled up with water very easily. Hence, the clay soil becomes quickly waterlogged. Such soil have practically no air, therefore, the plants growing in these soil are not able to absorb water. This soil known as physiologically dry soil, clay soil is plastic and forms a colloid when moist. It cracks and shrinks when conditions are dry the soil rich in nutrient elements and therefore, acts as a negatively charged colloidal system. b. Sandy soil: Sand particles are large sized. These leave large pore spaces which do not have capillary action and therefore, water is not retained by them. Most of the water is quickly drained off and reaches deep into the soil. As a result, roots spread and also reach a great depth. The sandy soil is poor in nutrient elements; it is less fertile and plants growing in this soil have less dry weight. c. Loam soil: The mixture of clay, silt and sand is known as loam. Loam is very useful for growth. It is fertile soil because it contains available nutrient elements in sufficient amounts. It has a high water retention capacity and appropriate amount of soil air is also present. The plants growing in loam are vigorous and have very high weight. d. Sandy loam: The amount of sand particles is more than other types of loam. Silt loam: Silt loam is considered to be the most fertile as it contains more amount of organic substances than others. 7. Fertilizer: The fertilizers are two types: 1. Biological origin fertilizer. 2. Chemical fertilizer Biological origin fertilizer: Soil is generally poor in organic matter and nitrogen. The substances of biological origin used as fertilizer are thus selected if these could provide the elements required. These are two types: (i) Manures: Manure is material, which are mixed with soil. These supply almost all the nutrients required by the crop plants. This results in the increase in crop productivity. Manures are three types: Farmyard manure: This is a mixture of cattle dung and remaining unused parts of straw and plants stalks fed to cattle. Composited manure: This consists of a mixture of rotted or decomposed and useless parts of plants and animals. Green manure: It is a herbaceous crop ploughed under and mixed with the soil while still green to enrich the soil. The plants used as green manure are often quick growing. These add both organic as well as nitrogen to the soil. It is also forms a protective soil cover that checks soil erosion and leaching. Thus, the crop yield increases by 30-50%. (ii) Bio-fertilizer: It can be defined as biologically active products or bacteria, algae and fungi which useful in bringing about soil nutrient enrichment. These mostly include nitrogen fixing microorganisms. Some of the Bio-fertilizer are as follows: (i) Legume- Rhizobium symbiosis (ii) Azolla- Anabaena symbiosis. (iii) Free- living bacteria. (iv) Loose association of nitrogen fixing bacteria. (v) Cyanobacteria (blue green algae). (vi) Mycorrhiza. 1. Ectomycorrhizae. Increase the interface surface between plant root and soil. Mycorrhizae absorb and store nitrogen, phosphorous, potassium and calcium. 2. Endomycorrhizae 2. Chemical fertilizers: (i) Macronutrients: (a) Nitrogen (b) Phosphorous (c) Potassium (d) Calcium (e) Magnesium (f ) Sulphur. (ii) Micronutrients: (a) Iron (b) Magnese (c) Zinc (d) Boron (e) Copper (f) Molybdenum Carbon, oxygen, hydrogen and chorine are provided from water and air. Examples: Urea, Potash 10. Polyploidy: Plants whose cells contain two sets of chromosomes, derived at fertilization from the union of one set from the pollen and one set from the egg cells, are described as diploids and denoted by “2n”. The term polyploidy is applied to plants with more than two sets of chromosomes in the cells; when four sets are present the plants are described as tetraploids and denoted by “4n”. Tetraploidy is induced by treatment with colchicine, which inhibits spindle formation during cell division, so that the divided chromosomes are unable to separate and pass to the daughter cells. The two sets of chromosomes remain in one cell and this develops to give tetraploids plant. Treatment with colchicine may be applied in various ways, but all depend on the effects produced in the meristem. The seeds may be soaked in a dilute solution of colchicine, or the seedlings, the soil around the seedling or the young shoot treated with colchicine solution. Fertile seed and robust, healthy tetraploid plants were obtained, the tetraploid condition being indicated by the increased size of the pollen grains and stomata; chromosome counts in root-tip preparations confirm the tetraploid condition. The average increase in alkaloids content compared with diploid plants of Datura stromonium and Datura tatula was 68%, with a maximum increase of 211.6%. Similar results were obtained with Atropa belladonna and Hyoscyamus niger, the average increase in belladonna being 93%. Increased Alkaloidal content of tetraploids plants has been confirmed for Datura stromonium and Datura tatula. The diploid of Acorus calamus is 2.1% of volatile oil content but they are converted into tetraploid, they produce 6.8% of volatile oil contents. 11. Mutation: Define: Sudden heritable change in the structure of a gene on chromosome or change the chromosome number. Type of mutations: 1. Spontaneous and induced mutations. 2. Recessive and dominant mutations. 3. Somatic and germinal mutations. 4. Forward, back and suppressor mutation. 5. Chromosomal, genomic and point mutations. Mutations can be artificially produced by certain agents called mutagens or mutagenic agent. They are two types: a. Physical mutagens: (i) Ionizing radiations: X-rays, gamma radiation and cosmic rays. (ii) Non-ionizing radiation: U.V. radiation, b. Chemical mutagens: (iii) Alkylating and hydroxylating agents: Nitrogen and sulpher mustard; methyl and ethylsulphonate, ethylethane sulphonates. (iv) Nitrous acid: (v) Acridines: Acridines and proflavins. Ionizing radiation cause breaks in the chromosome. These cells then show abnormal cell divisions. If these include gametes, they may be abnormal and even die prematurely. Non-ionizing radiation like Ultra Violet rays are easily absorbed by purine and pyrimidines. The changed bases are known as photoproducts. U.V. rays cause two changes in pyrimidine to produce pyrimidine hydrate and pyrimidine dimmers. Thymine dimer is a major mutagenic effect of U.V. rays that disturbs DNA double helix and thus DNA replication. Example: Penicillin, as an antibiotic was first obtained from Penicillium. However, the yield was very poor and the preparation was commercially expensive. Since then mutants with higher yield of penicillin have been selected and produced. Penicillium chrysogenum used in the production of penicillin yielded about 100 units of penicillin per ml of culture medium. By single-spore isolation, strains were obtained which yielded up to 250 units per ml of medium, X-ray treatment of this strain gave mutants which produce 500 units per ml and ultraviolet mutants of latter gave strain which produced about 1000 unit per ml. Similarly improvements have been obtained with other antibiotic- producing organism. Mutant strains of Capsicum annum with increasing yields (20-60%) of capsaicin have been isolated from M3 and M4generations originating from seed treated with sodium azide and ethyl methane sulphonate. 12. Hybridization: It is mating or crossing of two genetically dissimilar plants having desired genes or genotypes and bringing them together into one individual called hybrid. The process through which hybrids are produced is called hybridization. Hybridization particularly between homozygous strains, which have been inbred for a number of generations, introduces a degree of heterozygosis with resultant hybrid vigour often manifest in the dimensions and other characteristic of the plants. A hybrid is an organism which results from crossing of two species or varieties differing at least in one set of characters. The following steps are involved in hybridization of plant: 1. Choice of parents: The two parents to be selected, at least one should be as well adopted and proven variety in the area. The other variety should have the characters that are absent in the first chosen variety. 2. Emasculation: Removal of stamens or anthers or killing the pollen grains of a flower without affecting the female reproductive organs is known as emasculation. Emasculation is essential in bisexual flowers. 3. Bagging: Immediately after emasculation, the flowers or inflorescences are enclosed in bags of suitable sizes to prevent random cross- pollination. 4. Pollination: In pollination, mature, fertile and viable pollens are placed on a receptive stigma. The procedure consists of collecting pollens from freshly dehisced anthers and dusting them on the stigmas of emasculated flowers. 5. Raising F1 plants: Pollination is naturally followed by fertilization. It results in the formation of seeds. Mature seeds of F1 generation are harvested dried and stored these seeds are grown to produce F1 hybrid. Hybrids of cinchona yield more amount of quinine. A hybrid developed by crossing Cinchona succirubra with Cinchona ledgering yields a bark, which contains 11.3% of alkaloids. The parent species produced 3.4% and 5.1% of alkaloids, respectively. Pyrethrum hybrids have been used for Pyrethrum production; these hybrids are produced either by crossing two clones assumed to be self- sterile or planting a number of desirable clones together and bulking the seed. The hybridization of plant to increase the Pyrethrin contents 13. Green house effect: Normal conditions sun rays reach the earth and heat is radiated back into space. However, when carbon dioxide concentration increases in the atmosphere, it forms a thick cover and prevents the heat from being re-radiated. Consequently, the atmosphere gets heated and the temperature increases. This is called green house effect. In recent past, amount of carbon dioxide has increased from 290 ppm to 330 ppm due to cutting of forests and excessive burning of fossil fuels. The rate at which the amount of carbon dioxide in the atmosphere is increasing, it is expected to cause rise in global temperature. The global warming by two or three degrees would cause polar ice caps to melt, floods in coastal areas, change in hydrologic cycle and islands would get submerged. The following gases produce green house effect like carbon dioxide, sulphur dioxide, oxide of nitrogen, chlorofluorocarbons, etc. Types of Soils and Fertilizers of Common Use The soil should contain appropriate amounts of nutrients, organic matter and other elements to ensure optimal medicinal plant growth and quality. Optimal soil conditions, including soil type, drainage, moisture retention, fertility and pH, will be dictated by the selected medicinal plant species and/or target medicinal plant part. The use of fertilizers is often indispensable in order to obtain large yields of medicinal plants. It is, however, necessary to ensure that correct types and quantities of fertilizers are used through agricultural research In practice, organic and chemical fertilizers are used. Human excreta must not be used as a fertilizer owing to the potential presence of infectious microorganisms or Types of Soils and Fertilizers of Common Use (cont.) Animal manure should be thoroughly composted to meet safe sanitary standards of acceptable microbial limits and destroyed by the germination capacity of weeds. Any applications of animal manure should be documented. Chemical fertilizers that have been approved by the countries of cultivation and consumption should be used. All fertilizing agents should be applied sparingly and in accordance with the needs of the particular medicinal plant species and supporting capacity of the soil. Fertilizers should be applied in such a manner as to minimize leaching. Growers should implement practices that contribute to soil conservation and minimize erosion, for example, through the creation of streamside buffer zones and the planting of cover crops and "green manure" (crops grown to be ploughed in), such as alfalfa. Pest management and Natural Pest Control The pests: Insects, Rodents , Fungi , Beetles, mammals Types of Pest controls Biological pest control Biological pest control is the control of one through the control and management of natural predators and parasites. For example: mosquitoes are often controlled by putting Bt Bacillus thuringiensis ssp. israelensis, a bacterium that infects and kills mosquito larvae, in local water sources. The treatment has no known negative consequences on the remaining ecology and is safe for humans to drink. The point of biological pest control, or any natural pest control, is to eliminate a pest with minimal harm to the ecological balance of the environment in its present form. Cats against rats Lady bugs feed on aphids and can be introduced to reduce the aphid population on crops Mechanical Pest control Mechanical pest control is the use of hands-on techniques as well as simple equipment, devices, and natural ingredients that provide a protective barrier between plants and insects. For example: weeds can be controlled by being physically removed from the ground. This is referred to as tillage and is one of the oldest methods of weed control Physical pest control Physical pest control is a method of getting rid of insects and small rodents by removing, attacking, setting up barriers that will prevent further destruction of one's plants, or forcing insect infestations to become visual. Putting up Impenetrable screens against pests Elimination of breeding grounds Proper waste management and drainage of still water, eliminates the breeding ground of many pests. Garbage provides food and shelter for many unwanted organisms, as well as an area where still water might collect and be used as a breeding ground by mosquitoes. Communities that have proper garbage collection and disposal, have far less of a problem with rats, cockroaches, mosquitoes, flies and other pests than those that don't. Open air sewers are ample breeding ground for various pests as well. By building and maintaining a proper sewer system, this problem is eliminated. Certain spectrums of LED light can "disrupt insects’ breeding Poisoned bait Poisoned bait is a common method for controlling rat populations, however is not as effective when there are other food sources around, such as garbage. Poisoned meats have been used for centuries for killing off wolves, birds that were seen to threaten crops, and against other creatures. This can be a problem, since a carcass which has been poisoned will kill not only the targeted animal, but also every other animal which feeds on the carcass. Humans have also been killed by coming in contact with poisoned meat, or by eating an animal which had fed on a poisoned carcass. This tool is also used to manage several caterpillars e.g. Spodoptera litura, fruit flies, snails and slugs, crabs etc. Field burning Traditionally, after a sugar cane harvest, the fields are all burned, to kill off any insects or eggs that might be in the fields. Examples of these pests are rodents. Hunting Historically, in some European countries, when stray dogs and cats became too numerous, local populations gathered together to round up all animals that did not appear to have an owner and kill them. In some nations, teams of rat catchers work at chasing rats from the field, and killing them with dogs and simple hand tools. Some communities have in the past employed a bounty system, where a town clerk will pay a set fee for every rat head brought in as proof of a rat killing With the many traps available on the market today one can easily remove mice and rats from homes. One must first know what rodent needs to be removed, one can then decide what type of trap is the best suited to your needs. The snap trap is the most widely used, it utilizes a trigger (sometimes shaped like cheese) to hold bait, and kills the rodent by striking it behind the head with a wire rod or jaw. In some instances you may wish to use glue traps also called glue boards. This type of trap requires the mouse or rat to attempt to cross the trap so the glue can hold the rodent. After a catch is made one can euthanize the rodent and dispose of it trap and all, or some glue boards will release the catch when you pour vegetable oil on them, as the oil reacts with the glue to lose its grip. The last type of trap are live catch traps, this type of trap is typically a repeating style so more than one animal can be caught at a time, they can also be released from this trap in a new location if desired. Pesticides Spraying pesticides by planes, handheld units, or trucks that carry the spraying equipment, is a common method of pest control. Crop dusters commonly fly over farmland and spray pesticides to kill off pests that would threaten the crops. However, some pesticides may cause cancer and other health problems, as well as harming wildlife Space fumigation A project that involves a structure be covered or sealed airtight followed by the introduction of a penetrating, deadly gas at a killing concentration a long period of time (24- 72hrs.). Although expensive, space fumigation targets all life stages of pests Space treatment A long term project involving fogging or misting type applicators. Liquid insecticide is dispersed in the atmosphere within a structure. Treatments do not require the evacuation or airtight sealing of a building, allowing most work within the building to continue but at the cost of the penetrating effects. Contact insecticides are generally used, minimizing the long lasting residual effects. Sterilization Laboratory s