History of Pharmacognosy

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Chapter: Pharmacognosy and Phytochemistry : History, Definition and Scope of Pharmacognosy

In the early period, primitive man went in search of food and ate at random, plants or their parts like tubers, fruits, leaves, etc.

History of Pharmacognosy

HISTORY OF PHARMACOGNOSY

 

In the early period, primitive man went in search of food and ate at random, plants or their parts like tubers, fruits, leaves, etc. As no harmful effects were observed he con-sidered them as edible materials and used them as food. If he observed other effects by their eating they were consid-ered inedible, and according to the actions he used them in treating symptoms or diseases. If it caused diarrhoea it was used as purgative, if vomitting it was used as memtic and if it was found poisonous and death was caused, he used it as arrow poison. The knowledge was empirical and was obtained by trial and error. He used drugs as such or as their infusions and decoctions. The results were passed on from one generation to the other, and new knowledge was added in the same way.

 

Ancient China

 

Chinese pharmacy, according to legend, stems from Shen Nung (about 2700 B.C.), emperor who sought out and investigated the medicinal value of several hundred herbs. He reputed to have tested many of them on himself, and to have written the first Pen T-Sao, or Native Herbal, recording 365 drugs. These were subdivided as follows: 120 emperor herbs of high, food grade quality which are non-toxic and can be taken in large quantities to maintain health over a long period of time, 120 minister herbs, some mildly toxic and some not, having stronger therapeutic action to heal diseases and finally 125 servant herbs that having specific action to treat disease and eliminate stagnation. Most of those in the last group, being toxic, are not intended to be used daily over a prolonged period of weeks and months. Shen Nung conceivably examined many herbs, barks and roots brought in from the fields, swamps and woods that are still recognized in pharmacy (podophyllum, rhubarb, ginseng, stramonium, cinnamon bark and ephedra).

 

Inscriptions on oracle bones from the Shang Dynasty (1766–1122 B.C.), discovered in Honan Province, have pro-vided a record of illness, medicines and medical treatment. Furthermore, a number of medical treatises on silk banners and bamboo slips were excavated from the tomb number three at Ma-Huang-Tui in Changsha, Hunan Province. These were copied from books some time between the Chin and Han periods (300 B.C.–A.D. 3) and constitute the earliest medical treatises existing in China.

 

The most important clinical manual of traditional Chinese medicine is the Shang Hang Lun (Treatise on the Treatment of Acute Diseases Caused by Cold) written by Chang Chung-Ching (142–220). The fame and reputation of the Shang Han Lun as well as its companion book, Chin Kuei YaoLueh (Prescriptions from the Golden Chamber), is the historical origin of the most important classical herbal formulas that have become the basis of Chinese and Japanese-Chinese herbalism (called ‘Kampo’).

 

With the interest in alchemy came the development of pharmaceutical science and the creation of a number of books including Tao Hong Jing’s (456–536) compilation of the Pen T’sao Jing Ji Zhu (Commentaries on the Herbal Classic) based on the Shen Nong Pen T’sao Jing, in 492. In that book 730 herbs were described and classified in six categories: (1) stone (minerals), (2) grasses and trees, (3) insects and animals, (4) fruits and vegetables, (5) grains and (6) named but unused. During the Sui dynasty (589–618) the study of herbal medicine blossomed with the creation of specialized books on plants and herbal medicine. Some of these set forth the method for the gathering of herbs in the wild as well as their cultivation. Over 20 herbals were chronicled in the Sui Shu JingJi Zhi (Bibliography of the History of Sui). These include the books Zhong Zhi Yue Fa (How to Cultivate Herbs) and the Ru Lin Cat Yue Fa (How to Collect Herbs in the Forest).

 

From the Sung Dynasty (960–1276) the establishment of pharmaceutical system has been a standard practice throughout the country. Before the ingredients of Chinese medicine can be used to produce pharmaceuticals, they must undergo a preparation process, e.g. baking, simmer-ing or roasting. The preparation differs according to the needs for the treatment of the disease. Preparation methods, production methods and technology have constantly been improved over time.

 

In 1552, during the later Ming Dynasty, Li Shi Zhen (1518–1593) began work on the monumental Pen T’sao Kan Mu (Herbal with Commentary). After 27 years and three revisions, the Pen T’sao Kan Mu was completed in 1578. The book lists 1892 drugs, 376 described for the first time with 1160 drawings. It also lists more than 11,000 prescriptions.

 

Ancient Egypt

 

The most complete medical documents existing are the Ebers Papyrus (1550 B.C.), a collection of 800 prescriptions, mentioning 700 drugs and theEdwin Smith Papyrus (1600 B.C.), which contains surgical instructions and formulas for cosmetics. The Kahun Medical Papyrus is the oldest—it comes from 1900 B.C. and deals with the health of women, including birthing instructions.

 

However, it is believed that the Smith Papyrus was copied by a scribe from an older document that may have dated back as far as 3000 B.C.  


 

Commonly used herbs included: senna, honey, thyme, juniper, cumin, (all for digestion); pomegranate root, henbane (for worms) as well as flax, oakgall, pine-tar, manna, bayberry, ammi, alkanet, aloe, caraway, cedar, coriander, cyperus, elderberry, fennel, garlic, wild lettuce, nasturtium, onion, peppermint, papyrus, poppy-plant, saffron, watermelon, wheat and zizyphus-lotus. Myrrh, turpentine and acacia gum were also used.

 

Ancient India

 

In India knowledge of medicinal plants is very old, and medicinal properties of plants are described in Rigveda and in Atharvaveda (3500–1500 B.C.) from which Ayurveda has developed. The basic medicinal texts in this world region— The Ayurvedic writings—can be divided in three main ones (Charaka Samhita, Susruta Samhita, Astanga Hrdayam Samhita) and three minor ones (Sarngadhara Samhita, Bhava Prakasa Samhita, Madhava Nidanam Samhita). Ayurveda is the term for the traditional medicine of ancient India. Ayur means life and veda means the study of which is the origin of the term. The oldest writing—Charaka Samhita—is believed to date back six to seven centuries before Christ. It is assumed to be the most important ancient authoritative writing on Ayurveda. The Susruta Samhita is thought to have arisen about the same time period as the Charaka Samhita, but slightly after it Astanga Hrdayam and the Astanga Sangraha have been dated about the same time and are thought to date after theCharaka and Susruta Samhitas. Most of mentioned medicines origin from plants and animals, e.g. ricinus, pepper, lilly, valerian, etc.

 

Ancient Greece and Rome

 

Greek scientists contributed much to the knowledge of natural history. Hippocrates (460–370 B.C.) is referred to as father of medicine and is remembered for his famous oath which is even now administered to doctors. Aristotle (384–322 B.C.), a student of Plato was a philosopher and is known for his writing on animal kingdom which is consid-ered authoritative even in twentieth century. Theophrastus (370–287 B.C.), a student of Aristotle, wrote about plant kingdom. Dioscorides, a physician who lived in the first century A.D., described medicinal plants, some of which like belladonna, ergot, opium, colchicum are used even today. Pliny wrote 37 volumes of natural history and Galen (131–A.D. 200) devised methods of preparations of plant and animal drugs, known as ‘galenicals’ in his honour.

 


Pharmacy separated from medicine and materia medica, the science of material medicines, describing collection, preparation and compounding, emerged.

Even upto the beginning of twentieth century, pharma-cognosy was more of a descriptive subject akin mainly to botanical science, and it consisted of identification of drugs both in entire and powdered conditions and concerned with their history, commerce, collection, preparation and storage.

 

The development of modern pharmacognosy took place later during the period 1934–1960 by simultaneous appli-cation of disciplines like organic chemistry, biochemistry, biosynthesis, pharmacology and modern methods and techniques of analytic chemistry, including paper, thin layer, and gas chromatography and spectrophotometry

 

The substances from the plants were isolated, their structures elucidated and pharmacological active constitu-ents studied. The development was mainly due to the following four events:

 

1.           Isolation of penicillin in 1928 by William Fleming and large-scale production in 1941 by Florey and Chain.

2.           Isolation of resperpine from rauwolfia roots and con-firming its hypotensive and tranquilizing properties.

3.           Isolation of vinca alkaloids, especially vincristine and vinblasting. Vincristine was found useful in the treat-ment of leukaemia. These alkaloids also have anticancer properties.

4.           Steroid hormones like progesterone were isolated by partial synthesis from diosgenin and other steroid saponins by Marker’s method. Cortisone and hydro-cortisone are obtained from progesterone by chemical and microbial reaction.

 

This period can also be termed antibiotic age, as besides pencillin, active antibiotics like streptomycin, chloram-phenicol, tetracycline and several hundred antibiotics have been isolated and studied extensively.

 

Some of the important aspects of the natural products that led to the modern development of drugs and phar-maceuticals are as follows:

 

Isolation of phytochemicals

 

Strong acting substances such as glycosides of digitalis and scilla, alkaloids of hyoscyamus and belladonna, ergot, rauwolfia, morphine and other alkaloids of opium were isolated and their clinical uses studied.

 

Structure activity relationship

 

Tubocurarine and toxiferine from curare have muscle relax-ant properties because of quaternary ammonium groups. The hypotensive and tranquillizing actions of reserpine are attributed to the trimethoxy benzoic acid moiety which is considered essential. Mescaline and psilocybine have psy-chocative properties. Presence of a lactone ring is essential for the action of cardiac glycosides. Likewise anthraquinone glycosides cannot have their action without satisfying the positions at C3, C1, C8, C9 and C10.

 

Drugs obtained by partial synthesis of natural products

 

Oxytocic activity of methyl ergometrine is more than that of ergometrine. In ergotamine, by 9:10 hydrogenation, oxytocic activity is suppressed and spasmolytic activity increases. We have already referred to the preparation of steroid hormones from diosgenin by acetolysis and oxi-dation and further preparation of cortisone by microbial reactions.

 

Steroid hormones and their semisynthetic analogues represent a multimillion dollar industry in the United States.

 

Natural products as models for synthesis of new drugs

 

Morphine is the model of a large group of potent analgesics, cocaine for local anaesthetics, atropine for certain spasmo-lytics, dicoumarol for anticoagulants and salicin for salicylic acid derivatives. Without model substances from plants a large number of synthetics would have been missed.

 

Drugs of direct therapeutic uses

 

Among the natural constituents, which even now cannot be replaced, are important groups of antibiotics, steroids, ergot alkaloids and certain antitumour substances. Further, drugs as digitoxin, strophanthus glycosides, morphine, atropine and several others are known since long and have survived their later day synthetic analogues.

 

Biosynthetic pathways

 

Biosynthetic pathways are of primary and secondary metab-olites. Some of the important pathways are Calvin’s cycle of photosynthesis, shikimic acid pathway of aromatic com-pounds, acetate hypothesis for anthracene glycosides and isoprenoid hypothesis for terpenes and steroids via acetate-mevalonic acid-isopentyl pyrophosphate and squalene.

 

Progress from 1960 onwards

 

During this period only a few active constituents mainly antibiotics, hormones and antitumour drugs were isolated or new possibilities for their production were found. From 6-amino penicillanic acid, which has very little antibiotic action of its own, important broad-spectrum semisyn-thetic penicillins like ampenicillin and amoxicillin were developed.

 

From ergocryptine, an alkaloid of ergot, bromocryptine has been synthesized. Bromocryptine is a prolactin inhibitor and also has activity in Parkinson’s disease and in cancer. By applications of several disciplines, pharmacognosy from a descriptive subject has again developed into an integral and important disciplines of pharmaceutical sciences.

 

Technical products

 

Natural products, besides being used as drugs and thera-peutic aids, are used in a number of other industries as beverages, condiments, spices, in confectioneries and as technical products.

 

The coffee beans and tea leaves besides being the source of caffein are used as popular beverages. Ginger and win-tergreen oil are used less pharmaceutically but are more used in preparation of soft drinks. Mustard seed and clove are used in spice and in condiment industry. Cinnamon oil and peppermint oil besides being used as carminatives are used as flavouring agents in candies and chewing gum. Colophony resin, turpentine oil, linseed oil, acacia, pectin, and numerous other natural products are used widely in other industries and are called technical products.

 

Pharmaceuticals aids

 

Some of the natural products obtained from plants and animals are used as pharmaceutical aids. Thus gums like acacia and tragacanth are used as binding, suspending and emulsifying agents. Guar gum is used as a thickening agent and as a binder and a disintegrating agent in the manufacturing of tablets. Sterculia and tragacanth because of their swelling property are used as bulk laxative drugs. Mucilage-containing drugs like ishabgul and linseed are used as demulcents or as soothing agents and as bulk laxatives. Starch is used as a disintegrating agent in the manufacture of tablets and because of its demulcent and absorbent properties it’s used in dusting powders. Sodium alginate is used as an establishing, thickening, emulsifying deflocculating, gelling and filming agent. Carbohydrate-containing drugs like glucose, sucrose and honey are used as sweetening agents and as laxative by osmosis.

 

Agar, in addition to being used as a laxative by osmosis, is also used as an emulsifying agent and in culture media in microbiology. Saponins and sponin-containing drugs are used as detergents, emulsifying and frothing agents and as fire extinguishers. Tincture quillaia is used in preparation of coal tar emulsions. Saponins are toxic and their internal use requires great care, and in some countries their internal use as frothing agents is restricted. Glycyrrhiza is used as sweetening agent for masking the taste of bitter and salty preparations.

 

Fixed oils and fats are used as emollients and as oint-ment bases and vehicles for other drugs. Volatile oils are used as flavouring agents.

 

Gelatin is used in coating of pills and tablets and in preparation of suppositories, as culture media in microbiol-ogy and in preparation of artificial blood plasma. Animal fats like lard and suet are used as ointment bases. Beeswax is used as ointment base and thickening agent in oint-ments. Wool fat and wool alcohols are used as absorbable ointment bases.

 

Thus, from the above description it can be seen that many of the natural products have applications as phar-maceutical aids.

 

Discovery of new medicines from plants— nutraceutical use versus drug development

 

Little work was carried out by the pharmaceutical indus-try during 1950–1980s; however, during the 1980–1990s, massive growth has occurred. This has resulted in new developments in the area of combinatorial chemistry, new advances in the analysis and assaying of plant materials and a heightened awareness of the potential plant materials as drug leads by conservationists. New plant drug develop-ment programmes are traditionally undertaken by either random screening or an ethnobotanical approach, a method based on the historical medicinal/food use of the plant. One reason why there has been resurgence in this area is that conservationists especially in the United States have argued that by finding new drug leads from the rainfor-est, the value of the rainforests to society is proven, and that this would prevent these areas being cut down for unsustainable timber use. However, tropical forests have produced only 47 major pharmaceutical drugs of world-wide importance. It is estimated that a lot more, say about 300 potential drugs of major importance may need to be discovered. These new drugs would be worth $147 billion. It is thought that 125,000 flowering plant species are of pharmacological relevance in the tropical forests. It takes 50,000 to 100,000 screening tests to discover one profitable drug. Even in developed countries there is a huge potential for the development of nutraceuticals and pharmaceuticals from herbal materials. For example the UK herbal materia medica contains around 300 species, whereas the Chinese herbal materia medica contains around 7,000 species. One can imagine what lies in store in the flora-rich India!


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