Contribution of Indian Traditional and Holistic Medicine to New Drug Development N.K. Sachan University Institute of Pharmacy, Chhatrapati Shahu Ji Maharaj University Kanpur–208024 (U.P.) Email:
[email protected]
Abstract: In search for new drugs, traditional knowledge or ‘local knowledge' provides a pointer. The discovery development of a new drug is a tedious and multibillion dollar process. Several approaches have been devised to find out some new pharmacophore, chemical moiety with potential medicinal value, by synthetic chemistry or by drug design. The herbs having claimed therapeutic value can be subjected to pharmacological screening and subsequent chemical profiling if found successful. This may sought a new source of inspiration with the research started on plant-based drugs in new millennium for pharmaceutical world and serve as a kind of sort-cut in realization of drug discovery and development process. The interest of Pharmaceutical industries to screen natural product extracts for new biologically active compounds is increasing due to the high through-put screening methods. For this our huge biodiversity can be explored effectively to find out lead consisting of a large number of chemical structures with potent therapeutic activity for the treatment of deadly ailments. "In the great teaching of the Vedas, there is no touch of sectarianism. It is of all ages, climes and nationalities and is the royal road for the attainment of the Great Knowledge." : - Thoreau American Thinker INTRODUCTION: Since the time immemorial, the man has been in search of such substances that could keep them healthy or make them to get rid of diseases - Called Drugs/Pharmaceuticals. The medicinal substances were obtained from several sources identified in due course of time including minerals, plant sources, synthetic chemicals, biological sources (insulin, androgens) and more recently through biotechnological methods. Globalization, urbanization, an aging population, and rising rates of chronic diseases are creating new health challenges throughout the world with rising demand for the newer drugs to treat new diseases and for those the existing medicines has become useless being accorded as resistant. The herbs having claimed therapeutic value in traditional /folklore system of medicine can be subjected to pharmacological screening and subsequent chemical profiling if found successful. This may sought a new source of inspiration with the research started on plant-based drugs as a clue or short-cut of much rigorous and in-depth multiple pharmacological and phytochemical screening. Today the pharmaceutical industry is a powerhouse performer; it is the notable sign of globalization and capitalism that there is high degree of competition of in terms of money and time in the field of drugs and pharmaceutical research. The country is going through an arduous process of creating a niche market in the world of alternative medicines; the ongoing joint research programmes between the Council of Scientific and Industrial Research (CSIR) and various high profile institutions in the field of alternative medicines, especially Ayurveda and Unani, are all focused towards the
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development and commercialisation of new bioactive compounds from plant sources. How different is your approach, termed as "positivism", when compared to these efforts? Let us first discuss about the Western model of drug development that we are trying to adopt in our scientific and research institutions engaged in new drug development from traditional systems of medicine. Here we are attempting to discover and develop a new therapeutic agent from a known traditional prescription by spending crores of rupees just to ensure its international acceptability. This process takes much time (approximately 12 years) and cannot be completed without external funding either from the government of from the private sector. The process also requires input from several disciplines including pharmacology, analytical sciences, information technology in computing, patent law marketing etc. The whole process takes within the framework of guidelines formulated by regulatory bodies of the government. Is it essential? Or in other words, should we end up with this instead of beginning with all these protocols? Trying to find an answer to this by realizing the Indian situations, it is easy to reach at a conclusion that we need to device our own research programmes, tailor made to suit our needs. All over the world, clinician is understandably interested mainly in the effects of a drug on man. However, technical, legal and ethical considerations make it mandatory for new drug to undergo pharmacological evaluations in animals and later on human beings. The scientific method called ''positivism'' gains significance in this context. Instead of beginning with theory, hypothesis, observation and then medicine, it begins with observation and then based on the records goes on to the hypothesis, which later can be translated into a theory which suits the Western markets. INPUT INTO R&D THROUGH ETHNOPHARMACOLOGY AND TRADITIONAL MEDICINE: Although it has a long history, traditional medicine has become a globalized phenomenon recently, with a flourishing market for its products and practices. It is emphasized that traditional medicine was a field where the knowledge and know-how of ancient cultural practices of our country was enormous and it could serve a source of hope for value added botanicals and new drug development. It is therefore a field where industrialized countries can gain a lot from the experiences of traditional holistic healing practices. Numerous drugs have entered the international pharmacopoeia via the study of ethnopharmacology and traditional medicine. Traditional medical traditions can offer a more holistic approach to drug design and myriad possible targets for scientific analysis. Powerful new technologies such as automated separation techniques, high-throughput screening and combinatorial chemistry are revolutionizing drug discovery. Traditional knowledge can serve as powerful search engine, which will greatly facilitate intentional, focused and safe natural product drug discovery and help to rediscover the drug discovery process. By looking at the historical trends in drug and medical developments, it is possible to understand how current drug development will benefit from this partnership. Despite the small number of species sources explored yet, drugs derived from plants are of immense importance in terms of numbers of patients treated. It is reported that 25% of all prescriptions dispensed from community pharmacies in the USA between 1959 and 1973 contained one or more ingredients derived from higher plants. A more recent study, of the top 150 proprietary drugs used in the USA in 1993, found that 57% of all prescriptions contained at least one major active compound currently or once derived from (or patterned after) compounds derived from biological diversity. Ayurvedic Indian and traditional Chinese systems are living great traditions. These traditions have relatively organized database, and more exhaustive description of botanical material that is available and can be tested using modern scientific methods. Both systems of medicine thus have an important role in bioprospecting of new medicines. Good botanical practices which can improve the quality control procedures of monitoring impurities, heavy metals and other toxins in the raw material can make the ethnopharmacology research more meaning full. Drug Discovery in current scenario has become unproductive to the point where the economic future of the industry is questionable. To push into the future, the R&D thrust in the pharmaceutical sector
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needs to be focused on development of new drugs, innovative processes for known drugs and development of plant-based drugs through investigation of leads from the traditional systems of medicine. Traditional medicine can provide novel inputs into the drug development process. Yet, bioprospecting - the search for economically valuable natural resources - by pharmaceutical companies, or on their behalf, has not been conspicuously successful in recent years. The R&D thrust in the pharmaceutical sector is focused on development of new drugs, innovative/indigenous processes for known drugs and development of plant based drugs through investigation of leads from the traditional systems of medicine. In addition, many nutraceuticals are being consumed from unregulated markets for their perceived benefits in health care and improvement of quality of life. Natural pharmaceuticals, nutraceuticals and cosmeceuticals are of great importance as a reservoir of chemical diversity aimed at new drug discovery and can be explored as potential antimicrobial, cardiovascular, immunosuppressive, and anticancer drugs. Around 80% of all such products are of plant origin; their sales exceeded $ 65 billion in 2003. Examples of plant products and derivatives used by the pharmaceutical industry include Paclitaxel, Vincristine, Vinblastine, Artemisinin, Camptothecin, Podophyllotoxin and such. Natural products including plants, animals and minerals have been the basis of treatment of human diseases. Modern medicine or allopathy has gradually developed over the years of scientific and observational efforts of scientists -- however, the basis of its development remains in the roots of traditional medicine and therapies. The history of medicine includes many ludicrous therapies. Nevertheless, the ancient wisdom has been the basis of modern medicine and will remain as one important source of future medicine and therapeutics. Even during the early part of this century, plants were a vital source of raw material for medicines. The future of natural product drug discovery will be more holistic, personalized and involve wise use of ancient and modern therapeutic skills in complementary manner so that maximum benefits can be given to patients and the community. A large numbers of molecules have come out of Ayurvedic experiential base include Rauwolfia alkaloids for hypertension, Psoralens in Vitiligo, Holarrhena alkaloids in Amoebiasis, Guggulsterons as hypolipidemic agents, Mucuna pruriens for Parkinson’s disease, Piperidines as bioavailability enhancers, Baccosides in mental retention, Picrosides in hepatic protection, Phyllanthins as antivirals, Curcumines in inflammation, Withanolides, and many other steroidal lactones and glycosides as immunomodulators. The age of the blockbuster drug seems over or at least in its last days. The data from a study done by DiMasi and Paquette of Tufts University, suggest that entry barriers have fallen over time for new drug introductions. The increased competitiveness of the pharmaceutical marketplace was likely fueled by changes over time on both the supply and demand sides. The development histories of entrants to new drug classes suggest that development races better characterize new drug development than does a model of post hoc imitation. Thus, the usual distinctions drawn between breakthrough and ‘me-too’ drugs may not be very meaningful. The pharmaceutical industry has not been as innovative as it claims to be and the regulatory processes are adding more risk and years for the pharmaceutical companies and it is predicated that worst is yet to come. Most of the big pharmaceutical manufacturers spend more on marketing than on research and development. Drug companies actively research for new ways to interact with known receptors and seek out new receptors. But the development road is long, stony, and expensive, as seen in many cases of post approval or marketing withdrawal cases such as a new anticoagulant Ximelagatran of Astra Zeneca or Cox II inhibitor Vioxx of Pfizer. Such failures are really becoming nightmares of pharmaceutical companies who are now looking for innovative approaches to drug discovery. There are common approaches to drug discovery including Chemical Biology Approach, Serendipity and Synthetic, Combinatorial, Genomics Approaches. However, the innovative approaches based on TM that are evolving to reduce major bottleneck and to reduce cost and development time, include Ethnopharmacology Approach, Reverse Pharmacology Approach, Systems Biology Approach and Personalized Approach. Various institutions, including the Indian Council of Medical Research (ICMR) and Council for Scientific and Industrial Research (CSIR) in India, are taking another tack, exploring alternative paths to modern pharmaceutical research presented by traditional medicine - paths that could be cheaper, faster and more effective. One such strategy involves a
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process known as reverse pharmacology, which begins with a useful natural product and works backward, as it were, to identify its active ingredients. CSIR has just concluded series of clinical trials on herbal products of medicinal value generated through reverse pharmacology, with several public and private partners. In looking to the future, it is important to consider the relative potential of these approaches to generating cost-effective, safe medical products.
In short, for several reasons, the modern drug discovery processes have started revisiting traditional knowledge and ethnopharcacology to reduce the typical innovation deficit faced today that would help reaching to the top in Sciences especially for developing counties like India. Traditional knowledge and experiential database can provide new functional leads to reduce time, money and toxicity- the three main hurdles in the drug development. These records are particularly valuable since effectively these medicines have been tested for thousands years on people. The Indian CSIR is playing an important role through public-private profiting partnerships in R&D in a very professional manner and has received due appreciation from the corporate, scientific and governmental sectors and its program known as New Millennium Indian Technology Leadership Initiative (NMITLI). In this program of Government of India number of industry partners such as Nicholas Piramal, Lupin, Zandu, Dabur, Dhootpapeshwar, Natural
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Remedies, are part of the project. A review of some exemplary evidence-based researches and approaches has now resulted in wider acceptance of Ayurvedic medicines. One of the bioenhancers developed by RRL is Piperine, which has been studied in detail with anti-TB drugs. With Ayurveda, the normal drug discovery course of ‘Laboratory to Clinics’ actually becomes from ‘Clinics to Laboratories’— a true Reverse Pharmacology Approach. Globally, there is a positive trend towards holistic health, integrative sciences, systems biology approaches in drug discovery and therapeutics that has remained one
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of the unique features of Ayurveda. A golden triangle consisting of Ayurveda-Modern medicine- Modern Science will converge to form a real discovery engine that can result in newer, safer, cheaper and effective therapies. It will be in the interest of pharmaceutical companies, researchers and ultimately the global community to respect the traditions and build on their knowledge and experiential wisdom. Most important fact is Traditions do not mean just drugs or medicine; they are based on philosophical and experiencial principles and practices. An ambitious innovative project to study some of the important basic principles and practices of Ayurveda using most advanced tools of science has been conceived under the name ‘Science Initiatives in Ayurveda’. This program is being supported by the Principal Scientific Advisor’s Office, Government of India and involves premeum national institutes.
ETHANOBOTANICAL DRUG DEVELOPMENT: PLANT DERIVED DRUG MOLECULES AND PHARMACEUTICAL POTENTIALS: Plants have proved invaluable and inexpensive source of “feedstock” molecules that can be readily transformed into drugs. Recently a rejuvenation effort for drug discovery process rom natural products have been undertaken by the Council of Scientific and Industrial Research (CSIR) Govt. of India in the shape of coordinated programme involving 19 CSIR laboratories under its hub and other R&D institutions in the field of traditional medicine along with few academic departments of the universities in India. This programme
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launched in 1996 targeted at the discovery of new bioactive molecules from natural sources. Golden Triangle Partnership (GTP) has been introduced recently as a combined effort by three major government of india institutes viz. Dept. of AYUSH, ICMR and CSIR for the validation of traditional Ayurvedic drugs and development of new drugs.a report suggests that around 38 Ayurvedic formulations have been attempted for 8 disease conditions and out of these 20 formulations have been submitted to CSIR for preclinical studies under GTP. Most of the compounds from Indian plants are being isolated and screened abroad as it is evident from the number of publications of Indian medicinal plants originating from the west. Under such circumstances, integration of traditional and holistic medicinal knowledge obtained from Indian system of medicine as heritage can make this prospect a realistic approach and can help to protect our knowledge heritage. The CDRI evaluated approximately 2,000 plant species for several biologic activities, including antibacterial, antidiabetic, antifertility, antifungal, antihypercholesteremic, anti-inflammatory, antitumor, cardiovascular, central nervous-system depressant,cytotoxicity, diuretic, and others. To date no biologically active drugs for human use have arisen from that program, even though a large number of known and novel bioactive compounds were isolated from the active plants. The input of traditional knowledge regarding medicinal importance of certain plants works as a shortcut and hasten the process of screening simultaneously this also reduce the cost of drug development process from plants. Because of the huge cost involvement in isolation and purification of plant constituents, there are only a few industrial players in market undertaking the drug discovery from plants and many times this perspective remains as an academic exercise rather than full fledged programme. Natural products besides being source of leads for a number of compounds with therapeutic importance also play an important role in the industrial drug synthesis. This is because of the presence of a wide chemical diversity in the plant based natural products which enables the industrial synthetic chemists to have several possible starting materials for several stereospecific reactions. For example, Oseltamivir (Tamiflue) which proved to be an effective drug against Swine flue caused by H1N1 virus. In synthesizing this drug shikimic acid is used as starting material which is obtained from the chinese star anise. A recent study reveals that this compound is present in high yield in Indian plants such as Calophyllum apetalum (4.10% shikimic acid by dry weight) and Araucaria excels (5.02% shikimic acid by dry weight) which can be used as an alternative source of shikimic acid. Natural products also act as bioavailability enhancers in many cases by initiating drug metabolizing enzymes eg. Piperine from Piper spp. Stavioside is used as potent sweetner obtained from Stevia rebaudiana which is a glycoside 300 times more sweet than ordinary sugar. Literature and Ethano-medicinal Information: Ethnomedical information can be acquired from various sources such as books on medical botany and herbals; review articles (usually involving surveys of medicinal plants by geographic region or ethnicculture); notes placed on voucher herbarium specimens by the botanist at the time of collection; field work; and computer databases, e.g., NAPRALERT, TKDL and USDA–Duke etc. Herbalism, folklore, and shamanism can also play an important role in the procurement of potential etheno -medicinal literature. These centers on an apprenticeship system of information passed to the next generation through a shaman, curandero, traditional healer, or herbalist. The plants that are used are often kept secret by the practitioner, so little information about them is recorded; thus there is less dependence on scientific evidence as in systems of traditional medicine that can be subject to scrutiny. The shaman or herbalist combines the roles of pharmacist and medical doctor with the cultural/spiritual/religious beliefs of a region or people, which are often regarded as magic or mysticism. Follow-up of biologic activity reports showed that the plant extracts had interesting biologic activity, but the extracts were not studied for their active principles. The literature from the 1930s through the 1970s contains these types of reports. Several types of ethnomedical information are available towards Follow-up of ethnomedical (traditional medicine) uses of plants involves Ayurveda, Unani, Kampo, and traditional Chinese medicine which have flourished as systems of medicine in use for thousands of years. Their individual arrangements all
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emphasize education based on an established, frequently revised body of written knowledge and theory. These systems are still in place today because of their organizational strengths, and they focus primarily on multicomponent mixtures. Adverse effects from those widely used plants are not well documented in the literature, and efficacy of these plants and plant mixtures is more difficult to assess by Western scientific methods. Table 1: Plant Derived Drugs, their Clinical Use and Source S. No
Common name
Biological name and family
Part used
Active constituent
Therapeutic Indications
Arnica montana (Compositae)
Flower
Panax ginseng (Araliaceae)
Root
Flavonoids, arnifolin Arnidiol, faradiol, helenalin, & epoxy helenalin, arnicin. Ginsenosides, panaxosides, Chikusetsusaponin
Treatment of chronic rheumatism, spinal paralysis, amourosis, hypolipidemic Aphrodisiac, Thyroid& adrenal dysfunction, anaemia.
Root and stem Tuberou s root
Withaferin, somnine, somniferine, , sitoindosides Shatavarins(i-iv),
Bulb
Allin, volatile oils polysulphides,
Stem, root
Isoquinoline alkaloids, curine, hayatin.
Sedative, hypnotic, in rheumatism, gout & hypertension. Antioxytocic, Aphrodisiac, antidysentric. Bacteriostatic agent, in atherosclerosis, hypotensive Veneral disease, curare like activity.
Root
Isobutylamides
Rheumatic disease.
Fruit
umbelliferone
Root, & rhizome
Aristolochic acid
Diuretic, urinary antiseptic. Bitter tonic
Bark
Berberine, palmatine, phellodendrin
Seed, root bark, fruit Root
Berberine, palmatine, jatrorrhizine, columbamine
Immunomodulators and Adaptogen 1.
Arnica
2
Ginseng
3
Ashwagan dha
Withania somnifera (Solanaceae)
4
Shatavari
5
Garlic
Asparagus racemosus (Liliaceae) Allium sativum (liliaceae)
6
Gulvel
7
Echinacea
8
Saw palmetto Serpentar y
9 10
Phelloden dron
11
Darhald
12
Sophora
Tinospora cardifolia (Minispermaceae) Echinacea purpurea (Compositae) Serrenoa serulata (palmae) Aristolochia clematis (Aristolochiaceae) Phellodendron amurensei (Rutaceae) Berberis aristata (Berberidaceae)
Sophora flaverscens
Metrin & oxymetrin
182
Bitter tonic, Detoxifier, Febrifuge. Dysmenorrhagia, hepatic dysfunction Bitter,diuretic, antipruritic
N.K. Sachan 183
13
Sinomeni um
14
Uncaria
15
Tulsi
16
Acanthop anax
(Leguminosae) Sinomenium acutum (Menispermacae) Uncaria tomentosa (Rubiaceae) Ocimum sanctum (Labiatae)
Leaves & root
Sinomenin
Anticomplement action
Bark
Pterotodin
Immunostimulant
Leaves
Eugenol, methyl eugenol, caryophyllin
Eleutherococcus senticosus (araliaceae)
Leaves, bark
Lignans- D,Eeleuthrocyte,
Antibacterial, spasmolytic, diaphoretic, air acne. Hypoglycaemic activity
Bacopa monnieri (scrophulariaceae) Convolvulus pleuricaulis (convulvulaceae) Boerhavia diffusa (nyctaginaceae)
Whole plant Whole plant
Brahmine, herpistine, saponin Betaine, evolvine
Diuretic, cardiotonic, antiperiodic Epilepsy, nerve tonic
Whole plant
Punarnavine, ursolic acid, arachidonic acid
Rosa damascene (rosaceae) Matricaria chamomilla (compositae) Cyprus esculentus (cyperaceae)
flower
Volatile oil
flower
α-bisabolol, herniarin chamazulene, farnesene
Diuretic anti-inflammatory activity Astringent, aperient, Splenomegaly,
seed
Sesquiterpne, hydrocarbons, epoxide, ketones
Anyiinflamatory, antipyretic, antiemetic
seed
Castanospermine
Anticancer
root
Glycyrrhizin
seed
Gossypol
Demulcent, peptic ulcer Male contraceptive
Root
Tripterifordin
Anti leukaemic agent
Dried flower & aerial part Leave,
Hypericin
Sedative
Sulphated
Antiallergic
Rejuvenating drugs 17 18
Brahmi buti Shankhpu shpi
19
Punarnava
20
Rose
21
Gul babunah
22
Habulzilla m
Anti AIDS Drugs: 23
Castano – spermum
24
Glycyrrhi za Cotton
26
Triplerygi um
27
Hypericu m
Castanospermum australe (leguminosae) Glycyrrhiza glabra (leguminosae) Gossypium herbacium (malvaceae) Triplerygium wilfordie (celastraceae) Hypericum species (guttiferae)
28
Prunella
Prunella vulgaris
25
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(labiatae)
stem & flower
polysaccharide
Anti-inflammatory
Catharanthus roseus (apocynaceae) Cephalis acuminate (rubiaceae
Whole plant
Vincristine, vinblastine, reserpine
Hypotensive
Dried root &rhizo me Dried stem& root Dried root & rhizome
Cephaline, emetine
Expectorant, emetic
Camptothecin
Antiherpes, Antiadeno virus activity
α&β peltatin, podophyllotoxin
Purgative
Bark
Taxol
Root
Phyllanthostatin,phylla nthiside
Rheumatism, Fever Induce Abortion Astringent
Tubers
4 ipomeanol
Aphrodisiac Astringent
Anticancer Drugs: Vinca 29
Ipecac
30
Campothe ca
31
Podophyll um
32
Camptotheca acuminate (nyssaceae) Podophyllum peltatum, P. Hexandrum (berberidaceae) Taxus brevifolia (Taxaceae) Phyllanthus acuminatus (Euphorbiaceae)
33
Yew tree
34
Phyllanth us
35
Brazilian arrowroot
36
Surinjan
Colchicum autumnale (liliaceae) Hypolipidemic and anti atherosclerotic:
Seed, corm
colchicine, demecolcine
Gout
37
Guggul
Commiphora wrightii (Burseraceae)
Guggulosterone (E&Z), guggulosterol, mukulol
Arthritis, Rheumatism
38
Salai guggul
Boswelia serrata (Burseraceae)
β Boswelic acid, serratol, triterpene acid
Rheumatism
39
Garlic
Oleo gum resin from the injured bark Oleo resin from trunk portion Bulb
Allin, allyl sulphide
Immunomodulator, hypoglycemic
40
Vijayasar
Dried
Kinotannic acid
hepatoprotective
Ipomoea batatus (convolvulaceae)
Allium sativum (liliaceae) Hypoglycemic Drugs: Pterocarpus
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N.K. Sachan 185
marsupium (leguminaceae)
juice of the plant seed
Ellagic acid
hepatoprotective
seed
Gum (galactomannan)
Bulk laxative
leaves
Gymnamic acid, gymnestrogenin, gymnemagenin, nonacosane Charatin, monordicin
Liver tonic, antiinflammatory, emetic, diuretic, Dyspepsia Blood purifier
Ascaridole
Veterinary practice
Filixic acid
Anti viral, febrifuge Anti-inflammatory Febrifuge Digestive
41
Jamun
42
Guargum
43
Gurmar
44
Bitter gourd
Momordica charantia (cucurbitaceae) Anthelmintic Drugs:
fruit
45
Chenopod ium
Chenopodium ambrosoides var. antihelminticum (Chenopodiaceae)
46
Male fern
47
Artemisia (worm seed) Kapur kachari
Dryopteris filixmas (polypodaceae) Artemisia cina, Artemisia maritima (compositae) Hedychium spicatum (zingiberaceae)
Volatile oil from leaves, flowerin g and fruit part. Whole fern F lower
48
Syzgium cumini (Myrtacae) Cymopsis tetragonolobus (leguminosae) Gymnema sylvestre (Asclepidiaceae)
Santonin
Shoot
Volatile oil, starch
Stomachic, emmenagogue, diarrhoea.
Ruta graveolens (Rutaceae)
Whole plant
Furanocoumarins, acridone alkaloids
Antispasmodic, antiepileptic
Digitalis purpurea (schrophulariaceae)
Dried leaves
Purpurea glycosides A, B, D, E
51
Digitalis (Fox glove) Digitalis
Digitalis lanata (Scrophulariaceae)
Dried leaves
Lanatosides A, B, C
52
Thevetia
Seed
Thevetin
53
Adonis
Thevetia nerifolia (Apocynaceae) Adonis vernalis (Ranunculaceae)
Dried overgro und
Adoniotoxin, K – stropahanthin
Atrial fibrillation, supraventricular tachycardia Atrial fibrillation, supraventricular tachycardia Abortifacient , purgative,emetic. Tranquilizer
49
Sudab
Cardiotonic Drugs: 50
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186 Biodiversity, Biotechnology and Traditional Knowledge
54
Squill
Urginea indica (Liliaceae) 55 Strophant Strophanthus hus kombe (Apocynaceae) 56 Strophant Strophanthus hus gratus 57 Arjuna Terminalia arjuna (combetraceae) Liver Protecting Drugs: 58
Kalmegh
59
Picrorhiza
60
Phyllanth us
61
Silybum
62
Long piper
Andrographis panniculata (Acanthaceae) Picrorhiza kurroa royalae (Schrophulariaceae ) Phyllanthus amarus, P. Urinaria (Euphorbiaceae) Silybum marianum (Compositae) Piper longum (Piperaceae)
portion Dried Bulb Seed
Strophanthidin
Rodenticides, (in red squill) Tincture
Seed
Ouabain
Anticoagulant
Bark
Tannin, triterpenoid saponins
Diuretic, astringent
Entire arial portion Root and rhizome
Andrographoids, Flavonoids
Stomachic, cholagogue
Picroside, kutkoside
Bitter tonic
Phyllnthin, Phyllanthidin, Hypophyllanthin, Niranthin Silybin, silandrin, silymonin Piperine
against hepatitis B virus
Scillaren A and B
Entire plant Leaf and fruit Root
Bitter tonic Febrifuge, stomachic, analgesic
Antileprotic Agents: 63
Chaulmoo gra oil
Hydnocarpus wightiana (Flacourtiaceae)
64
Kala zeera
Nigela sativa (Ranunculaceae)
Oil from the fresh ripe seeds Seed
Hydnocarpic acid, chalmougric acid, garlic acid
Anti tubercular
Alkaloid, volatile oil
Diuretic, mercury poisoning
Psoralea corylifolia (leguminosae) Ammi majus (umbelliferae)
Fruit,se ed
Flavonoids, fixed oil psoralidin, psoralen,
Stomachic,anthelmenthic ,diuretic
Fruit
Psoralen, bergapten, xanthotoxin
Treatment of Vitiligo
Calotropis procera
Latex,
Asclepin, bacterioletin.
Purgative, emetic,
Antilucodermal Plants: 65
Babchi
66
Ammi majus Anticoagulants: 67
Safedak
186
N.K. Sachan 187
68
Papaya
(Asclepidaceae) Carica papaya (Caricaceae)
root Fruit, seed
Pappain, benzyl thiocarbamide, carotenoids
rheumatism Digestive, Diuretic,
Antidiarrhoel and Antidysentrics 69
Kurchi
70
Ipecac
71
Zeera
72
Mango
73
Madar
74
Amla
75
Acorus
76
Jawashir
77
Isaphgol
78
Bael
79
Pale catechu Rhubarb
80
Holarrhena antidysentrica (Apocynace) Cephalis ipecacuanha (rubiaceae) Cuminum cyminum (Umbelliferae) Mangifera indica (Ancardiaceae) Calotropis gigantean (Asclepidaceae) Phyllanthus embelica (Euphorbiaceae) Acorus calamus (Araceae) Ferula galbaniflua (Umbelliferae) Plantago ovata (Plantaginaceae) Aegle marmelos (Rutaaceae) Uncaria gambier (Rubiaceae) Rheum officinalis (polygonaceae)
Bark, root, seed Root and rhizome Dried ripe fruit Bark
Conessine, Nor connessin, kurchin
Stomachic,dropsy, febrifuge
Emetin, cephalin
Emetic
Cumin aldehyde
Carminative
Poly phenol, cynogenic glycosides Mudarine, asclepine
Diaarrhoea Diarrhea
Flower, fruit
Trigloyl glucose and other tannins
Liver tonic, source of vit C
Rhizom e Fruit
Volatile oil sesquiterpine, asarone Sesquiterpine,umbellife rone Mucilage
Carminative, sedative,epilepsy Carminative,expectorant
Marmelosine, tannins
Bulk laxative
Bark, leaf Rhizom e
Catechin, catechu tannic acid Rhein, other anthraquinone glycosides
Astringent
Stem, aerial part leaf
Ephedrine, Pseudoephedrine
Hay fever
Vasicine, vasicinone Lobeline
Oxytocic, expectorant Respiratory stimulant,
Volatile oil
Expectorant
Root , flower
Seed, husk Fruit
Bulk laxative
Laxative
Antiasthamatics: 81
Ephedra
Ephedra sinica (gentiaceae)
82
Vasaka
83
Asthma weed
Adhota vasica (acanthaceae) Lobelia inflata (lobeliaceae)
84
Tukhm-igandana
Nigelia indica (Ranunculaceae)
Entire plant Seed
187
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Antihypertensive Drugs: 85
Rauwolfia
Rauwolfia serpentina (apocynaceae)
Rhizome & root
86
Vinca
Catharanthus roseus (apocynaceae)
Flowerin g shoot & leaf
87
Porprang
Whole plant
88
Nutgrass
Convolvulus pluricaulis (convulvulaceae) Cyprus rotundas (cypraceae)
89
Olive oil
Oleaeuropoea (Oleaceae)
Fruit &leaf
90
Visnaga
Ammi visnaga (Umbelliferae)
91
Veratrum
Veratrum viride, V. album (Liliaceae)
Khellin, visnagin, khellolglycoside ,samidine . Jeveratru m, ceveratru m, proto veratrin
Ajmaline, ajmalinine, ajmalicine,serpentine, serpentinine reserpine, rescinnamine Ajmalicine, serpentine, tetrahydroalstonine, vincristine, vinblastine Sanghpushpine, α-β pinene
Root & seed
Cardiac arrythmia, neuropsychiatric disorder Hodgkins disease, lymphocytic leukaemia, lung,cervical & breast cancer Antiulcer, mental stimulation
Sesquiterpene, hydrocarbon, epoxides Triglycerides of oleic,palmitic & linoleic acid. Fruit
Anti inflammatory, antipyretic, anti emetic Laxative
Rhizome,roots
Arrythmia
Seeds
Physostigmine, physovenine
Atropine poisioning
leaves
Pilocarpine, pilosine
Emetic, Febrifuge, Diuretic, Dropsy, Lactagogue,
Smooth muscle relaxant, asthma
Anticoagulant Drugs: 92
Calabar bean
93
Jaborandi
Physostigma venonosum (Loganiaceae) Pilocarpus jaborandi (Rutaceae)
PROTECTION AND PRESERVATION OF KNOWLEDGE HERITAGE: The traditional Indian system of medicine has a very long history of usage in a number of diseases and disorders, but lacks recordrd safety and efficacy data. Ensuring that traditional medicinal knowledge is not lost (preservation) and that its originators are given credit and appropriate reward for their inventions (protection) is a strong immediate call for scientists, pharmacists and healthcare professionals. At the international level, the World Organization of Intellectual Property (WIPO) develops guidelines and legislative options for the protection of traditional knowledge. The CSIR Govt. of India has started a TKDL (traditional knowledge digital library) to protect the knowledge of plants and practices existing in India as a
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part of cultural heritage so that these can be protected from getting patented by other western countries as it happen with HALDI. For further exploration and validation of this knowledge under modern scientific background, there is a provision of new idea fund from CSIR may be granted if sufficient potential for a particular novel research is demonstrated. Unfortunately, India is yet to achieve this kind of intellectual repositioning. It continues to be depicted through “caste, cows and curry” images all too often. Indian culture is frequently portrayed as being mystical in the sense of being irrational, and in lacking a sense of advancement in the material plane of society. History of India's science and technology has not yet been attempted, though many of the elements have been well discussed in particular studies. Those who take a rather spiritual – even perhaps a religious – view of India's history do not have a great interest in the analytical and scientific parts of India's past, except to use it as a piece of propaganda about India's greatness (as in the bloated account of what is imaginatively called ‘Vedic mathematics', missing the really creative period in Indian mathematics by many centuries). On the other hand, many who oppose religious and communal politics are particularly suspicious of what may even look like a ‘glorification' of India's past. FUTURE PERSPECTIVES: The future possibilities for the integration of ethnopharmacology and traditional medicine place us at an exciting juncture. The world truly stands to benefit from the wealth of knowledge that is a part of traditional medicine. On the other hand, traditional medicine offers the impetus to move forward to western medicine, to try and understand the complexity of a different system of healing. Building an understanding of how and why traditional medicines work can only help to elucidate the equally complex factors that affect health. For those people involved, it may become the case that they have to turn their attention towards advocacy and ethics, looking at their work as a catalyst for international development and collaboration. In developing a vision for the future, the integration of ethnopharmacology and traditional medicine provides the international community with a unique opportunity to look at health as a holistic approach and right that can and must be provided to all segments of humanity. With this exciting possibility as the premise, it is time to truly begin to work on bringing traditional medicine and modern medicine together into a partnership to create an equitable system of health. Thus, the newer, safer and effective drugs will remain just a spin off and research continues keeping our hope for block-busters alive. There are several advantages associated of such a research strategy. Of course, relying on the experience accumulated by the humankind through the centauries serves a kind of screen for the biological activity. And the experimentation with the plant resources that are having traditionally sound biological activity has greater probability to produce positive results on biological screen. Therefore the time and expenditure required for synthesizing millions of compounds and subsequent biological screening to get a lead compound can be reduced significantly by concentrating the research over phytoconstituents of such plants for the biological activity rather than going for a random screen. The research can be hastened by implementing such a strategic drug discovery program as it dramatically cuts the time of laboratory research to arrive to the production of an efficacious medicine. Also, from an economic viewpoint, production of medicines on the basis of past knowledge and with local natural resources sharply reduces the cost and can alleviate the budget of public health services. Moreover, the biological activity of natural products is not limited to one or a couple of actions, but is broader spectrum that includes agents susceptible to compensate for possible side effect(s) of the main component(s). Exploring the natural remedies offers a better chance for sudden discovery of some therapeutically active principle that might be present in the plant but not as a major component, and whose therapeutic action may not considered in the research. CONCLUSION: In conclusion, the body of existing ethanomedicinal knowledge has a vide prospect in the drug discovery and development, providing the potential plant candidates for desired therapeutic activity, and thereby can reduce the cost and time of drug development. There is also a need to develop and screen a large number of pure compounds and plant extracts which remained only an academic exercise in universities, for possible industrial usage. Some semisynthetic modifications in the plant derived products can also be tried
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to improve the therapeutic activity and safety profile of the phytopharmaceuticals by applying the SAR / QSAR, CADD and genomics & proteomics based approaches. India needs a clear policy for such integration without compromise on the strategies that are science based. Here, till very recently, collection of ethanomedicinal information remains primarily an academic endeavor of little interest to mot industrial groups. Therefore, with rapid industrialization of planet and loss of ethnic cultures and customs some of this information will no doubt disappear. India need to document its abundant ethenomedicinal information on plat use in usable form, protect it and should promote to integrate to drug discovery and development processes. REFERENCES: 1.
Dolui, A.K., Das, S., and Chetia, D. (eds.) (2002) Management of Natural Resources for Better health care. Proc. of the national seminar on harnessing science and technology for health for all with special reference to north east India, Department of Pharmaceutical Sciences, Dibrugarh University, Sep 2001.
2.
Young-Won Chin, Marcy J. Balunas, Hee Byung Chai, and Douglas Kinghorn (2006) Drug discovery from natural resources. The AAPS Journal; 8(2): E 239 – 50.
3.
Touwaide A. (2005) Exploring Traditions. Editorial Note. Iranian Journal of Pharmaceutical Research. 2: 61 – 62.
4.
Proceedings of the National Seminar on Value Addition to Bio-resources of Northeast India at Gauhati University on the occasion of national technology day 2006.
5.
Proceedings of the workshop on WTO: Outreach and Advocacy, March 24-25, 2006 Dept. of economics. Dibrugarh University.
6.
Proceedings of National Conference on Current Status and Challenges in Pharmacy and Health care, March 28, C.S.J.M. University, Kanpur.
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