Indian Journal of Traditional Knowledge Vol. 9(1), January 2010, pp. 18-25

High altitude botanicals in integrative medicine-Case studies from Northwest Himalaya

M K Kaul Biodiversity and Applied Botany Division, Indian Institute of Integrative Medicine, Jammu 180 001, Jammu & Kashmir E-mail: [email protected]

Emerging trends of underutilization of high altitude medicinal by Indian phytopharmaceutical industry suggest that therapeutic potential of these species has been exploited to a very less extent despite availability of rich traditional knowledge and also greater possibilities of offering novel bioactive compounds. According to a recent estimate only 20% high altitude medicinal plants available in Indian subcontinent (predominantly herbs) are used in drug trade. In , we often wake to our own therapeutic wisdom only after recognition comes from the west. High altitude herbal medicines offer therapeutics for many disorders like memory loss, osteoporosis, immune and age-related problems, etc. particularly the ones for which no modern medicines are available. Of late, these plants are also reported to offer satisfactory therapies for deadly diseases like AIDS and cancer. As high altitude plants are growing under stressful situations and exposed to high UV radiations, they are reported to have immense potential in biological radioprotection. An attempt has been made to highlight the promise that these stress-tolerant plants hold in alleviating human and veterinary ailments with less side effects. Studies on the characteristics of ethnopharmacological resources in high altitude Northwest Himalayan region revealing use of 154 botanicals in home remedy patterns of 55 common ailments as well as integration of food and medicine in several traditional herbal therapies are discussed and included in the text.

Keywords: High altitude medicinal plants, Therapeutic promise, Traditional medicine, Ethno-medico-botanical leads IPC Int. Cl. 8: A61K36/00, A61P

High altitude regions are characterized by cold and species 2-4. Due to species climatic and geophysical arid climate, scanty rainfall, high wind velocity, snow conditions, temperate and alpine plants of the storms and blizzards and high ultraviolet (UV) Himalaya offer greater possibilities of having novel radiation. Vegetation in these regions exhibits a molecules and even largest quantities of active characteristic adaptation to the extreme environmental compounds 5,6 . Herbal drugs of montane ecosystems, conditions. The compression of thermal life zones and constituting only those traditional medicines which the fragmentation of the landscape into a multitude of primarily use medicinal preparations for microhabitats are main factors leading to large habitat therapy, are in vogue in high altitude regions and diversity. These microhabitats represent archipelagoes offer great therapeutic promise. Presently, these of peculiar life forms of medicinal plants and are herbal medicines also find market as nutraceuticals considered to be hotspots of medicinal plant whose current market is estimated at about $80-250b biodiversity. In global context, the Himalayas form an in USA and also in Europe. Plant derived drugs interrupted mountain range extending across 3,500 constitute important monographs in German and km from to China. They host some 7,000 Russian Pharmacopoeias. Even now, almost 70-80% species of medicinal plants 1. India and China are two of world population depends on crude plant drug largest countries in Asia known for strong traditional preparations to tackle their health problems. medical systems and rich diversity of medicinal The turnover of herbal medicines in India as over plants. Unlike China, India has not been able to the counter products, ethical and classical capitalize on herbal wealth by promoting its use in formulations and home remedies of Ayurveda , Unani developing world. The information on medicinal and Siddha systems of medicine is about $1b with a plants (MPs) of high altitude regions in Indian meager export of $80m 7. Export of herbal medicine Himalayan Region (IHR) is fragmentary, though out from India is negligible despite the fact that the of 700 MPs used by entire Indian drug industry, country has a rich traditional knowledge and heritage Himalayan medicinal plants contribute roughly 350 of herbal medicine. This is in view of lack of KAUL: HIGH ALTITUDE BOTANICALS FROM NORTHWEST HIMALAYA 19

standardization and quality control of our herbal antineoplastic lignan podophyllotoxin, a constituent of products. In India, there are about 7,000 firms in Podophyllum hexandrum –a high altitude medicinal small scale sector manufacturing traditional medicines herb, are currently being used against testicular cancer, with or without standardization. Major traditional small cell lung cancer and lymphomas 9. Similarly pharma sectors, namely Himalaya, Zandu, Dabur, taxol, a diterpenoid constituent of Taxus wallichiana a Hamdard, Baidyanath, Maharishi, etc. and modern high altitude tree species is effective in the treatment of pharma sector namely Ranbaxy, Lupin, Alembic, etc. metastatic ovarian cancer, and has potential uses in the are standardizing herbal formulation through various treatment of lung cancer, metastatic breast cancer and techniques. A recent report on medicinal plant malignant melanonoma 10,11 . These species have been scenario in India prepared by FRLHT (Foundation for declared as critically endangered in view of the Revitalization of Local Health Traditions, 2002) has destructive harvesting from their wild habitats. Large listed 20% of high altitude medicinal plants in Indian scale cultivation is needed to save these species from drug trade. A need was felt to put in the best extinction. In fact, development of new anticancer collective efforts to select plants with significant drugs from natural products available in these regions health potential. Out of 111 species of Indian is a challenging task which needs to be pursued more medicinal plants selected for monograph, only 16 are rigorously. from high altitude regions 8. Since, high altitude Another high altitude plant species–Hypericum regions are rich in endemic plant diversity and perforatum has become one of the important plants as a relatively lesser known pharmacologically as result of its unique spectrum of constituents and compared to tropical ones, the paper focuses on promising pharmacological and clinical profile. In therapeutic potential of the species occurring in an addition to hypericin, (napthodianthrone) hyperforin 10 altitudinal range of 1,700-5,000m. (phloroglucinol derivatives) has recently gained importance as a potent contributor to antidepressant Therapeutic promise of high altitude plants activity 12 . Antibacterial and antiviral activities of The therapeutic promise of high altitude medicinal Hypericum perforatum extracts has added to the plants (HAMPs) may be categorized into following 5 therapeutic promise of this species. Efforts are going major categories: on in IIIM, Jammu to develop a complete technology

HAMPs as source for treating major ailments package for production of quality raw material and also products of international standards. Some elite strains Modern drugs from traditional medicine (cases from HAMPs) with higher content of hypericin and hyperforin have already been developed and are being cultivated under Biological radioprotection (Cases from high altitudes) organic conditions adopting good agricultural practices Wealth of ethnomedicobotanical HAMPs (GAP). Ethnoveterinary medicinal plants from high altitudes Modern drugs from traditional medicine (cases HAMPs as source for treating major ailments from HAMPs) Out of the 10 best selling herbal medicines in Even in ancient cultures, people methodically and developed countries 5 are grown in high altitude systematically collected information on herbals and regions. These are Echinacea sp, Panax sp, Ginkgo developed well defined herbal pharmacopoeias. During biloba, gerardiana and Hypericum 20 th century, much of the pharmacopoeias of scientific perforatum . Amongst developed countries, Germany medicine were derived from herbal use of native holds the lead and has published individual people. Many modern medicines including codeine, monographs on therapeutic benefits of more than 300 morphine, atropine, hyoscyamine, ephedrine, quinine, herbs 7. It must be recognized that out of the 16 species colchicine, digoxin, strychnine, reserpine, artemisinin, of Indian medicinal plants from high altitudes selected taxol, ergot, etc. are of herbal origin. About one-quarter for individual monographs most of the plant based of the prescription drugs dispensed in community introductions have been innovative in character, and pharmacies in the USA contain at least one active represent outstanding contributions to therapeutics8. ingredient derived from plant materials. Modern drug Major high altitude medicinal plants with established discovery is mainly based on indigenous cure in therapeutic claims are listed (Table 1). For example folklore in one culture or the other. For example, the teniposide and etoposide developed from the use of belladona in Babylonian folklore brought this 20 INDIAN J TRADITIONAL KNOWLEDGE, VOL. 9, No. 1, JANUARY 2010

Table 1 −HAMPs with established therapeutic claims and used in some major ailments

Plant parts Potent principals Therapeutic claims Reference Aesculus indica Colebr. (Seed) Aescin, galactogogue Anti-inflammatory, antimicrobials 25 Artemisia annua Linn. Artemisinin Anti cerebral malaria 13 Atropa acuminata Royle Tropane alkaloids Anticholinergic 41 Dioscorea deltoidea Wall. Diosgenin and derivatives Steroidal activity 25 Echinacea angustifolia DC. Arabinogalactans Immunomodulator, antiviral 32 Ginkgo biloba Linn. (Leaf) Flavonoids, ginkgolides Treatment of cerebral and peripheral 38 circulatory disturbances Hypericum perforatum Linn. Hypericin, hyperforin Antidepressant, antiviral, 33 (Leaf, flower) Inhibits leukemia virus Panax ginseng (Root) Ginsenosides Adaptogen 34 Podophyllum hexandrum Royle (Root) Podophyllotoxin teniposide, Against testicular cancer, small cell lung 9 etoposide cancer, lymphomas Serenoa repens Small (Fruit) Polysaccharides Hypolipidaemic, treatment of 40 nonmalignant prostrate disease Swertia chirayita Karst. Secoiridoides Febrifuge 35 Taxus wallichiana Zucc. Paclitaxel Against ovarine cancer, lung cancer, 11 malignant malanoma Valeriana officinalis Linn. (Root) Sesquiterpene acids, valepotriats Sedative 25

Table 2 −Traditional modern drugs from HAMPs

Drug Plants name Basis of investigation Therapeutic use Reference Artemisinin Artemisia annua Linn. Chinese folklore Antimalarial 16 Atropine Atropa belladona Linn., A.acuminata Babylonian folklore Anticholinergic 36 Royle Colchicine Colchicum luteum Baker European folklore Antigout 36 Digoxin Digitalis lanata Enrh. European folklore Cardiac stimulant 36 Ephedrine Ephedra gerardiana Wall. Chinese folklore Bronchodilator, 37 antiasthmatic Hyoscyamine Hyoscyamus niger Linn. Babylonian folklore Anticholinergic 37 plant into lime light in modern medicine. Similarly, 2,000 yrs 14,15 . Chinese Pharmacopoeia of 1990 lists 784 Ephedra was known in Chinese folklore to be used traditional Chinese drugs, of which 630 are of plant against respiratory disorders and asthma and ephedrine origin 16,17 . Therapeutic activity of some of the established a drug of modern medicine. The use of important HAMPs from Chinese Herbal traditional folklores of some medicinal plants growing Pharmacopoeia is listed (Tables 3 & 4). Chinese plant in high altitudes and temperate climates for making Sophora substrata (roots) has been used in China for drugs of single chemical entity have been enlisted treatment of stomach trouble and sophoradin, a (Table 2). One of the striking examples is extraction of chalkone isolated from this has shown significant anti- compound artemisinin–sesquiterpene peroxide active gastric ulcer activity 18 . Huperzia serrata has been used against both chloroquine-sensitive and chloroquine- traditionally in China to alleviate memory disorders of resistant strains of Plasmodium falsiparum and P. the elderly. An alkaloid-huperizine A isolated from this vivax , and equally effective against cerebral malaria 13 . plant has been demonstrated to be a powerful Similarly hyoscyamine–a tropane alkaloid is being acetylcholine esterase (AchE) inhibitor, for the used extensively in modern medicine as treatment of Alzheimer disease. In India, anticholinergic. Even digoxin is still considered to be a pharmaceutics occupies an important place in good cardiac stimulant, although many drugs in Ayurveda . Medicinal preparations are invariably modern medicine started replacing its use. complex mixtures derived from plants, animal products Traditional medicinal systems (eg. Zhong yao in and also minerals and metals. Plants form a dominant Chinese, Kampo in Japanese) have been practiced in part of Ayurvedic pharmacopoeia. Charaka Samhita China, Japan and other far eastern countries for past (900 BC) is the first recorded treatise fully devoted to KAUL: HIGH ALTITUDE BOTANICALS FROM NORTHWEST HIMALAYA 21

Table 3 −Therapeutic activity of some high altitude medicinal plants used in Chinese medicine Plants name Active components Major action Agrimonia pilosa Ledeb. (Whole plant) Agrimol A, B, C, D & E Antimalarial in mice Ajuga decumbens wall.ex Benth. (Whole plant) Luteolin Antitussive Arnebia euchroma Johnston (Root) Shikonin derivatives Treatment of hepatitis Artemisia scoparia Waldst. & Kit. Chlorogenic acid, caffeic acid Choleretic for treatment of jaundice or (Young shoot) cholecystitis Daphne genkwa Siebold & Zucc. Yuanhuacine A, yuanhuacine B Induces premature abortion Daphne giraldii Nitsche(Root bark) Daphnetin Analgesic Descurainia sophia Webb ex Prantl (Seed) Strophanthidine, evobioside, evomonside, Cardiotonic, diuretic rysimonside, helveticoside Fagopyrum cymosum Meissn. (Rhizome)  Pulmonary abcess Hypericum japonicum Thunb. (Whole herb) Total flavonoids Acute or chronic hepatitis Lonicera japonica Thunb. (Flowers) Chlorogenic acid, isochlorogenic acid Treatment of viral infection Rhododendron dauricum Linn. (Leaves) Germacrone, scopoletin Expectorant, Antitussive, asthmolytic Rhododendron mariae Hance (Leaves) Matteucrinol Antitussive Rhododendron molle G. Don (Fruit) Rhomotoxin Antihypertensive and trachycardia Rorippa dufia Hara (Whole herb) Rorifon Expectorant, antitussive Swertia mileensis T. N. Ho & W.L. Shih Oleanolic acid Treatment of hepatitis (Whole herb) Wikstroemia indica Mey (Root) Daphnoretin Improves nutrient, blood flow of heart

Table 4 −HAMPs holding future therapeutic promise

Plant name Constituents Therapeutic claims Reference Aesculus hippocastanum Linn. Triterpenic saponin CVI (Chronic vexous Insufficiency) 25 Craptaegus oxycantha Linn.  Effective in congestive heart failure 25 Ginkgo biloba Linn. Flavanoids Cerebral disorders, demention 38 39 Picrorhiza kurrooa Royle ex Benth. Picrosides C, androcin, Hepatoprotective, anticancer, antiasthmatic 27 cucurbitacins Swertia chirayita Karst. Iridoides, secoiridoides Hepatoprotective, febrifuge 40 Valeriana jatamansi Jones / V. officinalis Valepotriates Increases GABA-secretion 27 Linn. Viola odorata Linn. Viola-quercitin (glycoside) Used in bronchitis and throat infections 41 concepts of Ayurveda . Plant based drugs have been whole plant or its parts eliciting radioprotective classified as per their therapeutic action. Charaka efficacy contains a large number of bioactive places his drugs in 50 groups and Sushruta divides molecules like antioxidants, immunostimulants, cell these into 37 categories 19,20 . It is estimated that a total proliferation promoters, cytokines, etc. which may of 1,000 Ayurvedic remedies prepared from individually or in combination render protection approximately 750 plants, are being used at present21 . against radiation induced pathology. The toxic effects generated could be countered by several other types Biological radioprotection (Cases from high of molecules present in whole extract. A high altitude altitudes) shrub, Hippophae rhamnoides is reported to be a Radioprotectors are the substances of different strong antioxidant and effective radioprotectant origin that increase body resistance to radiation because it contains large number of molecules like exposure. A number of plant products have been flavones, flavonoids, vitamin A, C, E and K, tannins evaluated for radioprotection action 22 . Identification and various trace elements like Se, Zn, Cu and S 24 . of non-toxic radioprotective agents is of considerable interest for radiation medicine. A large number of Wealth of ethno-medico-botanical HAMPs chemical and biological agents have been screened In reality, its full complexity is difficult to fully and reviewed 23 . In case of plant species, extracts of understand. All of us create our own images or 22 INDIAN J TRADITIONAL KNOWLEDGE, VOL. 9, No. 1, JANUARY 2010

models of reality. Holders of indigenous knowledge a traditional prescription may include some make their own models in their minds about the botanicals, which have been selected to address the botanicals, and when research scientists conduct particular site of pathology, others to stimulate a more studies or experiments, they formulate hypotheses and generalized immune response, still others to offset construct formal models as per their understanding. side-effects in some of the ingredients, and others to Ethnobotanical studies carried out under an ambitious increase cellular uptake. This complex approach to All India Coordinated Research Project on pharmacology is based on a concept of ‘synergistic Ethnobiology (1982-1992) revealed that >8,000 plant activity’ of the multiple components in a traditional species possess ethnomedicinal significance. These formula. Fifteen important HAMPs were found to be studies brought to light the ethnomedicinal properties effective against single or multiple ailments (Table 5). of 300 plant species from high altitude regions 25 . As These herbs are administered singly or in combination per an estimate, IHR supports 1,748 (23.2%) of Indian of two to four different plant materials. The concept medicinal plant species, out of which 1,685 are of health foods and integration of food and medicine angiosperms, 12 gymnosperms and 51 are is very old in high altitude regions. During pteridophytes 26 . A small proportion (10%) of ethnobotanical studies, >150 species used as wild medicinal plants from IHR, which is considered to be edibles in higher altitudes were identified. In higher a repository of high altitude medicinal plants, is being Himalayan region, ‘mini health food banks’ are utilized by major Indian pharmaceutical companies. It available in every household for ensuring food is also estimated that >50% of identified medicinal security and healthcare during drastic prolonged plants in IHR occur as herbs in temperate/alpine winters which gets extended to 8 months a year. Some regions. Out of which, >20% are native and over promising plant materials used as health foods in high exploited 4. altitude regions have been enlisted (Table 6). A study on the characteristics of Nutritional evaluation was carried out at IIIM, Jammu ethnopharmacological resources in high altitude (Table 6). Three species as case studies from the regions of NW Himalaya conducted by IIIM Jammu, western Himalaya are described hereunder: revealed that 154 botanical items are used to treat Urtica hyperborea Jacq. Himalayan Nettle; Zachut more than 55 ailments identified in this region 27 . This in Tibetian language study revealed that there is a definite impact of ethno- Collected by local communities and nomadic tribes medico-botanicals of this region on the general from wild and after shade drying it is stored at home. healthcare system of different communities. The Considered to be highly nutritious and given before herbal mixtures form the basis of prescriptions and and after child birth (pre and postnatal food for these are frequently prepared through a process which women) for general vitality. Plant samples from wild may include drying, crushing, heating, boiling, even and house hold material when evaluated gave reducing to a form of ash. The multiple ingredients in nutritional composition per 100 gm as: protein (17.75

Table 5 −Selected ethno-medico-botanicals from high altitudes

Plants name (Parts used) Ethnobotanical use Achillea millefolium Linn. (Shoot) Swollen gums and frost bite Aconitum heterophyllum Wall. ex Royle (Root) Antipyretic Acorus calamus Linn. (Rhizome) Excessive bile formation Arnebia benthami Johnston (Shoot) Antipyretic, flowers cardiotonic Artemisia absinthium Linn. (Shoot) Anthelmentic, skin eruptions Artemisia maritima Linn. (Shoot) Anthelmentic Atropa acuminate Royle (Leaf, Root) Wounds, swellings, boils Bergenia ligulata Sternb.(Root) Sores and menstrual cramps Equisetum ciliata Linn. (Shoot) Diuretic, antidiabetic Fritillaria roylei Hook. (Corm) asthma, aphrodisiac Lavatera kashmiriana Mast. (Shoot, Root) Abdominal disorders, renal colic Picrorhiza kurroa Royle ex Benth. (Root) Antidysenteric, enlargement of liver Polygonum amplexicaule D. Don(Root) Herbal tea, cardiotonic Rheum emodi Wall. ex Meissan (Root) Swellings, wounds Saussurea costus (Falc.) Lipsch. (Root) Rheumatic pain KAUL: HIGH ALTITUDE BOTANICALS FROM NORTHWEST HIMALAYA 23

Table 6 −Promising cases of integration of food and medicine in high altitude regions

Plant name/Parts/ Altitude (m) Ethnomedicinal use Nutritional composition (on dry wt. basis) (g/100gm) (mg/100g) Crude protein Crude fibre Carbohydrates total Na Ca Fe P Cicer microphyllum Benth. Against mountain 19.10 3.82 43.55     (Seed/ 4000-5000) sickness/stress Dipsacus inermis Wall. Stomachic & carminative 16.25 13.10 50.85 451 2379 83 285 (Leaf/2000-3500) Polygonum alpinum All. Root extract used in 10.75 12.10  1100 115 345 200 (Shoot, root/ 2500-3500) chronic backache Urtica hyperboea Jacquem. Post natal energizer 26.75 5.57 34.68 75 297 41 266 ex wedd. (Leaf/4000-5000) gm), crude fibre (5.57 gm), sodium (75 mg), calcium are needed to identify the bio-active molecules from (297 mg), phosphorus (266 mg) and iron (41 mg) 28 . these herbs. Polygonum alpinum All (Polygonaceae); Chita Opportunity hola in Kashmiri language High altitude ecosystems are considered to be Water extract of the dried root powder is used to hotspots of medicinal plant diversity and are most prepare rice and fed to arthritic patients. Even poultice neglected/virgin areas for research in view of their prepared from the roots along with the crushed seeds inaccessibility and harsh climatic conditions. As per an of Medicago falcata is put on aching joints. The plant estimate only 20% high altitude medicinal plants are is common on alpine slopes in temperate Himalaya. used in Indian drug trade and all are being collected Analysis of the root samples (100 gm) revealed from wild sources. Pharmacologists opine that there are presence of protein (10.75 gm), fibre (12.01 gm), greater possibilities of the presence of bioactive starch (12.70 gm), calcium (115 mg), potassium (1.2 29 molecules in high altitude plants in view of their mg), phosphorus (200 mg) . completion of life cycle under stressful situations. Dipsacus inermis Wall. (Dipsaceae); Wopal hack Therapeutic potential of these medicinal plants has in Kashmiri language been explored sporadically, which is almost negligible The leaves collected in large quantity, dried in looking to the wealth of knowledge that exists. With shade and used as vegetable on auspicious occasions. the advent of synthetic drugs in the last century, the use This has stomachic and carminative properties. of herbal medicine was overlooked resulting in the loss Analysis of leaves per 100 gm revealed presence of of valuable knowledge on medicinal plants. However, protein (16.25 gm), fibre (13 gm), starch (11.3 gm), today, herbal remedies are booming than never before. calcium (2.4 mg), potassium (4.1 mg), sodium (45 30. The most convincing proof of this notion is provided mg), phosphorus (285 mg), iron (83 mg) by the two recent Harvard surveys showing that

Ethnoveterinary medicinal plants from high between 1990 and 1997 the usage of herbs by the altitudes general public in US has increased by a staggering Animal husbandry is the major occupation of the 380% . For UK, no reliable data are available but all pastoral communities and nomadic tribes living in the indicators suggest that the trend is similar. It cannot be high altitude areas of the Himalaya. These convincing, if it is not driven by science. While communities seldom have access to the modern medical herbalism thrives on intuition and veterinary medicines/doctors, therefore, they depend individualized plant mixtures, phytomedicine attempts on folk medicine and herbal remedies for treating the to understand the (complex) pharmacology, efficacy and safety of medicinal plants. diseases of animals. As a result of ethnobotanical studies carried out in IIIM Jammu from 1982-1988, Acknowledgement useful information on ethnoveterinary medicinal Author is grateful to authorities of IIIM Jammu plants was collected and documented. Veterinary (formerly known as Regional Research Laboratory, diseases like diarrhoea, colic, black quarter and red- Jammu) for encouragement to pursue research in high water are most common in Northwest Himalayan altitude biology during the last four decades. The region. In all, 18 herbs are reported which are used to financial assistance provided by MOEF, DBT and DST treat various diseases in livestock 31 . Further studies for undertaking various projects is acknowledged. As a 24 INDIAN J TRADITIONAL KNOWLEDGE, VOL. 9, No. 1, JANUARY 2010

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