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1 CHAPTER I INTRODUCTION 1.1 INTRODUCTION India is much known for its variety of agro-climatic diversity and also for its rich heritage of traditional systems of medicines. The Indian System of Medicine (ISM) comprises of Ayurveda, Siddha , Unani and Tibetan system of medicine along with the other folk medicinal practices and age old home remedies. All these systems have placed India, as the pioneering country, in natural medicinal therapeutic field, which is based on the traditional knowledge of the use of medicinal plants. India possesses a rich treasure of biodiversity, which has been used for health care, for the last more than four thousand years. Medicinal plants are those plants that contain substances which could be used for therapeutic purposes or which are precursors for the synthesis of useful drugs [1]. India has one of the oldest, richest and most diverse cultural traditions associated with the use of medicinal plants, including 15 distinct agro-climatic zones and 47,000 different plant species. Out of 1500 medicinal plants, 500 species are identified for the preparation of drugs. At present, there are, about 130 clinically tested prescription of drugs of known chemical structure, which are used in Modern Systems of Medicine and solely derived from about 100 species of higher plants. The medicinal plants account for about 80% of the raw materials used in the preparation of drugs. The effectiveness of these drugs mainly depends upon the appropriate use and sustained availability of the genuine raw materials [2]. This is rightly said, in the Indian old scriptures, about the intrinsic values of the plants: ^^ txR;soe~ vukS”/ke u fdafpr~ fo|rs nz O;e~ oRlukFkkZ ;ksx ; ** thod Meaning thereby “ There is no plant in the world which is non medicinal or which cannot be used as medicine-Jivaka [3].

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CHAPTER – I

INTRODUCTION

1.1 INTRODUCTION

India is much known for its variety of agro-climatic diversity and also for its rich

heritage of traditional systems of medicines. The Indian System of Medicine (ISM)

comprises of Ayurveda, Siddha , Unani and Tibetan system of medicine along with the other

folk medicinal practices and age old home remedies. All these systems have placed India, as

the pioneering country, in natural medicinal therapeutic field, which is based on the

traditional knowledge of the use of medicinal plants. India possesses a rich treasure of

biodiversity, which has been used for health care, for the last more than four thousand years.

Medicinal plants are those plants that contain substances which could be used for therapeutic

purposes or which are precursors for the synthesis of useful drugs [1].

India has one of the oldest, richest and most diverse cultural traditions associated

with the use of medicinal plants, including 15 distinct agro-climatic zones and 47,000

different plant species. Out of 1500 medicinal plants, 500 species are identified for the

preparation of drugs. At present, there are, about 130 clinically tested prescription of drugs

of known chemical structure, which are used in Modern Systems of Medicine and solely

derived from about 100 species of higher plants. The medicinal plants account for about

80% of the raw materials used in the preparation of drugs. The effectiveness of these drugs

mainly depends upon the appropriate use and sustained availability of the genuine raw

materials [2].

This is rightly said, in the Indian old scriptures, about the intrinsic values of the plants:

^^ txR;soe ~ vukS” /ke u fdafpr~

fo|rs n zO;e ~ oRlukFkkZ ;ksx ; ** thod

Meaning thereby “There is no plant in the world which is non medicinal or which cannot be

used as medicine”-Jivaka [3].

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In spite of the tremendous development of synthetic and antibiotic drugs during the 20th

century, the plants still constitute one of the major sources of safe drugs in the modern as

well as in traditional systems of medicine throughout the world. The Nature has been a

source of medicines over past many centuries and an impressive number of modern drugs

have been developed from the natural plant sources. The plant kingdom is the virtual

goldmine of potential drug formulation and other active principle constituents, awaiting to

be discovered. It has been estimated that only 10-15 percent of the 7,50,000 existing species

of higher plants have been surveyed for biologically active compounds [4]. According to

World Health Organization, medicinal plants would be the best source to obtain a variety of

drugs. Therefore, such plants should be investigated for better understanding of their

therapeutic properties, safety and efficacy [5].

A variety of medicinal plants have been widely used to treat many human ailments,

right from the time, since the knowledge of their therapeutic values and use came to the

human beings. Some of the ingredients of Allopathy and most of the Ayurveda and

Homeopathy medicines are derived from the plant sources. Even today, medicinal plants

provide a cheap and effective source of drugs for the greater number of the world‟s

population. Investigation of the chemical and biological activities of plants during the past

two centuries have yielded compounds for the development of modern synthetic drug

industry as a major path for the discovery of novel and more effective therapeutic agents [6].

Natural products produced by plants, fungi, bacteria, insects and animals have been isolated

as biologically active compounds. Approximately one third of the top selling drugs in the

world are derived from natural products. Moreover, natural products are widely recognized

in the pharmaceutical industry for their broad structural diversity as well as their broad range

of pharmacological activities [4].

1.2 INDIAN SYSTEM OF MEDICINE

Indian System of Medicine, knowledge is accessible from hundreds of medical texts

and manuscripts in the form of Samhitas, lexicons (Nighantu‟s) and regional commentaries.

This traditional wisdom forms the codified system of medicine and exists in the form of

Ayurveda, Siddha, Unani and Swa rigpa (Tibetan) systems of medicines. There are over

25,000 herbal products documented in medical literature. Also, there exists a vast

knowledge in the form of folk/ non-codified/oral traditions. Most of the indigenous systems

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of medicines are respected for holistic approach involving body as well as mind for treating

various diseases and ailments.

1.2.1 FOLK MEDICINES /ETHNO MEDICINE/ NON CODIFIED SYSTEMS OF

MEDICINE

Non codified systems do not have standard formats of therapeutic products, because

of the significant variations in the structure and methods of preparartion and the methods of

medicines administration in accordance with the traditional knowledge adopted by the

different communities, which are the carriers of this knowledge over generations and across

a large tract. For instance, some communities preserved and transferred this knowledge in

the form of folklore while others have preserved it in the form of legends, wall paintings etc.

It has been frequently observed that the transfer of this knowledge has been restricted to

particular kinds or groups of teacher and disciples. However, unwritten forms of knowledge

are obliviously more likely to be lost or altered over the passage of time, if not examined for

their claims and verified for their usage on scientific principles and ethics. The

ethnomedicines, on scientific verification may lead to the development of new modern

medicines. This aspect needs to be taken special care of.

1.3 CODIFIED SYSTEMS OF MEDICINE

1.3.1 AYURVEDA

The word “Ayur” means life and “Veda” means knowledge or science. Thus

“Ayurveda” is the science of life. Pandey et al. [3] summarized it as “a way of life

encompassing science, realization”. It aims to achieve the union of the physical, emotional

and spiritual health, known as swasthya- a state that enables an individual to enter into a

harmonious relationship with the cosmic consciousness.

It is believed that Ayurveda originated as early as 5000 BC in the Himalayan region

as a result of the holy and arduous pursuits of spiritually enlightened „Rishis‟. Ayurveda is

considered to be an ‘upaveda’ of Atharva Veda written somewhere around 3000 to 2000BC.

Though it had been practiced all along, it was around this time that oral wisdom of

Ayurveda was codified. It enlists eight branches of Ayurveda viz.

Kayachikista ( internal medicine)

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Shalaya Chikitsa (surgery & treatment of head, neck, ophthalmology and

otolaryngology)

Shalya Trantra (surgery system )

Agada Tantra (toxicology)

Bhuta Vidya (psychiatry)

Kaumarabhriya (pediatrics)

Rasayana (Science of rejuvenation) and

Vajikarana (science of fertility)

The oldest treatise available on codified version is Atreya Samhita. Around 1500 BC

Ayurveda was delineated into two main schools: “Atreya”-the school of physicians and

“Dhanvantari” the school of surgeons.

These two schools of thought led to the writing of two major books in 800 to 700 BC

viz “Charaka Samhita” and “Sushruta Samhita”, these comprised the knowledge about

medicines and surgery respectively. Later, around 500 AD Vagbhatt compiled a third major

volume on Ayurveda „Ashtanga Hridaya‟. This was a comprehensive work which

combined the knowledge from both the schools of Ayurveda mentioned above. From 500

AD to 1900 AD, 16 major texts of „Nighantu‟ or supplementary texts on ayurveda such as

„Bhavprakasha‟, „Raja‟ and „Shaligram‟ were written. These books, written in Sanskrit,

have made a mention of about 1,814 medicinal plants. Subsequently, a sizable literature has

been generated based on Ayurveda in many regional and local languages. An Ayurveda

based compliation of remedies-the Aryabhiahak [3] lists about 700 texts on Ayurveda and its

applications. Egyptians, Chinese, Romans, Arabs, Germans, Russians and British all took

interest in Ayurveda which led to a number of translations and compilations in their

respective languages.

The medicines used in Ayurveda are chiefly plant based, but a few drugs are also of

mineral and animal part origin. These are broadly described and classified under five

properties viz.

1. Rasa (taste-sweet, sour, salty, pungent, bitter & astringent)

2. Guna (attributes such as heavy, sharp, dry etc .)

3. Veerya (potency)

4. Vipaka (consequence or change that the drug undergoes in the human body) ,and

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5. Prabhava (dominating influence or effect of active principal constituent of the drug)

Evidence has shown that Ayurveda had contributed to almost all the medical systems

and a progenitor of the Unani, Tibetan and even Chinese medicines; Ayurveda has survived

till date. In fact, as herbal medicines and Homeopathy are getting popular during recent

times, Ayurveda is also getting recognition, all over the world, as one of the most important

branches of medicine. Its success and popularity is largely because of the fact that it is

generally believed that it is capable of giving total and holistic treatment for various disease

by going to their fundamental and root causes.

Apart from Ayurveda, there are number of traditional medicinal systems partially or

fully based on the knowledge of the use of plants. A number of such systems became

socially and culturally significant in Traditional Asian Societies where they have been in

practiced for centuries. These systems have been able to continue even up to the present era

of modern and laboratory based medicines. Some of the important systems in India apart

from Ayurveda are Siddha, Unani, Tibetan and Folk medicine are the important systems of

medicine from India.

1.3.2 SIDDHA

Siddha is one of the oldest traditional medical systems of pre- vedic period which

tried to organize and formulize the human knowledge acquired about the plants, chemicals,

etc. and their role in curing various disease. This system became popular in southern parts of

India particularly in Tamil speaking areas. The word Siddha means achievement and those

who practiced and mastered the system of medicine were known as Siddha. Siddha also

means the experts in the skill of application of medicines. Needless to say, these

practitioners were saints whose treatment methodology largely depended on Yoga and were

strongly supported by the knowledge of plants, chemistry, and minerals etc .The system

integrated the scientific knowledge of material world and life forms (including plants) with

the principles of yoga to give a therapeutic system of treating patients. This system of

medicine is attributed to a great „Siddha Agastiyar”.

1.3.3 UNANI

Unani system of medicine believes that the body comprises of four basic elements

Earth, air, water and fire, which have different attributes such as cold, hot, wet and dry.

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Different compounds could be prepared by combining these elements and their attributes. A

disease was considered to be an imbalance in these elements and the treatment aimed in

restore this balance. Health, therefore, was considered as the state of equilibrium of various

elements and attributes of the body. Most of the drugs used were of plant origin though

drugs were also made with the composition of minerals and animal body parts. The

treatments could be according to one or a combination of one or more of the following

therapies:

1. Ilajbil Tadbeer (Regimenal)

2. Ilajbi Ghiza (Dietotherapy)

3. Ilajbil Dava (Pharmacotherapy)

4. Ilajbil Yad (Surgery)

This system of medicine evolved in Greece and was founded by the great

philosopher and physician „Hippocrates‟ in the fifth century BC. Since he was the first

Unani physician and initiated a systematic medicinal understanding and education, he is also

known as the father of modern medicine i.e. Allopathy. The Unani medicine was first

brought to India by Arabs in 1351 AD. Zia Mohd Masood Rasheed Zangi was the first

Hakeem in India and the system soon became acceptable to masses. At present it is one of

the established and trusted systems of medicine in India.

1.3.4 TIBETAN

Tibetan medicine is a traditional system of medicine, which has been practiced for

over 2500 years. It is the science and philosophy that provides a holistic approach to the

total health care. The basic principles are enumerated in a systematic and logical frame work

based on the understanding of the body and its relationship with the environment. It is based

on the Buddhist philosophy of humanity, karma and ethics. Tibetan medical theory states

that the universe is made up of five protoelements sa (Earth), Chu (Water), me (Fire),

rLung(Wind), and Nam mhha (Space).

1.4 OTHER SYSTEMS OF MEDICINE

These systems include Traditional Chinese medicine (TCM), Homeopathy and

Modern system of medicine or Allopathy.

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1.4.1 TRADITIONAL CHINESE MEDICINE (TCM)

This is an ancient branch of medicine and the herbal tradition, a part of it evolved

separately from Chinese folk medicine. It arose from the ideas recorded between 200 BC

and 100 AD in the Yellow Emperor‟s Classic of internal Medicine [3]. This text is based on

keen observations of nature and contains the concepts fundamental to TCM such as that of

yin and yang and that of the five elements (wu xing) along with the concept of the effect of

nature on health. The former believes that everything in nature, including the human body,

has two opposite properties referred to as yin and yang. The latter is based on five elements

viz., wood, fire, earth, metal and water each of which keeps getting converted into the next

in a perpetual way. These elements or phases in turn have other relevant influences on

human body and mind.

The TCM practitioners look for disharmony in the functioning body systems which

cause illness. This disharmony is the expression of imbalance between yin and yang traits.

Reading of pulse and tongue are regarded as important diagnostic methods. Generally

mixtures are used to treat specific illnesses and these preparations are available over the

counter. The 1977 Encyclopedia of TCM Substances lists 5,757 entries, a majority of which

are herbs. The text “The Divine Husbandman‟s Classic that listed 252 herbs is a leap in

terms of knowledge from the first century AD, when TCM was founded. Today it is treated

at par with western medicine in China where various Universities and Institutions carry out

research and development works in this field.

1.4.2 HOMOEOPATHY

Founded by the German physician Samuel Hanhemann (1755-1843), this relatively

recent branch of medicine also uses a large number of plant based medicines. It is unique as

it uses very dilute concentrations of herbal extracts to treat diseases. According to this

concept the substances that cause symptoms can also provide cure. The inherent law holds

that a substance, which induces a certain symptom (e.g. ipecac for inducing nausea), may be

used to relieve that symptom when given in very dilute dose- so dilute that the extract may

not even be detectable by routine scientific analysis. Remedies like treating malaria using

Cinchona bark are the gains of modern allopathic medicine from homeopathy.

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1.4.3 ALLOPATHY

Allopathy system of medicine creates a new system, in addition, to the short term

cure of ailment meaning thereby the cure of an aliment gives rise to new system of ailment.

According to Brittanica 1981 [7], antibiotics mean the medicines which are harmful for life.

The extent to which the diagnosis, of ailment and principles, are concerned to modern

medical science, desire to be commended but the treatment, part of the modern medicine

does not cure the aliment freely and detrimentally, it creates side effects. Now the time has

come that we should know the root causes of the ailments and that particular root cause be

eliminated first. The modern treatment therapy be reviewed and herbal drugs be promoted

because of the vast field of medicinal plants invite us to use the naturopathy and the natural

drugs. The call of present time is that the proven Indian System of Medicine may be

revitalized by encouraging herbal system of Medicine which motivates us to live with nature

through the extremely large members of the plant kingdom.

1.5 HISTORY OF MODERN MEDICINES AND ITS CONFLUENCE WITH

TRADITIONAL HERBAL MEDICINES

In ancient times, a disease was believed to be caused due to possession of Patient‟s

body or soul by evil spirits. Treatment for this was prescribed by the “Shaman” (medicine

man or woman) who was more of a „tantric‟ magic healer than a physician. To induce

hallucinogenic effect, he/she would use fungi such as ayahuasca (Banisteriopsis caapi) and

fly agaricus (Amanita muscaria). However, there were instances where the “shaman” used

plant parts as medicines for treating wounds and fevers. Even earlier works of Ayurveda

had elements of the prevailing magico religious concepts related to medication. This has

been referred as „grahas‟, and „bhuta vidya‟ [3].

With the advancement of modern medicine, the traditional knowledge was regarded

as superstitions and was grossly neglected. However, even under such circumstances, the

traditional practitioners have kept these traditions alive and these systems are practiced till

today.

As modern medicine is often considered to reduce immunity and cause side effects,

increasing number of people are turning to herbal medicines for cure. Even the modern

science appreciates herbal treatments for total health concepts (body as well as the mind),

negligible side effects and enhancement of natural immunity. As a result, today, we find

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many plant-based modern medicines. There are around 21 indispensable mainstream plant

based drugs used in the treatment of cancer, heart diseases and chronic illness; aspirin,

quinine, reserpine, digoxin, disogenin and taxol are just few examples of such drugs. It is

important to recall that a major change that continued along side the development of herbal

medicine was the form in which the medicines were prepared. To begin with, the plants

were used as crude drugs in which their parts were used as whole, then came the era of using

active principles such as extracts and solutions. This was followed by the use of pure active

principle (e.g. morphine as medicine and as direct quinine) and later by synthetic drugs. It is

not surprising that, modern medicines received many of its clues from the traditional

systems of medicine, e.g. the bhui-amalki (Phyllanthus urinaria) is traditionally used in the

treatment of Peelia(Jaundice), while modern medicine has patented a drug for Hepataitis B

from the same plant.

We do not possess complete knowledge of the real medicinal wealth which the floral

diversity contains. It is more tragic that we would never know the medicinal wealth which

we have lost permanently by way of extinction of many plant species. For example, an

extract from the leaves of plant Periwinkle (Catharanthus roseus) has been found during

1950s to have a number of alkaloids which possess the treatment of Hodgkin‟s diseases

(Cancerous disease causing enlargement of lymph nodes, liver and Spleen) which used to be

a terminal disease prior to 1950s. We can only imagine, that, had this plant been extinct

before its medicinal use was discovered we would have had no way to realize the real value

of this loss.

The ethno-botanical practices have played a great role in preserving the knowledge

of the medicinal value of plants till the human civilization developed the knowledge to a

stage when they could put such plants to laboratory examination and verification of the

claims. The ethno-botanical practices have even been instrumental in the conservation and

spread of a number of medicinal plants till the modern science discovered that they actually

had the medicinal properties they were known for. We all know of the traditional medical

systems of India, China, Egypt, Babylon etc; Even the Neanderthal people used plants as

medicines. Centuries ago the Peruvian Indians treated, malaria a fatal disease, by the

extracts of the bark of the Cinchona trees. During 1639, the knowledge of this cure reached

Europe and thereafter became a popular medicine in the name of “Peruvian Powder”.

Subsequently, quinine was extracted from cinchona bark in 1820, as the active ingredient

and was made commercially available by 1823. This remained the principal treatment for

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malaria for the next 100 years till similar compounds were chemically synthesized. Today,

we may be using synthesized substitutes of natural quinine. However, this has been inspired

and facilitated by the wisdom of the ancient man which was instrumental in the preservation

and spread of this knowledge much before the modern science confirmed that it was indeed

for the treatment of malaria. This indicates the undisputed significance of documenting

traditional wisdom through ethanomedicinal studies. The following Table 1.1 lists 50 drugs

discovered from ethanomedicinal leads.

Table 1.1: Fifty Drugs Discovered From Ethnobotanical Leads [3]

S. No. Drug Medical use Plant Sources

(1) (2) (3) (4)

1. 1. Ajmaline Heart arrhythmia Rauvolfia serpentina

2. 2. Aspirin Analgesic, inflammation Spiraea ulmaria

3. 3. Atropine Opthalmology Atropa belladonna

4. 4. Benzoin Oral disinfectant Styrax tonkinensis

5. 5. Caffeine Stimulant Camellia sinensis

6. 6. Camphor Rheumatic pain Cinnamomum camphora

7. 7. Cascara Laxative Rhamnus purshiana

8. 8. Cocaine Ophtalmic, anesthetic Erythroxylum coca

9. 9. Codeine Analgesic, antitussive Papaver somniferum

10. Colchicine Gout Colchicum autumnale

11. Demecolcine Leukemia, lymphomata Colchicum autumnale

12. Discoumarol Thrombosis Melilotus officinalis

13. Digoxin Arterial fibrillation Digitalis purpurea

14. Digitoxin Arterial fibrillation Digitalis purpurea

15. Emetine Amoebic dysentery Cephaelis ipecachuanha

16. Ephedrine Bronchodilator Ephedra sinica

17. Eugenol Toothache Syzygium aromaticum

18. Gallotanins Hemorrhoid

suppository

Hamamelis virginiana

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S. No. Drug Medical use Plant Sources

(1) (2) (3) (4)

19. Hyoscyamine Anticholinergic Hyoscyamus niger

20. Ipecac Emetic Cephaelis ipecachuanha

21. Ipratropium Bronchodilator Hyoscyamus niger

22. Morphine Analgesic Papaver somniferum

23. Noscapine Antitussive Papaver somniferum

24. Papain Attenuate mucous Carica papaya

25. Papaverine Antispasmodic Papaver somniferum

26. Physostigmine Glaucoma Physostigma venenosum

27. Picrotoxin Barbiturate antidote Anamirta cocculus

28. Pilocarpine Glaucoma Pilocarpus jaborandi

29. Podophyllotoxin Condylomata

acuminata

Podophyllum hexandrum

30. Proscillaridin Cardiac malfunction Drimia maritime

31. Protoveratrine Hypertension Veratrum album

32. Pseudoephedrine Rhinitis Ephedra gerardiana

33. Psoralen Vitiligo Psoralea corylifolia

34. Quinidine Cardiac arrhythmia Cinchona pubescens

35. Quinine Malaria prophylaxis Cinchona pubescens

36. Rescinnanmine Hypertension Rauvolfia serpentina

37. Rescerpine Hypertension Rauvolfia serpentina

38. Sennoside A, B Laxative Cassia angustifolia

39. Scopolamine Motion sickness Datura stramonium

40. Serpentine Hypertension Rauvolfia serpentina

41. Stigmasterol Steroidal precursor Physostigma venenosum

42. Strophanthin Congestive heart failure Strophanthus gratus

43. Teniposide Bladder neoplasms Podophyllum peltatum

44. THC Antiemetic Cannabis sativa

45. Theophylline Diuretic, asthma Camellia sinensis

46. Toxiferine Surgery; relaxant Strychnos guianensis

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S. No. Drug Medical use Plant Sources

(1) (2) (3) (4)

47. Tubocurarine Muscle relaxant Chondrodendron

tomentosum

48. Vinblastine Hodgkin‟s disease Catharanthus roseus

49. Vincristine Paediatric leukemia Catharanthus roseus

50. Xanthotoxin Vitiligo Ammi majus

It is interesting to note that even today more than 70% of India health care needs are

catered by traditional systems of medicines [3]. The very survival and health of many

communities is dependent upon these herbs as they don‟t have access to the modern

medicines. It is believed that about 35000-70000 plants ranging from lichens to trees have

been used for medicinal purpose across the globe [3]. The Indian system of medicine used

more than 8000 species of medicinal plants singly or in combination with other plants.

Table 1.2: Various Systems of Traditional Medicines [3]

A number of important medicinal plants known for their therapeutic values have

become rare and endangered while some of them are nearly extinct because of

indiscriminate exploitation and persistent biotic interference. Moreover, in most of the cases,

collection of medicinal plants is destructive in nature and is done, for roots,bark, tubers, and

whole plants, even before the flowering, fruiting and maturity stage of the plants. This

Various

Systems

Ayurveda Folk Homeo

pathy

Modern Siddha Tibetan Unani

Ayurveda 2351 900 189 80 1028 341 880

Folk 900 5137 164 86 971 235 573

Homeo 189 164 506 100 167 77 173

Modern 80 86 100 204 65 25 75

Siddha 1028 971 167 65 1785 277 641

Tibetan 341 235 77 25 277 350 275

Unani 880 573 173 75 641 275 979

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causes reduction in regeneration potential of the medicinal plants. Himalayas possess a rich,

profuse and varied flora mainly due to the varied climatic and diverse ecological conditions.

The Garhwal and Kumaon Himalayas have about 116 plant species as endemic and are

considered as national heritage [8].

^^fgeoku ~ vkS” k/k& Hkwfeuka Js”Be a~ AA**¼pjd ½

Maharishi Charak has also ascribed the Himalayas as the abode of superior

medicinal materials(Translation from Hindi script) [9]. Floristically, it falls under the North-

west Himalayan biogeographic zone and it is full with floral diversity comparable to any

other Himalayan regions in the country with approximately 4,000 species of flowering plant

having great medicinal, aromatic and aesthetic value. The important species of Himalayan

region which are also described in various ancient scriptures, mythological epics and Vedas

are, Myrabolans (Terminalia bellerica, Emblica officinalis and Terminalia chebula),

Rauvolfia serpentina ,Tephrosia purpurea, Tinospora cordifolia, Gymnema sylvestre,

Creteava nurvala, species of Solanum genus ,Bacopa monnieri, Asparagus racemosus,

Berberis aristata, Uraria picta ,Stereospurmum sauveolens, Desmodium gangeticum,

Zanthoxylum armatum, Boerhaavia diffusa, Achyranthes aspera, Azadirachta indica,

Justicia adhatoda, Cinnamomum tamala, Vitex negundo, Nyctanthes arbortris-tis,Berginia

ciliata, Dactylorhiza hatagirea, Habenaria intermedia, Fritillaria roylei, Aconitum

heterophyllum , Podophyllum hexandrum, Lilium polyphyllum, Rubia cordifolia, Rheum

emodi, Picrorhiza kurrooa, Gentiana kurroo,Valeriana wallichii, Nardostachys jatamansi,

Taxus baccata, Swertia chirayita, Dioscorea deltoidea, Saussurea lappa, Ephedra

gerardiana, etc.

Medicinal plants have been known for millennia and are highly esteemed all over the

world as a rich source of therapeutic agents for the prevention of diseases and ailments [10].

Recently there has been a shift in universal trend from synthetic to herbal medicine, which

can be said to be the “Return to the Nature”. Herbal Medicine is defined as the branch of

science in which plant based formulations are used to treat diseases. In the early twentieth

century herbal medicines were one of the prime healthcare systems, since antibiotics or

analgesics had not been discovered. With the advent of allopathic system of medicine,

herbal medicine gradually lost its popularity amongst people, which is based on the fast

therapeutic actions of synthetic drugs [11].

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According to World Health Organization (WHO) over 80% of the world population

relies largely on traditional systems of plant based medicines, to meet their primary health

care and other needs of society. As a result, medicinal plant and herbal preparations enjoy

great potential for internal growth and export.

Plants present viable solution for modern medicines in the following four ways:

1. They are used as direct medicinal sources.

2. They serve as a raw material base for elaboration of more complex semi-synthetic

chemical compounds.

3. The chemical structure derived from phyto constituents can be used as models for

new synthetic compounds.

4. Plants can be used as taxonomic markers for discovery of new therapeutic

compounds [4].

The therapeutic utilization of medicinal plants is generally done by making their

decoctions, infusions, fluid extracts, tinctures, pilular (semisolid) darken or powdered

extracts. The purposes of standardized extraction procedures for crude drugs are to attain the

therapeutically desired portion and to eliminate the inert material by treatment with a

selective solvent known as menstrum. Thus, standardization of extraction procedures

contributes significantly to the final quality of the herbal drug [12]. Phytochemical

constituents are the basic source for the establishment of several pharmaceutical industries.

1.6 PROBLEM STATEMENT

The Himalayan region is a largest, highest and most populous mountain chain in the

world and is home to hundreds of plant species with potent medicinal and aromatic

properties as evidenced by ancient as well as modern literature. Plants form the main

ingredients of medicines in traditional systems of healing and have been the source of

inspiration for discovery of several major pharmaceutical drugs. Around 100 plant species

have contributed significantly to the manufacture of modern drugs. The use of medicinal

plants is increasing worldwide, related to the persistence, pharmaceutical applications and

sometimes expansion of traditional medicine. This revival of interest in plant-derived drugs

is mainly due to the current widespread belief that “green medicine” is safe and more

dependable than the costly synthetic drugs, many of which have adverse side effects [14].

There is a growing interest in correlating phytochemical constituents of a plant with its

pharmacological activity [15].

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The human body requires a number of minerals in different quantities and the

deficiency of some or any of the minerals results in certain physical disabilities in human

beings. There is a need to supplement these minerals from some organic source. The

sustained supply of the organic source requires the uniform and known quantities, it

becomes imperative that we resort to the chemical analysis of the available plant materials

from different habitats and select the superior one for propagation and conservation. The

impact of deficiency of different minerals is given in Table-1.3.

Table 1.3: Impact of Deficiency of Different Minerals[13]

S. No. Elements Significance Deficiency

1 Lithium (Li) Strengthening the immune

system

Depression,

Reproductive Failure,

Rages & Fits, and

Infertility

2 Molybdenum

(Mo)

Supports bone growth and

strengthening of the teeth

Gout, Hepatitis C,

Multiple Sclerosis,

Obesity, Parasites

3 Chromium (Cr)

Important in

carbohydrate metabolism

Learning Disability,

Anxiety, Learning

Disability,Negative

Nitrogen Balance

4 Nickel (Ni) Stabilize nucleic acids Dermatitis, Anemia,

Depressed Oxidative

Ability of Liver

5 Cobalt (Co)

Integral part of Vitamin

B12.

Pernicious

Anemia,Digestive

Disorders, Nerve

Damage, Slow Growth

Rate

6 Copper (Cu)

Most important blood

antioxidants and helps the

cell membranes remain

healthy.

Alopecia (Hair Loss),

High Blood

Cholesterol, Liver

Cirrhosis, Arthritis

7 Manganese

(Mn)

It is a catalyst in the

synthesis of fatty acids,

cholesterol and

mucopolysaccharides.

Hearing

Loss,Shortened Long

Bones, Hypogylocemia,

Asthma

8

Zinc (Zn)

To fight disease and to

protect the immune

system

Anemia, Lethargy,

Loss of Sense of Smell

,Malabsorption

Memory Loss

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S. No. Elements Significance Deficiency

10 Sulfur (S)

Sulfur is important for

cellular respiration, sulfur

performs a number of

functions in enzyme

reactions and protein

synthesis

Depression, Brittle

Nails ,Brittle Hair,

Memory Loss,

Arthritis

11 Phosphorus (P)

Phosphorus is an essential

part of nucleoproteins,

which are responsible for

cell division and

reproduction.

Bone Pain, Alopecia

(Hair Loss), Weight

Loss, Fatigue

12 Magnesium

(Mg)

Magnesium is involved in

activating enzymes

necessary for the

metabolism of

carbohydrates and amino

acids.

Confusion,

Depression,

Hyperactivity,

Hypertension

13 Calcium (Ca)

Calcium in cooperation

with phosphorus to build

and maintain bones and

teeth

Rickets, Tooth Decay,

High Blood Pressure

14 Iron (Fe)

It is essential for the

oxidation of fatty acids

Aneamia, Brittle Nails,

Heart Palpitation,

Constipation,

Heamoglobin

15

Potassium (K)

Protein and carbohydrate

metabolism are dependent

upon potassium

Respiratory Distress,

"Salt" Retention,

Nervousness, Glucose

Intolerance

Apart from the above, it is necessary that different pharmacological activities of the

plant need to be known for use as drugs and investigated for treatment of general ailments

that include antimicrobial, analgesic, antipyretic and antioxidant activities.

In order to obtain sustained adequate quantities of Swertia chirayita for therapeutic

uses, it is necessary to bring this species with known chemical parameters, to cultivation and

also to maintain the quality of the product selected , chemotype population can be used for

ex-situ cultivation. This certainly asks for the detailed chemical analysis of the species.

The need of the hour is to investigate the medicinal values of those plants which are

critically endangered. It is observed that Swertia chirayita plant is of valuable importance in

pharmaceutical applications but a low amount of research work has been carried out on this

plant since the general climatic conditions are not conducive for its cultivation as the species

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is highly area specific in terms of topography, soil conditions and other meteorological

attributes. Thus, determining the pharmacological activities of Swertia chirayita will help

the rural communities in the formal settlements for remaining healthy and disease free. The

main thrust area of the present research work is to explore the chemotype superiority with

presence of various important phytochemicals in the valuable wealth of Swertia chirayita as

medicinal plants for their effective utilization. With the availability of elementary

knowledge about the pharmacological activities, further studies can be carried out like

standardization of the extracts, quantification of active principles and determination of

physico-chemical properties etc, and thus these scientific investigations may be utilized to

develop drugs for the developing the cure of many diseases.

1.7 JUSTIFICATION OF THE STUDY

Though the studies of chemical constituents have not been evidenced in various

medicinal systems, but it is justified to believe that earlier people had real knowledge of

chemical and therapeutic activity of different medicinal plants and therefore, Rasayans were

prepared from medicinal plant for curing of various diseases. The Rasaynas (compounds or

mixture) had definite proportion of specific medicinal plants indicating that the older

generation used different specific plant for the delivery of specific chemicals under the

present classification of medicinal plant. Three main types of classifications are recognized

viz genotype, phenotype and chemotype. This development of recognition of chemotype

medicinal plant exhibits the importance of chemical constituents of medicinal plants. The

present study is a follow up of finding chemotypes of medicinal plant species under scrutiny.

The various aspects of chemical analysis have been taken into consideration in the present

research work.

India had been the leader of therapeutic field through the use of medicinal plants.

The Ayurveda, Siddha, Unani, Tibetan, traditional systems of medicine all of which have

evolved in the Indian sub continent. This knowledge was passed on to China through Tibet.

Russia, Indonesia, West Germany, Hungry, China and Japan are now leading the medicinal

plant market through various successful researches on medicinal plant. India remained under

the British colonial rule and its intellectual genius started depending upon the Western

World, this had lead to relegate the importance of Ayurveda and Herbal resources

temporarily for a short span of time. The side effects of synthesized vaccines and strong

antibiotic, radiation therapy and so called health promoting vitamins and hormone have

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forced the intellectuals to come to the conclusion that if there are any harmless and

invigorating medicines, than they are only in the herbal medicines found in nature.

The Indian System of Medicine is a system to develop active constituents, of

medicinal plants for therapeutic use to enhance economic growth to support the GDP of the

country.

The Indian System of Medicine rests with the conviction of representable species.

which either substitute or is used as an alternate to already known efficient medicinal plants.

The major ailment like diabetes type II, weakness of liver can be attended to with one very

important critically endangered [16] species Swertia chirayita.

From the study of various literature and documents, it has been observed that Swertia

chirayita is called Chiretta and with this local name other plant specially like Andographis

paniculata or Kalmegh widely replaces Swertia chirayita in many drug formulations by drug

manufacturers. It is important to note that the basic trait of Swertia chirayita is Sheet

(Cooling effect) and Andographic paniculata is Ushna (Hot effect). A plant with Hot

attribute cannot replace the plant with Cool attribute but in practice Swertia chirayita is

being substituted by Andographic paniculata in many pharmaceutical parameters, thereby

degenerating and impoverishing the efficiency of known medicinal properties of Swertia

chirayita It is normally resorted to because of the deficient availability of Swertia chirayita.

The literary review reveals that plants contains various minerals. Investigation for

the presence of minerals in the Swertia chirayita is justified on the ground, in case a number

of minerals are found in it, and then assay can be used as a mineral supplement material.

Most of the literature available speaks on very small population of Swertia chirayita so

much so it has been declared critically endangered [16]. Therefore it has become imperative

that the best available quality plant in terms of chemicals present to be selected for further

propagation extension and ex-situ conservation. For this purpose the main chemical

constituents (Chemotype) Amarogentin needs to be analyzed. To understand the largest

applicability of Swertia chirayita investigation of pharmacological activities such as

antimicrobial, analgesic, antipyretic and antioxidant are needed to be done and this analysis

to be justified. The above recommended tests are been taken into consideration and as major

investigating tools to elucidate the utility of Swertia chirayita for various ailments like fever,

action on microbes, used as tonic and employed in other diseases. Vis a vis the chemicals

present in the plant species is further, it as a universal tonic for the protection of liver.

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Since Swertia chirayita (Roxb. ex Fleming) H. Karst is classed as critically

endangered species and its population is diminishing day by day, it becomes important to

increase the availability of plant material through by ex situ conservation or cultivation.

There is a wide difference in the consistency of chemical constituents of medicinal plant

species of in different populations. Scientifically the quality attribute of any plant for

reproduction can be phenotype, ecotype and chemo type for the drug manufacturing and

pharmaceutical uses. Chemo-type attribute is preferred, because drugs become efficient due

to the presence of certain active principle constituent whose properties and uses are known.

Kala (2009) [17] has done a comparison of 10 (ten) populations of Swertia chirayita

in Garhwal Himalaya for quantification of amarogentin. The present study deals with the

investigation of various pharmaceutical properties of this plant so that it serves as a standard

for ex situ cultivation and production of plant material in large or commercial scale.

1.8 SWERTIA CHIRAYITA

India is home to a great variety of ethnomedically important plant species, and is

ranked 6thamong 12 mega diversity countries of the world [18]. Uttarakhand is one of the

states of India which is known for its exquisite unique and magnanimous diversity in terms

of flora and fauna and also its rich traditional plant based ethnomedical knowledge. Swertia

chirayita (Roxb. ex Fleming) H. Karst. is one among the 32 highly prioritized medicinal

herbs from the rich biodiversity of Uttarakhand as identified by National Medicinal Plant

Board, Government of India [18] . The plant Swertia chirayita (Roxb. ex Fleming) H.

Karst. has been listed in Red Data Book, due to which many conservation programmes

came into existence, these includes in-situ, ex-situ/in-vitro mode of conservation.

Phytochemical analysis as well as molecular facet of medicinal plant Swertia chirayita has

been and are being explored in many research institutes globally.

The taxonomic position of the plant is as follows:

Order: Gentianales

Family: Gentianaceae

Tribe: Gentianeae

Subtribe: Swertiinae

Genus: Swertia

Species: chirayita

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Swertia chirayita (Roxb. ex Fleming) H. Karst. is also mentioned in the literature as

Swertia chirata ,Buch.-Ham.;Ophelia chirata Griesb; Agathotes chirayita Don.;Gentiana

chirayita Roxburgh. [19-22]. It is known by an array of names in India, suggesting its

widespread use .The vernacular names of the plant in different languages are given in Table

1.4.

Table 1.4: List of Vernacular Names of Swertia chirayita 22]

Language Common name

Sanskrit Kirata, Kirataka, Bhunimba,

Kiratatiktaka

Assamese Chirata

Bengali Chirata

Gujrati Kariyatu, Kariyatun

English Chiretta

Hindi Chirayata

Kannada Nilavembu, Chirata Kaddi, Chirayat

Gujrati Kariyatu, Kariyatun

Tamil Nilavembu

Telugu Nelavemu.

Urdu Chiraita

Punjabi chiretta, Chiraita

Malayalam Nelaveppu, Kirayathu, Nilamakanjiram

Marathi Kiraita, Kaduchiraita

Oriya Chireita

Kashmiri Lose, Chiraita

Burma. Sekhagi

Patna, Cherayata

Arab,Farsi Qasabuzzarirah

It is one of the oldest medicinal herbs of traditional system of Indian

Medicine. In Vedas and Samhitas, it has been mentioned as “Kirattika” which means the

bitter plant of Kiratas (an outcast race in mountains in the North India). It is also called

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„Anarya-tikta‟the bitter plant of the non-Aryans which indicates that Kirata tribals are native

of this country. In short, it is also called „Kirat‟ or „Kirayata‟ .The popular name „Chirayata‟

or „Chiretta‟ appears to be the modified word of „Kirayata‟.

1.8.1 DISTRIBUTION

Swertia chirayita is reported to naturally occur in Europe and Asia from Western

Himalayas to Eastern Himalayas including Afghanistan, Pakistan. Though, there are

indications that this plant species, which occurred commonly, in the forest, is now rarely

found in the high altitudes of the Indian Himalayan region, it has also become scarce in

other states of its general occurrence. Distribution of chirayita is not uniform; it depends

upon the altitude and slope of the area. It generally prefers to grow on northern aspectss. It

can also be grown in sub- temperate regions between 1500 m. amsl and 2100 m. amsl

altitudes [23]. It grows scantily in south facing slope between 1500 m and 3000 m while on

the northern aspects (facing slope), it descends below 1500 m. amsl on shady sites. The

plant is a native to temperate Himalayas, found at an altitude of 1200-3000 m. amsl from

Kashmir to Bhutan, and in the Khasi Hills at 1200-1500 m. amsl [21,22].

1.8.2 FLORISTIC DESCRIPTION OF SWERITA CHIRAYITA (Roxb. ex Fleming) H.

Karst.

The various ancient Indian therapeutic authors and practitioners have described the

plant on the basis of its dravya gunas (Therapeutic characterstics). The Gentianaceae family

is an important family, well recognized by the western pharmacopoeias. The Swertia

chirayita (Roxb. ex Fleming) H. Karst is an important species of this family. According to

Fleming, Chirayita possesses stomachic, tonic, febrifuge and anti-diarrhoetic virtues which

are ascribed to gentian and in a greater degree than they are generally found in it in the state

in which it comes from Europe. Experiments carried out in the School of Tropical medicine,

Calcutta for the chemical composition of Swertia chirayita also show that it can effectively

replace the gentian of British Pharmacopoeia. The percentage of bitter principle was found

to vary from 1.42 to 1.52. This compares favuorably with the bitter principle existing in

Gentiana kurroo. There are several spurious kinds of chiretta in the market as well. Swertia

angustifolia, Swertia decussata, Swertia corymbosa, and Swertia pulchella are used in the

indigenous medicine in South India. Some of these are not bitter at all and are, therefore,

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devoid of the therapeutic activity. True chiretta, viz: Swertia chirayita has now been

recognized in the British and the United States Pharmacopoeias [24].

Hakims also use this drug extensively [24]. In Unani system of medicine Swertia

chirayita is treated as “Hot 2, dry20, tonic to heart, liver and eyes, resolvent, drying,

astringent, liquefying, balgham, cough, scanty urine, melancholia, dropsy, sciatica, skin

diseases [24]. Floristic Swertia chirayita (Roxb. ex Fleming) H. Karst is a robust plant 60 to

180 centimeters in length, branching, teret except near top, stout, branching towards top,

stem round ; quadrangular towards top, green. Leaves 70-90 X 35-40 mm broadly

lanceolate, sessile, elliptic acute, 5- 7- nerved (Plate 1.1). Flowers tetramerous,calyx

smaller than corolla, oblong, tip acute, green, 1- nerved, 5-6 mm in size. Corolla is

gamopetalous, greenish petals which are violet in center (Plate 1.2). Bear two glands on each

petal each gland is a depression, which is bright green inside. Margin of the depression is

covered by long purple hair which converges to form a summit. Its Androecium has 4-

versatile filaments and anthers purple in colour, filament base slightly dilated. The

description of Dhanvantari Nighantu and Prakash are important references.

fdjkrdks jls frDrks∙uq”.k’khrk sy?k qLrFkk A

‘ysa”ekfiRRlz’kk sQfrZdklr’̀.kkTokigk AA ¼/k-fu-½

fdjkr%lkjdks:{k%’khrfLrdks y?k qA

lfUuikrTojÜokldQfiRrkL++=ngkuqr~ A

dkl‘kk s/kd”̀BTojoz.kd f̀eiz.k qr~ AA¼Hkk0 iz0½

The tap root has yellowish pith with no smell. Fruit is a capsule bearing numerous

minute seeds (Plate 1.3 and Plate1.4). The plant mostly grows in open, moist places and

forest openings. The plant can be grown in a variety of soils with sandy loam rich in carbon

and humus (Plate 1.5). Chirayita prefers to grow in acidic soil condition with pH of 4.7 to

5.5 [24]. It is also found in open ground and recent slash burnt forests.

Flowering: July - October Fruiting: August – December

The ethno botanical utilization of this species is well known, it is used in its crude

form for treatment against fever, treatment against scorpion sting, as a tonic for liver and

heart. Its utility as an antidiabetic agent has also been recognized. In Ayurveda the action of

Swertia chirayita is bitter tonic, stomachic, febrifuge and anthelmintic. An infusion of the

drug is generally employed, but it forms part of many compound preparations.

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Swertia chirayita (Roxb. ex Fleming) H. Karst has been an important medicinal plant

for ages. Its antihelmintic, hypoglycemic and antipyretic properties are attributed to

amarogentin, swerchirin, swertiamerin and other active principles of the herb. The wide

spread use of Swertia chirayita in traditional medicine reflects its pharmacological

importance. However, existing populations of Swertia chirayita are diminishing due to

various biotic factors. Thus plant has been classed in critical endangered by CAMP 2003

[16].

During the preliminary surveys of the Swertia chirayita from the known site, it was

found that most of the sites had very poor or non-significant population to become

representative site of Swertia chirayita expect for two sites, where the population of Swertia

chirayita were significant and possessed good vigour. These sites were selected for the

further investigations.

1.9 OBJECTIVES OF THE STUDY

The present study is entitled

“Chemical Investigation of Swertia chirayita for Resourceful Application in

Pharmaceutical Industry”

The objectives of the present study are

1. Comparative analysis of Physico-chemical properties from the two different sites in

Swertia chirayita.

2. Comparative elemental analysis of Swertia chirayita in dried plant of two different

sites.

3. Comparitive quantification analysis of amarogentin in Swertia chirayita from two

different sites.

4. Phytochemical analysis of Swertia chirayita in different solvents.

5. Pharmacological activity of Swertia chirayita.

Antimicrobial Activity

Antioxidant Capacity

Analgesic Activity

Antipyretic Activity

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1. 10 ORGANIZATION OF THE THESIS

This thesis is devoted to find the medicinal and therapeutical value of Swertia chirayita

plant. The thesis is divided into five chapters including the present chapter of introduction.

Chapter II presents the review of literature on the different aspects of the plant Swertia

chirayita relevant to the research problem.

Chapter III contains the description of study sites, research methodology used for the

objective no.1, 2 & 3, along with the all results and the discussion there on. It also includes

information related to the collection of the plant material and its identification. The study

sites are Chakrata (CK) and Kaddukhal (KK) of Garhwal region in Uttarakhand.The

objectives dealt with are:

1. Comparative analysis Physico-chemical properties from two different sites (Chakrata

and Kaddukhal).

2. Comparative elemental analysis of Swertia chirayita in plant specimen from the two

different (Chakrata and Kaddukhal).

3. Comparison of quantity of amarogentin in Swertia chirayita from two different site

(Chakrata and Kaddukhal).

The elemental analyses are carried out by ICPMS technique, the quantification of

active constituents was performed by HPLC.

Chapter IV deals the description of objective no. 4 and 5, it covers qualitative

analysis of phytochemicals in different solvents and different pharmacological activities of

plant Swertia chirayita including result and discussion. Agar well diffusion method was

used for antimicrobial activity, antioxidant capacity by free radical scavenging method

respectively. Hot plate and Tail Flick method were used for analgesic activity. Antipyretic

was also studied in this Chapter by Brewer‟s yeast induced hyperpyrexia method.

Chapter V presents the conclusion and the scope for further research work.

References-The references used to support the various statements have been

presented in this section.

Annexure-The different annexures, which have been referred in the main body of

the thesis have been appended as annexures.

………………..