HEAL WITH HERBS

SHARADINI DAHANUKAR&

AVUIT HAZRA

•National Institute of Science Communication

Dr K.S. Krishnan MargNew Delhi 110012

Heal with Herbs

Sharadini Dahanukar

& AvUit Hazra

©Nationallnstitute of Science Communication(CSIR)

First Edition: November 1995

Reprinted: July 2001

ISBN: 81-7236-111-4

Editor-in-Chief

Editor

Cover Design

Colour Plates

Production

Dr G.P Phondke

Parvinder S. Chawla

Anand Kandalgaonkar

Sushila Vohra

K.B. Nagpal, S. Bhushan, Anjali Sehgal,

Gulab singh and R. Neena

Designed, printed and published byNational Institute of Science Communication (CSIR)Dr. K.S. Krishnan Marg, New Delhi-110 012

Price: Rs.50/-

Preface

The histories of medicine and botany are inextricably linked fromthe earliest ventures in both fields. Although synthetic pharmaceu­ticals now dominate the drug scene, medicinal plants continue tohold a place in international health care. Around one quarter ofprescription drugs are still extracted or derived from plants. Thebend towards re.,exploration of plant wealth in technologicallyadvanced countries like Germany, Japan and France has not onlyimproved the quality and quantity of natural products research buthas also led to increased interest in such products all overthe world.Herbal prod ucts of increasing sophistication are infiltrati ng the massmarket. There is rethinking on the need to integrate 'western' and'traditional' remedies. Awareness of the importance of naturalheritage and biodiversity is growing.

In this scenario, a strong link of communication needs to beestablished from the research worker to the public for the benefitof the community at large. In 'Heal with Herbs', we have attemptedto cater to this need by giving an interesting account of plantderiveddrugs. If our readers are able to share the joy and the fascinationwhich carried l,lS through, our purpose will have been well served.

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Contents

Our green friends

The journey of curare

4

No time to sleep over morphin(!

6

The cinchona romance

8

The story of foxglove

15

The secrets of cannabis

17

It's in your cuppa

19

The fu ngus on rye

21

The magic of mushrooms

24

The wonder of willow bark

26

Herbal hopes against cancer

28

Babies versus plants

34

Blood pressure: Ups and down

37

On sugar and fat

40

Life saving poisons

43

Botanic tools

46

Keeping stress at bay

53

The glaucoma link

56

Old plants, new remedies

59

Diet and drugs

61

Green aids to formulation

63

The herbal melting pot

68

Beware of plants!

76

The futu re of pharmacognosy

78

List of illustrations/colour platesPlant

Amanita muscaris

Amanita phal/oides

Amanita pantherina

Arachis hypogaea; Seeds of A. hypogaea (Inset)

Artemisia annua

Asparagus racemosus; Root of A. racemosus (Inset).

Atropa bel/adona

Azadirachta indica; close-up of leaves (Inset)

Berberis arista

Cannabis sativa

Carica papaya

Cinchona officina/is; Bark of C. officinalis

C1aviceps putpurea

Coca leaves

Coffea arabica

Cola nuts

Commiphora muku/; Guggul gum (Inset)

Colchicum autumna/e

Curcuma /onga; Rhizomes of C. /onga (Inset)

Datura stramonium; Datura Seed (Inset)

Digita/is purpurea

Dioscorea mexicana; Tuber of D. mexicana (Inset)

Emb/ica Officinalis; Close-up of leaves (Inset)

Erythrina; Close-up of flowers (Inset)

Ficus benga/ensis

Ga/erina pa/udosa

GossYPium herbaceum

Hyoscyamus niger

Page No.29

29

29

70

II69

51

49

72

II71

10

30

II12

12

50

70

31

51

II32

69

9

50

29

32

52

Mentha spp.

Nicotiana tobacco; Close-up of flowers (Inset)

Panax gienseng; Close-up of root (Inset)

Papaver somniferum; Capsules of P.somniferum (Inset)

Podophyllum peltatum

Rauwolfia serpentina

Salix alba

Senecio spp

Strychnos nux vomica

Taxus baccata

Thea sinensis

Thymus spp.

Triticum vulgare

Veratrum viride

Vinca major

Withania somnifera

71

72

52

10

30

49

30

72

9

30

12

72

71

49

31

69

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Our planet Earth is more than 4.6 billion years old. The

first algae made their appearance 3.0 billion years agoand modern man, Homo sapiens, evolved only over thepast hundred thousand years or so. Diseases are as old

as mankind and it is

not surprising thatman, thE;rational ani-mal that he is, wouldfirst turn to plants insearch of remedies.And nature, with theaccumulated wis­dom of three billion

years of evolution,did not disappointhim. Pharmacognosy- the study of plants as sources of drugs - is, therefore, one of theoldest disciplines.

Though as old as human civilization, pharmacognosy remainedmore an art than a science for several millenia. It was left to the

tribal medicine man, the witch doctor or.the faith healer to gathernis own herbs, prepare pills and potions from them and put themto use. The knowledge gained through a lifetime of such efforts waspassed on by word of mouth to others of his own creed.

The fi rstwritten records of med icinal plants and thei r usesdo notappear till the clay tablets used by Sumerian and Babylonianphysicians around 3000 Be. Chinese records of medicinal plantsare more than 4000 years old, the Pen Tsao or the Great Herbalhaving been compiled during the reign of Emperor Shen Nung. TheEbers papyrus, dated to circa 1500 BC mentions several herbspopular with the ancient Egyptians. The first undisputed referenceto poppy juice is in the writings of Theophrastus in the third centuryBe. He is credited with having founded the science of botany. He

HEAL WITH HERBS

also authored a number of manuscripts dealing with plants - theHistoria P/antarum being the most famous. Charaka Samhita, themagnum opus of Indian Ayurvedic texts, was authored by the greatIndian physician in the first century AD, though references tomedicinal plants appear in the much older Vedas, particularly theAtharvaveda.

The realization that there is something more subtle to theworki ngs of med ici nal plants than the crude extract of the root, the

infusion of the crushed leaves or the powdered bark themselves,dawned only with the advent of chemistry in the late 18th century.Chemists gradually started isolati ng pure substances and opined thatcertain active molecules underline the therapeutic actions of plants.Compound after compound came to be identified. In the 20thcentury researchers began deciphering their molecular structuresand from hereon there was no looking back.

Scientists are a peculiar breed. They will stop at nothing. Givethem a bucketful of sludge from a sewage outfall off the coast ofSardinia and they will discover cephalosporin producing fungi inthem. Tell them that cattle feeding on spoiled sweet clover arebleeding abnormally and they will show that it is only due tocoumarin anticoagulants. They will even not shirk from distillingthousands of litres of human urine to recover microgram quantitiesof metabolites. Not surprisingly, such gifted men cannot remaincontent with plants. They turn to bacteria, marine invertebrates,fishes, amphibians, quadrupeds and the human body itself on thelookout for new drugs. They happily elucidate drug structures,modify molecules to make them more specific and lesstoxic in theiraction and then go on to synthesize altogether new molecules.Physiologists, microbiologists, immunologists, geneticists, molecularand cell biologists have all joined the race. Technologically ad­vanced man is beginning to custom design drugs for his needs.

So, are plants relevant today? The answer is still an emphaticyes. Consider the following facts:

1. WHO estimates that 80% of the global population still relieson plant based medicines for primary health care and a large sectionof this almost entirely so.

2

OUR GREEN FRI~NDS

2. Even in the most developed countries 25% oh:urrently prescr­

ibed medicines were first identified in plants.

3. Plants have been an economical source of 'feedstock' mole­

cules that can be transformed into drugs. Thus, development of

steroidal oral contraceptives has been possible largely because of

the plentiful supplies from the processing of steroidal componentsof plants such as Yams (Diosr:Aea spp) and Sisals (Agave spp).

4. Even if herbal molecules cannot be directly utilized, they can

serve as models for designing more effective drugs, a fact elegantlydemonstrated by the peripheral neuromuscular blockers.

5. Technological advances can reveal novel compounds and

activities in plant remedies which had eluded science so far. Thus

the immunomodulating activities of many plants, several of themnative to the I nd ian sU'bconti nent, are bei ng appreciated only withthe discovery of interferons, cytokines and other immunomod­ulators.

6. Many natural compounds have not found therapeutic appli­

cations but have nevertheless, made it possible to understand themechanics of drugaction and advance the science of pharmacology.This is the case with bicuculine, an alkaloid from some members of

Fumariaceae, which is still the most specific antagonist at the

receptors for gamma amino butyric acid (CABA).

7. Finally, the potential for discovering new drugs from plants isfar from exhausted. There are an estimated 250,000 species of

flowering plants worldwide and less than 10% of them have been

investigated for their medicinal properties.

These reflections are sobering and the grim realities of environ­mental destruction, loss of biodiversity and species extinction

should strike a note of urgency in the study of plants for their

pharmacological value. Otherwise, we may lose, without evenknowing so, the bounties that mother nature has in store for us.

3

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If an Amazonian Indian were to be brought from his native hot

and humid jungles to the air-conditioned ambience of amodern operating theatre and informed that modern medi­cine needs to pay homage to the ancient wisdom of his tribe,

he would bestunned. He would

not see the singularlink - a link that lies

at the tip of his arrowwhich he has likelyleft behind!

For long the Indi­ans living along thegreat South Ameri­can river valleys haveused arrow poisons derived from plants in hunting. These poisonsparalyzed the game before killing it. Preparation of such arrowpoisons was a closely guarded secret known only to the tribalpriest-cum-medicine man. In the late 16th century, samples of thesepreparations, called curare, reached Europe through the efforts ofearly explorers to that continent on the other side of the Atlantic.Alexander von Humboldt did pioneering work in identifying thebotanical sources of curare which are Strychnos toxifero, Chondroden­

dron tomentosum and related species. In 1932 curare received itsfirst clinical trial when West employed purified extracts in treatingp~tients with tetanus and spastic disorders. King established thestructure of tubocurarine in 1935. Seven years later Griffith andJohnson reported the use of curare alkaloids in procuring skeletalmuscle relaxation in general anaesthesia.

Further developments followed. Curariform compounds wereidentified in Asian, African and Australian species of Strychnos ­(curiously they turned out to be tertiary strychnine like compoundsin contrast to the quaternary tubocurarine) - and other genera like

THE JOURNEY OF CURARE

B-erythroidine from Erythrina. The natural alkaloids provided mo­lecular templates for the development of semisynthetic derivativeslike alcuronium. Gallamine was described as a purely syntheticsubstitute by Bovet and his team in 1949. The site of action wasestablished as the nicotinic cholinergic receptors at the neuromus­cular junction. Exploration of structure-activity relationship of theplant alkaloids led to the methonium compounds like hex­amethonium and decamethonium. The former was found to be

devoid of neuromuscular blocking activity but is an efficient gan­glion blocking agent.

Modern surgery would be unthinkable without the peripheralneuromuscular blockers to achieve a satisfactory degree of skeletalmuscle relaxation. The only other way to procure this is dangerouslevels of general anaesthesia. From the Amazonian jungle to theoperating theatre, it has been a long and arduous journey. But inthe end it was worth it.

5

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In1806 a young German apothecary's assistant, 5erturner,

isolated a pure substance from opium which he called mor­phine after Morpheus, the Greek God of dreams. This discov­ery had been long in coming. Opium, the juice of the unripe

seed capsules of thepoppy plant (Papaver

somniferum), wasknown for its hyp­notic and analgesicvalue probably fromthe beginning of civi­lization. The 5umeri­

ans, Egyptians,Indians, Greeks, Ar­abs - all had used

opium. Even Paracel-sus, the eccentric 16th century genius who pioneeredchemotherapeutics in Europe, appreciated the value of laudanum(opium tincture). So did patients in pain and, in a perverse manner,the addicts who smoked away their lives in opium dens acrossEurope and the Orient. 5erturner's discovery opened the floodgatesof research into opium. More than 20 alkaloids were isolated instages though none more potent in central action than morphine.By 1960s the existence of opioid receptors in the body had beenpostu lated and confi rmed.

A pertinent question that troubled the fastidious minds of re­searchers is why there should be binding sites for morphine and itscongeners in the body? Surely nature did not intend these receptorsto be there just because some day somebody would stumble uponpoppy juice and decide to try it out. This was too illogical. So begana systematic search for endogenous Iigands which culminated in themid-1970s with the discovery of the endogenous opioid peptides

by Hughes, Kosterlitz, Goldstein and others. This was a remarkable

NO TIME TO SLEEP OVER MORPHINE

feat of scientific detection. Within a few years three distinct familiesof endogenous opioid peptides: the endorphins, enkephalins anddynorphins, and other multiple categories of opioid receptors, hadcome to light.

The next obvious question related to the functions of these endo­genous opioids. It is clear that they are widely distributed andsubserve diverse roles. Presumably, they constitute a system thatregulates nociception, mood, pituitary secretion, gut motility andotherfunctions. ~-endorphin is primarily localized to two endocrineglands namely, the pituitary and the hypothalamus. It hasa relativelylong half-life and when injected intracerebrally produces analgesiawith 20 - 40 times greater potency than morphine. Enkephalins anddynorphins have a wider distribution, a shorter half-life and pre­sumably act as neurotransmitters. They appear to influence painperception at spinal and supraspinal levels. Naloxone, a pure opioidantagonist can block acupuncture, placebo and stress inducedanalgesia, suggesting the involvement of the opioid peptides inthese responses. Moreover, they exhibit varying affinity for thedifferent receptors.

Research continues at a furious pace - from the molecularlaboratories where opioid receptor genes are being cloned to thepatient's bedside where clinicians are trying to help terminal cancerpatients in pain preserve the last vestiges of dignity. Opioid conge­ners of all hues are coming up and more opioid receptors are in theoffing. You may say that a grain of morphia will put anybody to sleepbut you have underestimated the addicts. There are two kinds ofopioid addicts - the literal kind who are tolerant enough to digestyour grain without so much as the drooping of an eyelid, and thefigurative kind who keep the midnight oil burning over the whys,hows and wherefores of morphine, long after the rest of the worldhas gone to sleep. Hats off to the latter!

7

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A 30 year old man was admitted to hospital in a confused

state with poor general condition and a history of highfever and headaches of about a fortnight's duration.Examination revealed altered sensorium, anaemia, mild

icterus, low bloodpressure and a twofinger splenomegaly.On close questioningthe patient's relationsstated that initially thefever occured in ir­

regular peaks accom­panied by chills andrigor. Peripheral thickand thin blood filmswere drawn immedi-

ately and sent to the laboratory. The report came short and terse­ring forms of malaria parasite found; extensive parasitaemia. Withcerebral malaria on his hands, the wise resident doctor took no

chance. As the hospital was in a known chloroquine resistantmalaria endemic area and the patient had already taken pills whichcould have been chloroquine, he started him on quinine infusion.Recovery was rapid and uneventful.

Our resident doctor made use of a remedy that began its sagalong ago in the jungles of Peru. Quinine is the principal alkaloid ofthe bark of the Ci nchona tree (Cinchona officinalis, Cinchona succirubra

and several other species) which is native to tropical South America.Calancha, an observant missionary, first wrote about its use by thePeruvian natives in his Order's chronicles in 1633. Nobody inEurope paid much attention to this Peruvian bark till a Jesuit fatherbrought itto Rome - then a notorious malarial spot. Itcured amongothers, Cou ntessAnna del Cinchon, wife of the Viceroy of Peru andthe aged Cardinal de Lugo of Rome. The latter was so impressed

Strychnos nux vomica(Pages 4,46)

Erythrina (Page 5)

9

F~uitsof S. nux vomica

Papaver somniferum (Page 6)

Capsules of Psomniferum

Cinchona officina lis (Pages 8,26)

Cinchona bark

10

Digitalis purpurea (Page 15)

Artemisia annua (Page 13)

Cannabis sativa (Page 17)Coca leaves (Page 18)

11

Thea sinensis (Page 19) (;()ffAA Ambica (Pag~ 19)

Cola nuts (Page 19)

12

THE CINCHONA ROMANCE\r/

that he issued official directions for its use. Soon the Jesuits were

shipping it regularly to Europe and pilgrims began to take home littlepackets of Jesuits; bark for friends and relatives suffering frommalaria. Slowly, but surely, Europe fell in love with Cinchona. Itbecame as essential as gunpowder to the colonialists. Plantationswere established by enterpreneurs at home and in the colonies.Finally, in 1820 quinine was isolated from Cinchona bark by Pelletierand Caventou in France. Cinchona was tried as a remedy for feverof all kinds. So also was quinine. Its use as a specific antimalarialnaturally had to await the discovery of the malaria parasite. Thesynthetic antimalarials which came of Ehrlich's earlierwork on dyes,were not put to clinical use till Japanese invasion of the South EastAsian and Pacific islands in 1942 cut off the source of Cinchona

supplies for the Allied troops during World War II.

Malaria remains the scourge of the tropical world. About 56 %

of the. world's population lives in malaria endemic zones. Despitethe availability of a number of synthetic antimalarials quinine hasnot outlived its usefulness. In view of its toxicity it is not usedroutinely now but held as a reserve drug. With the climbingincidence of chloroquine resistant and multidrug resistantfalciparummalaria, this reserve has become even more valuable. Other anti­malarials have come through the screening of synthetic compoundsstructurally related to quinine, like mefloquine. Researchers havefound new uses for quinine such as in nocturnal leg cramps. Andthe Cinchona alkaloids have turned out to be powerful antiarrhyth­mics. Physicians had been noting that malarial patients who hadatrial fibrillation were occasionally cured of this when given q ui­nine. Wenckebach in 1914 reported on this. Following his lead Freyand others studied cinchonine, quinine and quinidine in atrialfibrillation and other arrythmias and found quinidine, the opticalisomer of quinine, to be the most effective.

But plants have -'not exhausted their potential for antimalarialdrugs ..Artemisinin from the Sweet wormwood (Artemisia annual is anew antimalarial. It is a potent and rapidly acting blood schizo­nticide reported to be particularly useful in cerebral malaria. It isactive against chloroquine resistant strains of Plasmodium falciparum

and is also less toxic than chloroquine. But the problem of recru­

descence remains. ,?f the semisynthetic derivatives being tested,

13

HEAL WITH HERBS

artemether and sodium artesurate appear most promising. Believeit or not, Artemisia is the same herb Qing hao su, the Chinese havebeen using for various maladies from as far back as at least 168 BC!

14

'I'III~S'I'CtllY()I~ I~()][(.I~()'TI~

Once upon a time, there lived in Shropshire, England, an

old woman who was suffering from dropsy. WilliamWithering, a general practitioner who lived nearby, wascalled upon to attend to this sick dame. Withering found

that he could not domuch for the bloated

old lady and herweak heart and so,

comforting the pa­tient and her relativesas best as he could,left in gloomy spirits.But some days laterhe was greatly sur-prised to be informedthat the lady still livedand what's more, had improved! Withering, an astute physicianwith some botanical knowledge up his sleeves, paid another visitand made enquiries as to what she had taken. This led him to adecoction of foxglove leaves and his classic paper of 1785 titled 'Anaccount of the foxglove and some of its medicirial uses: withpractical remarks on dropsy and other diseases.'

Foxglove refers to some 20 - 30 species of herbaceous plants ofthe genus Digitalis that are native to Europe and the Medite­rraneans. The active principles of these plants are now known to beglycosides with positive inotropic action such as digitoxin from thePurple foxglove (Digitalis purpurea) and digoxin from the Yellowfoxglove (DigitalIs lanata). The story of the foxglove does not beginwith Withering and the old lady. It begins earlier, scattered refer­ences to foxglove being found in old European herbals, mainly asan emetic. Plants with similar active compounds like Squill (Urgineamaritima) had been knpwn to the ancient Egyptians and the Romans

who employed its fleshy bulb as diuretic, emetic and rat poison.

HEAL WITH HERBS

Many other plants have been shown to contain cardiac glycosides- one of the most potent being ouabain from Strophanthus gratus.

Though Withering scarcely appreciated the cardiotonic activity ofDigitalis, regarding it primarily as a diuretic, he accurately describedits principal side effects including its cardiotoxicity. It was left toFerriar to ascribe to Digitalis a primary action on the heart in 1799.Digitoxin was isolated from the crude drug in 1869 in France.Digitalis became popular and eventually physicians started using itso indiscriminately, 'ignoring Withering's original warnings, thattoxicity became widespread and Digitalis fell temporarily into disre­pute. It was revived again early in this century.

Digitalis continues to be used to this day but we have come along way since Withering. Today we know accurately thepharmacological properties of Digitalis and its pharmacokineticprofile, have identified the receptors with which it interacts, havenarrowed down its us.especifically to the treatment of congestiveheart failure and the control of ventricular rate in atrial tachyar­rythmias and are tackling its toxicity with certain fragments ofantibodies. Even, similar glycosides have been isolated from theamphibian skin.

But the tale, as they say, is never finished. Indeed we are nowembarking on a fresh new chapter with the discovery of an endog­enous digoxin like compound in human urine. It appears to be asteroid with molecular weight less than 500. It occurs particularlyin the adrenal glands, binds to the enzyme called Na +/K+ - ATPase(ouabain receptors), interacts with anti-digoxin antibodies and thelevel of this compound isshown to increase in the plasma of patientswith essential hypertension and chronic renal insufficiency. Onlytime can tell whether this chapter will have a happy ending.

16/

rl'III~SI~(~111~rl'S()I~(~1'NN1'IIIS

The Indian hemp, Cannabis sativa is an erect aromatic

annual herb that originated in Central Asia and now growswidely throughout northern temperate zones. A tall cane­like variety is raised for the production of hemp fibre. The

female plant of ashort branchier vari-

ety is prized for theresin ofthe floweringtops, leaves, seedsand stems. The resincontains hallucino­

genic substances.

Cannabis has longbeen known as an

euphoriant, sedativeand analgesic. A Chi-nese herbal mentions it around 2700 Be. Today it is the darling ofdrug abusers. Cannabis. has many other names. Hashish and charasrefer to the pure resin. Ganja, bhang, marijuana ('Mary Jane'),dagga, kif, pot, weed and grass refer to various crude preparationsof the plant or the drug. It is chewed, smoked, brewed into teas andbaked into cakes. But Cannabis has been a disappointment tomodern medicine. With the exception of one compound, Tetrahy­drocannabinol, and its derivatives as powerful antiemetics, it hasnot fou nd many uses for the plant.

Why then bother about Cannabis? If you are a pleasure seeker, aphysician treating such a pleasure seeker, a social worker, a lawenforcer or someone in the government, then it is understandable.After all Cannabis is the most abused substance in the world. But

what more could be there for pharmacologists? The answer isreminiscent ofthe tale of morphine. Unlike opium, Cannabis is oneof the few substances that produce psychological effects withoutestablishing physical dependence. Pleasure seekers suffer no great

HEAL WITH HERBS

physical discomfort upon withdrawal from the drug. But like opium,researchers have stumbled upon receptors for active componentsof Cannabis in the central nervous system (CNS) and are nowpondering upon why these should be there. Is it because the humanbody produces its own cannabinoids? If so, what for? If we are ableto answer these questions then perhaps we shall beable to find newdrugs and explain the process of psychological dependence better.

With benzodiazepines the tale is twisting the other way round.So far the anxiolytic, sedative, hypnotic, anticonvulsant, musclere"laxant benzodiazepines are all synthetic compounds. They havebee n found to act at receptors linked to the activity of the inhibitorycentral neurotransmitter gamma-amino butyric acid (CABA). Pre­sumably, benzodiazepine-like molecules with GABA-ergic activitywill someday be isolated from plants.

Cocaine comes from the leaves of Erythroxylon coca, a bush nativeto the Andes. In small doses cocaine has a pronounced stimulantaction on the CNS producing a pleasurable state of well beingassociated with relief from fatigue, increased alertness and physicalstrength and a reduction of hunger. In larger doses it is an intoxicant,producing excitement, hallucinations and convulsions. The Incaswere well acquainted with the euphoriant and hallucinogenicactions of cocaine. Even today the natives who dwell high in theAndes chew coca leaves for increased strength and endurance.Cocaine snuff, 'snow' and 'crack' are abused for their euphoriantaction. Cocaine was also the first local anaesthetic to find clinical

use. Would it be too farfetched to expectthat it may yet be possibleto tailor cocaine and related alkaloid molecules so as to separatetheir wonderful euphoriant action from their abuse potential andprovide a sorely needed fatigue relieving drug.

18

I'I"S IN V(ttJll(~tJI)I)l'

The popularity of caffeine containing beverages can be

blamed on their antisoporofic and stimulant actions thatelevate mood, reduce fatigue and improve work capacity.This popularity has been handed down to us through

centuries. Legendcredits the discoveryof coffee to the priorof an Arabian con-

vent. Shepherds toldhim that goats thathad eaten the berries

of the coffee plantgamboled andfrisked about all nightinstead of sleeping.The astute prior,mindful of the long nights of prayer he had to endure, instructedthe goatherds to pick the berries so that he might brew refreshingdrinks from them. Legend apart, caffeine, theophylline and theo­bromine are three closely related stimulant alkaloids that occur inplants widely dispersed geographically. It is more likely that prehis­toric man discovered the principle xanthine containing plants andbrewed drinks from them.

Today at least half the world's population consumes tea which is

prepared from the cured leaves of Thea sinensis. Tea is said to be the

national pastime of Britain and it is India's major foreign exchange

earner. An average cup of tea contains about 30 mg of caffeine.

Coffee is richer giving about 85 mg per cup. It is extracted from thefruits of Coffea arabica and Coffea robusta. Coco from the seeds of

Theobromacacao gives 250 mgtheobromine and about 5 mgcatfeine

in every cup. Cola flavoured drinks contain considerable amounts

of caffeine, partly because of the extracts of cola nuts (Cola acuminata

HEAL WITH HERBS

- the Guru nut chewed by the natives of Sudan) and partly becauseof the pure caffeine that is added during their preparation.

Caffeine, theophylline and theobromine are methylated xan­thine alkaloids. They have diverse pharmacological actions ­central nervous system stimulation, myocardial stimulation, im­proved skeletal muscle function, relaxation of smooth musclesspecially that of the bronchii, modest di uresis and increased gastricacid and pepsin secretion. In order to explain these diverse effectstheir cellular mechanisms of action are being studied intensivelyand this has helped to shed new Iighton the molecular basis of drugaction. Clinically, theophylline and its derivatives remain one of themainstays of bronchial asthma and chronic obstructive pulmonarydisease therapy. Both caffeine and theophylline are being employedto counteract prolonged apnoea in preterm babies. Caffeine isavailable as a stimulant as such and is also incorporated in manypreparations to relieve migraine and other types of headache. Andthe potential for new uses is not exhausted.

So the next time you hold your morning cup of tea or similarbeverages, pause awhile and decide whether you still want to goon taking the drugs. We bet you wouldn't care!

20.

rl'III~1~'JNf.'JSf)N IIYI~

The Middle Ages were difficult times for Europe. Science

was in the doldrums. The iron hand of the Church dictated

the daily lives of all and sundry. The Black Death (plague)descended upon an unsuspecting populace and within

months wiped away an estimated third of it. The sailors who sailedwith Christopher Co­lumbus to the New

World brought backa new scourge, syphi­lis, with them. Con­stant battles and wars

kept everybodyguessing as to whowas ruling whom.And to add to all the

woes, the grainfieldsof Europe began to be contaminated by a poisonous fungus C1aviceps

purpurea, the product of which is ergot.

Consumption of ergot contaminated rye can lead to poisoningcharacterised by peripheral vasospasm and subsequent dry gan­

grene. It has done so through centuries. As early as 600 BC anAssyrian tablet referred to the 'noxious pustule in the ear of grain'.

But extensive ergot poisoning began to appear in Europe in the

middle ages. Strange epidemics were described in which the limbs

gradually dried, blackened like charcoal and in severe cases fell offwithout loss of blood. There were accompanying agonising burningsensations. Expectant mothers suffered abortions. Convulsions oc­

cured from time to time. Artists depicted the misery in paintings and

wood carvings. Affected limbs were said to be consumed by the

Holy Fire or St. Anthony's Fire in honour of the saint, a journey to

whose shrine brought relief, presumably because of the change toa healthier diet.

HEAL WITH HERBS

Ergot was known as an obstetrical herb long before it was recog­nised as the cause of the Holy Fire. One ofthe sacred books of theParseesrefers to noxious grains that caused women to miscarry anddie in chilbirth. European midwives used it as an abortifacient anduterotonic agent for a long time before it came to the notice ofphysicians. In 1808 John Stearns published an 'Account of PulvusParturiens, a Remedy for Quickening Childbirth' and thereby for­

mally introduced ergot into medicine. Desgranges had used ergotearlier but he did not publish his observations till 1818.

Ergot is a treasure trove to pharmacologists. It contains an arrayof bioactive substances - ergot alkaloids, acetylcholine, histamine,tyramine and other amines, sterols and so on. Beginning with thefirst isolation of an active substance, ergotoxin (now known to be amixture of four different ergot alkaloids) in 1906 by Berger, Carr,Dale and others, discoveries have continued. Ergotamine was ob­tained by Stoll in 1920. Another compound, ergometrine camethrough Moir in 1932. Two series of optically active isomericalkaloids came to be isolated from ergot. The laevo isomers arepharmacologically active and are the naturally occuring forms. Theinactive dextro isomers result from chemical manipulation. A hostof semisynthetic derivatives of ergot alkaloids have been synthesisedand several are of therapeutic interest such as bromocriptine (2­bromo-ergocryptine), methylergometrine (lysergic acid hydroxy­butylamide) and methysergide (l-methyl-me~hylergometrine).Lisuride, lergotrile and metergoline represent non-lysergic acidsynthetic conge ners of the am ine ergot al kaloids. The ergot al kaloidsand their derivatives have diverse actions - agonist, partial agonist

and antagonistic influences at adrenergic, dopaminergic and trypta­minergic receptors. The net action depends on the balance of thedifferent interactions in individual organs. Ergotamine can terminateacute attacks of migraine. Ergometrine and methylergometrine areemployed as powerful uterotonic agents. Bromocriptine has multi­ple usesincludingthe treatment of prolactinomas and Parkinsonism.Codergocrine is said to improve senile dementia. Lysergic aciddiethylamide (LSD), an amine alkaloid, was vividly described as apsychedelic by Hoffman in 1943. It is one of the most powerfulhallucinogens known, active in microgram quantities, and absorb­able through the skin. Curiously its effect can recur episodically for

22

THE FUNGUS ON RYE

several years (flashback phenomenon) after the last exposure, high­lighting the mystery of the human brain.

The development of ergot alkaloids, determination of theirpharmacological action and evaluation of their therapeutic poten.tial is an important and unfinished chapter of pharmacology. Theergot alkaloids have numerous and complex actions. Though thislimits their clinical use somewhat, the treasure trove is not empty.New discoveries will continue to be made. New uses continue to

be found. And itall began with the poisonous fungus t~at renderedthe rye inedible.

23

rl'III~)ll'(.I(~()If

IIIJSII11()()IIS

Have you seen a mushroom in its natural surroundings?

You don't need to be a poet or a botanist to appreciateits beauty, especially if it is a colourful toadstool. The

curious umbrella shape, the soft spongy feel, the splashof vivid colours and

that peculiar aroma,

all lend splendour tothe rotting logs

surrounding itand re­

mind you once againof nature's expertcraftmanship. Pick

the mushroom up

carefully, turn it over,

and run your fingersalong the delicate

fronds beneath the cap - but for heaven's sake don't taste it! We

assure you, eating a wild mushroom can be a most unpleasantexpenence.

There are some 30,000 species of large mushrooms and only a

small percentage of them are known to be poisonous. But thepoisons can be deadly. Ironically, the most poisonous species re­

semble some of the most prized edible varieties. Some mushrooms

that are poisonous when fresh become edible when cooked, dried,

salted or treateJ;i..in some other way. Others remain poisonous~

defyi ng all such manipu.I.a.~i_o~ Mushrooms ofthe same genera maypossess quite distincttoxins and the same species may show varying

toxicity from one set of local ecological conditions to the next. Some

people may get poisoned by eating mushroorl!s that apparently donot affect others. A confusing state of affairs indeed.

Pharmacologists too are captivated by mushrooms - though thisis due to a vested interest in their toxins. Historically, muscarine wasthe first cholinomimetic alkaloid to be isolated, from the fly agaric,

THE MAGIC OF MUSHROOMS

Amanita muscaria, by Oswald Schmiedeberg. Schmiedeberg and

Koppe published the first careful pharmacological study of mus­carine in 1869. Muscarine subsequently came to playa vital role in

the development of neurotrasmitter theory beginning with Dale'sclassical observations in 1914 that choline esters produce responsesthat mimic that of either muscarine or nicotine. Muscarine is the

active principle of many poisonous mushrooms such as the PantherIl)ushroom, Amanita pantherina; Jack 0' lantern fungus, C1itocybe

illudens and /nocybe patouillardi. The toxicity of Amanita phalloides

(Death cap), Amanita verna (Deadly agaric), Amanita bisporigea (De­

stroying angel), various species of Ga/erina, are however not due toalkaloids but due to an entirely different group of potent toxins­

the amatoxins and phallotoxins - which are cyclic peptides inhib­

iting messenger RNA synthesis. The False morel, He/vella escu/enta

is interesting because it produces the hepatotoxin gyromitrin, the

toxicity of which is variable between individuals and is lethal inabout 15% cases. The Ink cap, Coprinus atramentarius contains

coprine which can be metabolized to disulfiram, which, as weknow, can take all the pleasure out of a discreet peg or two of

alcohol. Many mushrooms are noted for their powerful hallucino­

genic effects particulary the magic mushrooms (various species ofPsi/ocybe, Conocybe, Strop haria etc.) from Mexico. They contain

psilocin and psilocybin as their principle psychotogenic compo­nents.

So, while mushrooms continue to capture hearts as evidenced

by the current mushrooming in the popularity oftheir consumption,researchers conti nue to study them in the hope of devisi ng antidotes

at least, if not for obtaining new remedies and research tools. It isfortunate that this be so, as the mushroom magic can so easily turnblack at a moment's indiscretion.

25

rl'DI~"Tf)NI)I~11()I~"TII..I..() "T

111l111'

The willow is a common sight in the countryside of the

temperate regions of the world. They are majestic treesgrowing to heights of 18 - 20 m with long narrow leavesand male and female catkins bloomingon separate plants.

There are over 70 differnt species - White willow (Salixalba), Blackwillow (Salix nigra)and Brittle willow

(Salix fragilis) bei ngamong the largest.The leaves, fruits,bark of the willowtree contain a bitter

glycoside salicin,which on being takeninternally, is metabo-lized by the body tosalicylic acid/an effective analgesic-antipyretic- antiinflammatoryagent. The ancients knew the valu2 of these plant products and theyhave been mentioned by Hippocrates.

It was 'in the mid-18th century that willow bark began to bewidely used in Europe for antipyresis as a cheap substitute to theimported Cinchona bark. It was considered worthwhile to try thewillow as it grew in marshy places where fevers abound andaccording to the 'doctrine ofsignatures', where a disease was found,there ought to be a remedy provided by benevolent nature. Fur­thermore/ Reverend Edmond Stone, who wrote a formal accountof the use of the willow bark for agues to the President of the RoyalSociety in 1763/ was impressed by its bitter taste which suggesteda resemblance to Cinchona.

Pure salicin was isolated by Leroux in 1828 and, subsequently,salicylic acid synthesized from phenol by Kolbe in 1874. Sodiumsalicylate was tried in rheumatic fever and pyrexial illnesses thefollowing year and its uricosuric action and efficacy in gout were

THE WONDER OF WILLOW BARK

discovered soon thereafter. The triumph of this drug spurred Hoff­man, a chemist with the Bayer company, to synthesize acetylsalicylicacid based on an earler work by Gerhardt. In 1899 Dresser intro­duced this compound to clinical medicine under the name ofaspirin with miraculous results. It was the first real drug for arthriticdisorders, bringing relief to countless stiff joints, and proved to bethe best antipyretic so far, short of immersing the patient in ice.

Today aspirin is a household name globally. We consume alarm­ing quantities of aspirin - well over 40,000 tons annually whichcomes to 30 standard tablets yearly for every denizen of the world.The Bayer company which first marketed aspirin made a fortuneand others followed in its footsteps. The drug has side effects butw~en used judiciously the good far outweighs the bad. Aspirin is onevery doctor's prescription at one time or the other and is alsoavailable as an over-the-counter medication in most countries. We

still do not understand its effects fully and none of its original usesis outdated. Chemists have spawned whole families of pharma­cologically similar agents, going by the collective name of N5AIDs,but aspirin remains the standard against which every new aspirantis judged. And now, to our amazement, we have rediscoveredaspirin as an antiplatelet drug which can prevent narrowed vesselsfrom clogging altogether.

So, the next time you stop to listen to the wind in the willows,exalt in the wonder of the willow bark and bow your head in

respectfu I silence.

27

III~11111'1..

II()I)I~Sllf.llINS'I'(~1'N(~1~11

Cancer! The very word conjures up dread. To physicians it

is perhaps not so much as the dread of losing yet anotherlife as the numbing disgust of repeatedly surrendering thetherapeutic battle against the disease.

Cancer is not a sin-

gle disease. It is rathera multitude of poten­tially fatal diseases,each with its own sus­

pected aetiology, riskfactor associations,

tissue specificity andnatural history. Howdoes one fight a dis­ease one does not

understand fully?Well, we have tried to cut it out (surgery), burn it out (radiotherapy),poison it out (chemotherapy) or employed any combination ofthese. And now we are trying to steal a page or two off nature'sbook by targetting modified DNA (gene therapy) or monoclonalantibodies (immunotherapy) against some cancers. The last twostrategies are still in their infancy.

Plants hold great promise of chemotherapeutic drugs to fightcancer. Have you noticed the neighbourhood periwinkle plantf Itis a hardy shrub growing wild, with brown shoots, shiny dark greenleaves and small violet flowers. Its Madagascar relative, Catharanthusroseus, has earned universal admiration by yielding the Vinca alka­loids, vincristine and vinblastine. They are powerful cytotoxic agentswhich bind to tubulin proteins, inhibit mitotic spindle formation andarrest dividing cells in metaphase. They are being used, usually aspart of combined regimes, to treat Hodgkin's and non-Hodgkin'slymphomas, lymphocytic leukaemia, Wilms tumour, neuroblas­toma, rhabdomyosarcoma, Ewing's sarcoma and carcinomas of the

Amanita ohallo(des (Page 25)

Amanita muscaris (Page 25) 29 Galerina paludosa (Page 25)

Claviceps purpurea (Page 21)Salix alba (Page 26)

Taxus baccata (Page 33)

Vinca major (Page 28)

Curcuma longa (Page 36~

31

Gossypium herbaceum (Pages 35,66)

Tuber of D. mexicana

32Dioscorea mexicana(PagEJ 35)

HERBAL HOPES AGAINST CANCER

breast, bladder and gonads. Drug designers have been quick tocatch on and produce new anticancer drugs by structure modifica­tion like vindesine (desacetyl-vinblastine-amide) and vinorelbine(5' -noranhydrovinblasti ne).

Podophyllum resin from the Mayapple plant (Podophyllum pe/­

tatum) has been folk remedy to the American Indians for generationsfor its emetic, cathartic and antihelminthic effects. We still use

podophyllum extracts for warts and Condylomata. The activeprinciple is podophyllotoxin. Two semisynthetic glycosidic deriva­tives of this principle, etoposide and teniposide, show therapeutic

activity against a range of malignancies including Hodgkin's disease,

diffuse histiocytic non-Hodgkin's lymphoma, small cell broncho­genic carcinoma and testicular cancers.

Taxo\s from the yew plants - Pacific yew (Taxus brevifolia) and

European yew (Taxus baccata) - are a new class of cytotoxics that

inhibit de polymerization of tubulin. They are being tried out forantileukaemic and antitumour activity specially against ovariancancers. Hopefully, the high expectations will survive.

With cancer we are up against formidable odds and no weapon

in our arsenal would be superfluous in the ensuing battle. Chemicalweapons are simplerto wield and though, considering their toxicity,

they are still double-edged swords, let us be patient. There is no

shame in seeking help from our green neighbours to fightthis deadlydisease as we have done for other maladies right from the first dawnof civilization.

33

IlllIIII~S'TI~11S(JS1)I.JlN'I'S

In 1798 Thomas Robert Malthus sparked a great controversy

by concluding that 'the power of the population is infinitelygreater than the power in the earth to produce subsistence forman', ..... a 'natural inequality' that would someday loom in­

surmountable in the

way to the perfecti-bility of society.' Lessthan 200 years laterthere is no contro­

versy but a grim factstaring us in the face.The world popula­tion today stands atwell over 5 billion

and isclimbing stead-i Iy. Mankind is grow-ing but rapidly outpacing our planet's capacity to supply food,energy and other resources in the process. Mankind is propagatingitself towards extinction. What a paradox!

Progress in medicine is largely to praise or blame forthis paradox.We are trying not to let human life go cheaply. The ever growing listof vaccines, antimicrobials, antineoplastics and other drugs aremaking our prophylactic and therapeutic armamentarium strongerby the day. Mortality rates are coming down. Life expectancy isgoing up. And again, paradoxically, it is to medicine that we haveturned to deliver us out of the dilemma. Antifertility drugs are theneed of the hour and we have some effective ones already with

promise of more to come from plants.

Throughout the centuries midwives have used herbs to procureabortion. Abortifacient herbs contain irritant and toxic principleswhich on being appplied to the uterus or taken internally stimulatevigorous uterine contractions that expell the conceptus. But a muchbetter way of regulating fertility is to prevent conception in the first

BABIES VERSUS PLANTS

place. This can be done by using judicious combinations of thefemale sex steroids - oestrogens and progestins - a combinationknown to women around the world as 'the pill'. And developmentof the pill would not have been possible without raw materials fromplants.

The discovery of oestrogen and progesterone in the 1920s and1930s brewed great interest in the medical profession as it raisedthe possibility of controlling a wide range of gynaecological condi­tions and disorders. But experimental and clinical applications ofthese hormones was hampered by the problem of availability. Itproved to be extremely expensive and complicated to extract themfrom the obvious animal sources. The ovaries of 50,000 cows

yielded a paltry 20 mg of progesterone to one researcher in 1934.Nothing could be more frustating. Deliverance came at last throughRussell Marker, a chemist at the Pennsylvania University who haddedicated himself to the study of steroids. Marker became con­vinced that steroid hormones could be produced simply andcheaply by starting with plants that were known to contain steroidprecursors and subjecting them to chemical transformation. Hebegan looking at hundreds of plants and found the Mexican yam(Dioscorea mexicana) to be the most promising. After intensive studiesMarker concluded that it was possible to convert one of its constitu­ents namely diosgenin, to progesterone, by an efficient five stepprocess thatcould readily be adapted for massproduction. A furtherthree step process could then transform it to the male hormone,testosterone. Not surprisingly, his discovery was so good that itprovoked scepticism. Markerwalked outon both the University andthe pharmaceutical firm which was funding him, went to Mexicocity, set up his own laboratory in a little rented cottage and after awhile coolly announced the production of four and half pounds ofprogesterone from the yam - then worth 80 dollars per gram. Hewent on to set up a small firm Syntex S. A. to market the hormonesand forced prices to drop worldwide.

The search for male antifertility agents has been less rewardingpartly because of the difficulty in suppressing spermatogenesiscompletely without producing permanent sterility. In China, re­searchers have come up with gossypol, a phenolic compound fromcotton seed oil, extracted from species of Gossypium. It can produce

35

HEAL WITH HERBS

near aspermia and impair sperm motility. The effects are reversiblewithin several months of discontinuation. But there is the hitch ofa few trou blesome side effects.

Indian researchers too are coming up with interesting observa­tions. Saponins of Albizzia lebbeck and ethanol extracts of Randiadumetorium inhibit copper acetate induced ovulation mediatedthrough central neurohumoral mechanisms. Extracts from Aristolo­chia indica, Vitex negundo, Randia dumetorium intercept the synchro­nized dOevelopment of the fertilized ovum and the endometriumthrough their antioestrogenic activity while those from Curcumalonga, Embelia ribes, Mentha avensis render the endometrium unre­ceptive to implantation through their anti- prostaglandin effects.'Centchroman', derived from the rhizomes of Curcuma longa pro­d uces asynchrony between ovu m transport and endometrial prepa­ration for reception of the fertilized ovum without affecting thehypothalamo-pituitary-ovarian axis. It is being readied for market­ing as an oral contraceptive and needs to be taken only on a twiceweekly basis. If successful it would be a major step forward in safe,effective and user-friendly contraception.

Thus while healthy babies are- desirable, the baby boom is notproving healthy for mankind. The choice is between healthy babiesand more-babies. If the gentle promise of plant derived antifertilitydrugs comes to be realizeq, it would make the choice all the moreeasier. Our green neighbours would have once again come to ourrescue.

36

111..f)f) I)1)111~SSIJI11~:

tJI)S llNI)l)f)"TN

The force that keeps blood coursing through vessels allover

the body can be dangerous when it chronically exceeds

limits. High blood pressure or hypertension slowly but

surely wears away the resilience of the vessel walls, maki ngthem weak and frag-

ile. It is a staggeringhealth problem for

many reasons. It isvery common, its ef­

fects are widespread

and no organ isspared, it remains as­ymptomatic till late inits course and its out­

come is sometimes

devastating. More­over in 90 - 95% cases

the cause remains essentially unknown. Abrupt swings in blood

pressure are dangerous too. A sudden fall can cause fainting andlow perfusion ischaemic injury to the tissues, a sudden rise canru pture vessels in the retina or brain or cause the overburdenedheart to fail.

It is imperative therefore that hypertension, once detected, betreated. If the cause is unknown the treatment can only be directed

towards keeping the pressure within acceptable limits. This is wheredrugs come in. Antihypertensive drug therapy today is based onpotent synthetic drugs. But not so long ago, it was a plant product,

reserpine, which ushered in the era of effective antihypertensive

pharmacotherapy.

The sarpagandha plant is a climbing shrub indigenous to theIndian subcontinent. In 1703 Plumier, a French botanist, named it

Rauwolfia serpentina in honour of Leonhard Rauwolf, a 16th centurybotanist, who probably never even knew of the existence of the

HEAL WITH HERBS

plant. The snake like roots ofsarpagandha were well known in Indiaas it had been recommended in Ayurveda for the treatment ofinsomnia and insanity. Sen and Bose's report on the hypotensiveand antipsychotic effects of extracts of the root in 1931 went largelyunnoticed in the western world, except atthe Swisscompany, Ci ba,where chemists started taking a close look atthis Indian folk remedyin the late '1940s. Then in 1955, Vakil published a paper on theantihypertensive action of the plant in the prestigious British HeartJournal. Following this lead, a Massachussets heart specialist gavethe powdered root of Rauwolfia to 50 hypertensive patients and overthe next 8 months recorded a steady drop in their blood pressures.With precise timing, Ciba announced the isolation of the principleresponsible for this action - the alkaloid reserpine - and soonthey were marketing it as Serpasil.

Rauwolfia serpentina actually contai nsseveral alkaloids. Reserpineand rescinammine are ester alkaloids with the most effective anti­

hypertensive profile. Reserpine causes depletion of noradrenalinestores in peripheral sympathetic nerve terminals and depletion ofcatecholamines and serotonin in the brain, heart and many otherorgans, evincing a fall in blood pressure, bradycardia and centralnervous system depression. Because of its several side effects,notably depression and extrapyramidal reactions, reserpine is notused today except as a reserve drug for refractory cases. But it wasthe first sympatholytic agent to be discovered and is still invaluableas a research tool. Recently rauwolscine, another Rauwolfia alkaloid,has been reported to be a selective adrenergic receptor antagonist.

The hypotensive ester alkaloids from the Green hellebore (Vera­

trum viride) are no longer used clinically but have a singular mecha­nism of action. They influence the membrane of excitable cells tocause repetitive firing after a single stimulus without themselvesinitiating a response. This is due to increased sodium conductivityof the membrane. The repetitive impulses triggered, by a givenstimulus, in the afferent fibres involved in the regulation of bloodpressure, converts phasic activity to a tonic one, thereby resettingthe reflex responses to reduced levels. They also acton barorecep­tors of the carotid sinus to lower blood pressure.

While Rauwolfia and the Veratrum alkaloids lower blood pressure,another little herb, Ephedra, a favourite with the Chinese, can raise

38

BLOOD PRESSURE: UPS AND DOWN

the same. Ma huang (Ephedra sinka) has been recorded as antispas­modic and stimulant in Chinese herbals of the 16th century BC!The dried young branches of this plant and close relatives likeEphedra vulgaris, Ephedra equisetum and Ephedra gerardiana containprotoalkaloids, notably ephedrine afld pseudoephedrine. In 1887Japanese chemist Nagai isolated ephedrine. In 1920 Eli Lilly'schemist, K. K. Chen, made a close study of it and soon thereafterthe company started marketing ephedrine. The drug is a sym­pathomimetic agent which releases catecholamines at peripheralnerve terminals and also acts directly on the adrenergic receptors.It has been used as a pressor agent, particularly to counter hypo­tension during spinal anaesthesia. As a nasal decongestant it pro­vides symptomatic relief in disorders with a stuffy running nose. Itrelaxes bronchial smooth muscle with less potency but greatersustenance than adrenaline. It is also a central stimulant and a

mydriatic. In 1927 ephedrine was synthesized chemically and it isthis form which we use now. Interestingly, the hypertensive effectof ephedrine is often masked in the whole extract of the plant dueto pseudoephedrine. This goes to illustrate that whole plant reme­die~;can differ significantly in action from isolated 'pure' constitu­ents. This may be good or bad depending on the action desired.Orthodox medicine is apt to look upon this with suspicion since thenature of the interaction in the whole plant is often complex andmany of the interacting principles unknown.

39

f)N SIJf.llilllNI) I~ll'l'

.......... "

Man isa peculiar animal. Other animals eatto satisfy their

hu nger. Man eats to fill his stomach and then goes onto satisfy his tongue. But his tongue is insatiable and hereaps the consequences. Overeating brings in its trail

obesity, diabetes,hyperlipidaemiq,atherosclerosis, hy­pertension, coronaryheart disease andsuch other maladies

of the well fed phy­sique. Of courseeach of these disor­ders is multifactorial

with the aetiology notalways understood.But dietary overindulgence is a major influence.

Diabetes mellitus is an incurable frustrating disease. Its hallmark- an elevated blood sugar (glucose) level. There are different kindsof diabetes but the commoner kind occurs in obese individuals with

a tendency to overeat. The discovery of insulin by Banting and Bestin 1921 generated tremendous excitement. The resultant euphorialed many to believe that the problems of treatment and aetiologyof Diabetes mellitus had been solved. But as time passed, it becameapparent that treatment required more than simple injections ofinsulin and the aetiology was more than mere destruction of islettissue. Further, the action of the hormone was in itself complex,involving the metabolism of not only carbohydrates but also proteinand fat. Many patients also developed progressive resistance to theaction of insulin. Steady progress has been made on the insulinfront. We can now mass produce the human hormone in bacterialcell factortes using recombinant DNA technology. A multitude ofpreparations of varying pharmacokinetic profiles is available to

ON SUGAR AND FAT

choose the one best suited to an individual. The oral antidiabetics

came in the late 1950s through serendipitous observations of the

hypoglycaemic action of sulphonamides in typhoid fever by onegroup (leading to the sulfonylureas - tolbutamide was the first) and

similar action of guanidine in rats by another (leading to the

biguanides - phenformin was the first). These drugs are effective

when combined with dietary restrictions but carry side effects and

show troublesome interactions with other drugs.

So the search for antidiabetics continues and some researchers

are now taking a hard look at plants. Though a marketable plant

derived hypoglycaemic agent is not immediately forthcoming, pre­

liminary observations on some are encouraging enough to warrant

further studies, and screening programs are yielding others in

various laboratories. Thus the bitter gourd (Momordica charantia)

promotes peripheral utilization of glucose. The fresh juice of this

plant is reported to potentiate tolbutamide action and a crystalline

fraction isolated from the fruits produces hypoglycaemic effectcomparable to insulin in juvenile diabetes. Extracts of neem (Azadi­

rachta indica) exert a definite hypoglycaemic effect in animals under

controlled laboratory conditions, affecting the glycogen content of

the liver in the process. Pterocarpus marsuPiam reduces blood sugar

level and hampers glucose absorption from the gut. A flavonoid,

epicatechin, isolated from this plant, is reported to promote regen­

eration of the ~-cells of the pancreatic islets. Clinical trials have

re ported be neficial effect in maturity onset diabetes. The leaf extract

of Gymnema sylvestre can block hyperglycaemic response to adrena­

lin, corticotropin and somatotropin. Tinospora cordifolia inhibits

adrenalin induced release of glucose from the liver and promotes

insulin induced glucose uptake in the peripheral tissues. Peripheral

glucose utilization is also improved by Casearia escu/enta. The an­

tidiabetic influence of the sap of banyan (Ficus bengalensis) is asso­

ciated with its anabolic and pancreatotroph ic effects. Plant products

that increase the peripheral demand of glucose for growth and

metabolism in a manner akin to growth hormone may promote

weight gain in lean diabetics. Such products, even if they are notpotent enough to be stand alone antidiabetics, can be useful

adjuncts to insulin therapy with a hormone sparing effect.

41

HEAL WITH HERBS

While the link being hyperlipidaemia and diet is strong, thatbetween hyperlipidaemia and atherosclerosis is undisputed.Atherosclerosis is an insidiuous process but its consequences canbe devastating in the long run. Slowly and steadily the cholesteroldeposits build up as plaques on the vessel wall, clogging the lumen.This reduces perfusion and invites platelets to form a thromboticplug to cut off the blood supply altogether. The unfortunate victimis struck down with heart attack or stroke or gangrene. The best wayto deal with this, no doubt, is to reduce the dietary intake of fat,particularly animal fat which has a higher cholesterol content. Butsomething must be done when the process is already under way,and it is here we can look to plants to provide better alternatives tothe established drugs. The common vegetables Parval (Trichosanthus

dioca) and Guar (Gyamposes tetrag%ba) and some plant sterols lowerblood cholesterol by interfering with fat absorption and reducingsynthesis. Plumagin, a naphthaquinone derivative isolated fromPlumbagozey/anica lowers I-}othtotal cholesterol and LDL-cholesterolin hyperlipidaemic rabbits and even causes regression of the athero­matous deposits in the arteries. Boswellia serrata affects cholesterolbiosynthesis in the rat liver. But best of all so far, is the oleoresinfraction of the guggul plant, Commiphora muku/ (gum guggul). Thework of Satyavati and others on this plant, developing on clues fromAyurveda, has shown that the active fraction has hypolipidaemicactivity comparable to clofibrate with a more favourable H DL- toLDL-cholesterol ratio on clinical trials. It also reduces platelet adhe­siveness and stimulates fibrinolytic activity, factors which can affordadditional protection against myocardial infarction. The drug isnow being marketed in India.

Life with diabetes is not sweet and excess of fat is not flattering.If plants can provide effective antidiabetic and hypolipidaemicdrugs, mankind would be grateful. After all,itwould spare man themisery of counting calQries every time he sits down to a meal.

I..II~I~'Sil 'TINC;

I)()IS()NS

Insecticidesare ever popular with suicides. All you have to do

is to procure a bottle, write a note if you feel like it, find asecluded spot, unscrew the cap, take a lastcontemptuous lookat the world and pour the contents down your throat. The

stuff won't taste nice,it will f3robably bereeking of the solventkerosene, there

would be burning inthe throat and prob­ably vomiting as well- but these are tri­fles, not worth both­ering about whenyou aim to migrate toeternity to rest. Ifyour aim is just to frighten those who do not take you seriouslyenough, then also you will succeed provided you take the precau­tion of gulping down a nottoo large amount and choosing your spotcarefully so that you are discovered soon enough. Concernedacquaintances or strangers would rush you to hospital, doctorswould pass a tube down to wash out the stomach, cannulate yourveins to replace the fluids you would be losing through variousmucosal surfaces of the body and revive you with several ampuolesof a curious drug - atropine.

Atropine is the drug of choice for poisoning by organophosphateand carbamate insecticides, which include such well known brand

names as TIC 20 and BAYGON. Such poisoning is a commonplaceoccurence, specially in rural farming communities of our country.Accidental poisoning occurs among pesticide handlers and spray­ers. The insecticidal compound inactivates the enzyme whichterminates the action of the neurotransmitter acetylcholine after itis released from the cholinergic nerve terminals. The result is

HEAL WIT/-(HERBS

continued occupation of receptor sites by acetylcholine and sus­tained parasympathetic stimulation. Atropine acts by competingwith the endogenous neurotransmitter for occupancy of one of themajor receptor subtypes - the muscarinic receptors - therebyreversing the excessive stimulation. This mode of action is alsoreflected in the other uses of atropine, such as to procure pupillarydilatation for examination of the retina, particularly in young chil­dren, and to give rest to the intrinsic muscles of the eye in inflam­matory conditions like keratitis and iridocyclitis. Injections of thedrug can increase the rate and velocity of impulse conduction ofthe heart to counteract sinus bradycardia and heart blocks follow­ing conditions like myocardial infarction and Digitalis overdose.Atropine injections can be life saving in such situations or at leastbuy time for other therapeutic interventions. It is also the life savingantidote for the rapidly developing muscarinic type of mushroompOisoning.

Scopolamine, a close congener of atropine, shares its propertiesbutwith some interestingdifferences.ltcan prevent motion sicknessmost effectively and is now available as an adhesive patch to beapplied behind the ear before the start of the journey. Protection

from vomiting can last from several hours to a few days. Because itcan sedate and produce short term amnesia, scopolamine injectionsare used by anaesthetists to mask the unpleasantness of inductionof anaesthesia.

Both atropine and scopolamine are alkaloids occuring naturallyin plants of the Solanaceae family - Atropa bel/adona (Deadlynightshade) and Datura stramonium (Thorn apple) being majorsources of the former and Hyoscyamus niger (Henbane) and Scopolia

carniolica of the latter. And both are deadly poisons in their ownright. Preparations of the bel/adona plants, as they are called, havebeen known for ages to physicians, who employed their healingproperties and to rogues, who exploited them to nefarious ends.Indigenous Indian medicine has a long tradition of use of Datura

fruits, seeds, leaves and flowering tops. Datura fastuosa, Datura atroxand Datura metel are other varieties found in the subcontinent. It

has also been a well known stupefying poison used by bandits tostupefy and rob unwary travellers.

44

LIFE SAVING POISONS

The bel/adona alkaloids have a relatively simple structure which

has facilitated molecular juggling by the drug designers. A host of

semisynthetic congeners have come up with relative selectivity intheir actions. Some are used as mydriatics and oy'c1opegics, some

as antispasmodics, some for gastric antisecretory activity and quitea few for central anticholinergic effects. The last group constitutes

a significant adjunct for the treatment of Parkinsonism and are the

only agents effective in iatrogenic Parkinson's disease. But the purealkaloid atropine, isolated by Mein way back in 1831, remains

unsurpassed in its life saving potential. The goal of current researchis to better characterize the receptor subtypes on which the drugs

act and utilize this knowledge to tailor them for specific c1inical uses.

Long live the poisons!

45

Ilf)rl'i'NI(~rl'f)f)I~S

Despite the tremendous advances in medicine, the work­

ings of the human body and mind still abound in mys­teries. Our intellect - which distinguishes us from amere animal existence, comprises such faculties as

memory, judgment,and reasoning, whichare still largely un­fathomed. For sometime now it has been

apparent that thehigher faculties arenot abstract entitiesbut have definite

physiological basis.Exchanges of neuro-transmitter sub-

stances, modification of synaptic connections, interactions of neuralnetworks are believed to be involved in their functioning. Thegenesis of such diseases as schizophrenia, dementias, Parkinsonism

and many others is also hard to explain. To explore these intriguingphenomena a medical scientist need tools. And experience hastaught him that molecules from plants offer some of the mostinteresting exploratory possibilities.

Strychnos nux-vomica seeds contain the deadly alkaloidal poisonstrychnine. It excites the central nervous system (CNS) throwing thebody into violent convulsions while leaving the mind absolutelyunclouded. As little as 30 mg may be fatal within the span of a fewconvulsions. Strychnine has little therapeutic potential though it haslong been popular as a stimulant 'tonic' in highly diluted prepara­tions. To the pharmacologist strychnine's importance lies in itssingular mechanism of action in terms of central synaptic transmis­sion. It profoundly excites all levels of the CNS, not by stimulatingpost-synaptic neurons, but by selectively blocking presynaptic in-

BOTANIC TOOLS

hibitory pathways that normally play the major role in regulating thespread of neural excitation. Experiments with strychnine havehelped to identify the amino acid glycine as the predominantpresynaptic inhibitory neurotransmitter in the CNS. Picrotoxin, anon-nitrogenous convulsant poison from the seedsofthe EastIndianclimbing shrub, Anamirta cocculus, is also a powerful global stimulantof the CNS. However, it antagonizes the action of a different centralinhibitory neurotransmitter - gamma-amino butyric acid (CABA)- at both pre- and post-synaptic sites. Both strych!line and picrontoxin induced convulsions in animal models are used to screen

candidate antiepileptic drugs. The elucidation of CABA mediatedneurotransmission in the brain and discovery of CABAergic path­ways was greatly facilitated by experimentation with CABA agonistsand antagonists. Bicuculline, also an alkaloid, occuring in Dicentra

cucullaria and several other plants, is a selective CABA antagonistlike picrotoxin. But unlike picrotoxin it acts at the receptor sites forCABA.

Neurobiologists, inspired by the discovery of glutamic acid andaspartic acid asexcitatory neurotransmitters in the CNS, have foundmolecular probes for the characterization of the pharmacology ofexcitatory amino acids (EAA) in two plant based antihelminthicprinciples - quisqualic acid from seeds of Quisqualis chinensis,

Quisqualis indica, and Quisqualis fructus, and kainic acid from thedried red alga Digenea simplex. Both are relatively selective agonistsat the respective EAA receptor subtypes which are accordinglydesignated as quisqualate and kainate receptors. The prospect ofusing such EAAantagonists therapeutically, for instance in iscahemicinsults to the CNS and in epilepsy, is bright.

In 1899 Stillmark isolated a protein from the castor bean whichhad the unusual ability to agglutinate red blood cells (RBC). Lateron such proteins, capable of clumping RBC and many other celltypes, by virtue of interaction with polysaccharide residues of cellsurface glycoproteins, were found to be widely distributed in na­ture. They were named lectins. Many of them, such as the phyto­haemagglutinins (PHAs), are of plant origin. The PHAs are beingwidely employed for studying cell surface properties and cellulartransformations. Conconavalin A (Con A), the most familiar lectin,

is isolated from the jack bean, (anavalia ensiformis and is capable oj

47

HEAL WITH HERBS

agglutinating a variety of somatic and germ cell lines and restoringthe growth of virus transformed fibroblasts in tissue culture. Somelectins can agglutinate tumour cells from amongst normal cells. Forexample wheat germ agglutinin (WCA) clumps mouse carcinomacells readily. Soybean agglutinin (SBA)and ConA can agglutinate celllines transformed by viral or chemical carcinogens. Some are usedto induce mitosis in lymphocytes. Thus the lectins are proving to bevery useful tools in oncology and cell biology though their physi­ological role in nature is still a puzzle.

Naturally occuring antagonists of a phospholipid substance pro­duced by the human body, namely Platelet Activating Factor (PAF),have helped to identify it as one of the important chemical media­tors in septicaemic shock, bronchial asthma and anaphylaxis.

Cingkgolides A, B, C - bitter terpenoid principles extracted fromthe root bark of the ancient maiden hair tree, Ginkgo biloba, areamong the most potent PAFantagonists known. Nobody knows whyplants should produce molecules with PAF antagonistic activitywhen PAF itself does not occur in the plant world.

Many other examples can be cited. Reserpine is a valuable toolin exploring the autonomic nervous system; taxols are employed instudying microtubular structure and function; phorbol diesterswhich are potent co-carcinogens occuring in croton oil, help incancer research; phlorizin from the root bark of the apple tree isused to induce experimental diabetes in laboratory animals; mor­phine and its congeners help characterize the endogenous opioidreceptor system. It is important to realize that plant products, even

if not of direct clinical utility may command substantial researchpotential and medical research is ultimately conducted with clinicalgains in view. This is one more reason to take good care of our greenheritage. A case in point is the Ginkgo biloba, always prized for itsornamental value. On this very cc;unl it was exploited to nearextinction. But it survived, thanks to temple gardens of the Far East,and we have learnt a lesson.

48

Veratrum viritJe {Page 38}

Close up of leaves

49

Rauwolfia serpentina (page 37)

Azadirachta indicA {Pages 41',62}

,,'.-

Commiphora mukul (Page 42)50

Guggul gum

Atropa bel/adona (Page~44,59)

Datura stramoniumfPages 44,59)

51 Datura seed

Panax ginseng (Pages 53,60)

'?

; A~~.•~;.'

;lw_

Hyoscyamus niger (Pages 44,59)

Root of P. ginseng

52

I,I~I~PINC;S'I'111~SS1\,'1'

lIllY

The work of daily living is very hard. Modern man pi­

roeutte's about from morning to nighttrying to accomplishthe day's tasks. Oftentimes the nights are not exempt too.All this tends to wear the body. And when the bodily

systems break downthere are problems.Peptic ulceration, hy­pertension, nervousdiarrhoeas, spasticcolon, headaches,

anxiety neurosis,chronic fatigue areamong the many dis­orders putativelylinked to stress.Someofthem can be lethal,like myocardial infarction. Others do not kill but make life a misery,like insomnia.

Orthodox medicine offers no solution to stress.Several drugs areavailable to provide symptomatic relief when individual systemsbreak down and a smaller number to help them to recover. Butthere are none to prevent system breakdown in the first place.Traditional systems of medicine and folk remedies in various partsof the world, however, have been using various plants for theirreputed health promoting, rejuvenating effects. These agents pre­serve health rather than cure disease. Chinese herbal pharmaco­

poeias alone list several like Ginseng (Panax ginseng), Chineseliquorice or Gan cao (G/ycyrrhiza ura/ensis), Dang gui (Angelica sinen­

sis), H u mu (Aralia chinensis), Jejube or Da zao (Zizyphusjujuba), Yuanzhi (Polygala ten uifolia) , Wu wei zi ($chizandra chinensis), Siberian

ginseng (E/eutherococcus senticosus) among others. In India the Ayu r­vedic and Unani systems of medicine offer Guduchi (Tinospora

cordifolia), Shatavari (Asparagus racemosus), Ashwagandha (Withania

HEAL WITH HERBS

somnifera), Haritaki (Terminalia chebu/a), Amlaki (Emblica officina/is),

Punarnava (Borrhavia diffusa), Gurke (Diospyros peregrina) and others.Modern medicine has no name for these remedies but one has been

proposed - adaptogenic drugs. They are to be characterized bythe qualities of improvement of endurance against stress, generalresistance against infections and retardation of the aging process.

The first problem facing researchers is to substantiate or refutethe claims made on these plants. Since a precise definition of stressis lacking and standardized conditions and objective parameters tomeasure stressare difficultto formulate, an outright clinical trial withthese agents is often not feasible. A beginning has been made withanimal models - testing endurance, adrenocortical function, anti­ulcer activity etc. in forced swimming, restraint, cold, anoxia andother forms of stress. Immunomodulatory activity can be assessedmore objectively, at tissue and cellular levels, such as throughmacrophage function, lymphocyte a('tivity, cytokine secretion andso on. Rejuvenating properties may be studied as effects on in vitro

parameters of cellular aging such as cell migration, the length ofinterphase and cellular life span. However the entire field hasgenerated a lot of controversy. Some view the very idea of anadaptogenic drug with skepticism. But researchers are hopeful.They reason that, given the subtle control mechanisms existingwithin the living body, specially the neurohumoral and endocrinecoordination, it is not impossible to have remedies that act at keysites of integration to improve the overall adaptibility of the system.Since the complex homeostatic control mechanisms are themselves

not fully understood, a full explanation of the action of these plantscan only come slowly through painstaking research. But the chal­lenge must be accepted.

Another problem is to isolate the active constituents. Thoseadaptogenic plants which have been chemically analyzed havealready yielded numerous potentially active compounds. Ginsengfor example contains triterpenoid saponins (including ginsenosidesRb, Rcand RgJwhich have been linked with endurance promotingand hepatoprotective action; ginsenoside Rb specially increasesRNA, protein and cholesterol synthesis in the liver; panax acidwhich stimulates the heart and elevates basal metabolic rate; gly­cosides of which panaxin stimulates the heart and brain stem

54

KEEPING STRESS AT BAY

centres and ginsenin which is hypoglycaemic; various sterols; asesquiterpene (pancene); polyacetylenes like panaxynol;kaempferol; choline; an antioxidant and essential oils. Screening ofindividual constituents for pharmacological activity is a stupendoustask. And it rakes up the old conflict between traditional remediesand modern therapeutics. Herbalists argue that once a plant isbroken down into its constituents, the reinforcing and balancinginfluences in the whole are lost and we may not recognize theactivity or worse still, notice only the toxic effects of the part. Buthere again it is a question of challenge. Interactions may be complexbut an effort must be made to understand them. In this context, in

vitro testing has one major drawback - it does not reflect thebalance of the plant extract acting at its intended site in vivo.

Stress is distressing and the search for anti-stress remed ies toopromises to be a long and taxing venture. But so long as mankinddoes not lose curiosity, enthusiasts will venture forth. The prize islucrative. If plants can help our body to help itself, this is no reasonto scorn them. Is not prevention better than cure?

55

rl'III~C.I~'IJ(~(»)li'

I..INI{

The globular shape of the human eyeball is maintained to

a large extent by the pressure of the fluid, the aqueoushumor, that it contains in its anterior chamber. Aqueoushumor is being secreted and drained continuously, the

balance of the two

processes sustainingthe intraocular pres-sure within a narrow

range. Increase ofpressure has deleteri­ous effects on the

eye, affecting bothstructure and func­

tion and leading toeventual blind ness.

This is glaucoma. Itwas realized long agothat the glaucoma-tous deterioration invision can be arrested

by normalizing theeyeball tension.

Pilocarpine, an alkaloid extracted from the leaflets of the shrub,Pilocarpus microphyllus, which is native to Brazil, permits doctors todo just that. Drops of pilocarpine narrow down the pupils (miosis),

improving the patency of the draining tissue meshwork at the angleof the anterior chamber and allowing aqueous to flow out morefreely. At the same time the eye is fixed temporarily for near vision(spasm of accomodation). In acute glaucoma, frequent drops ofpilocarpine is invaluable in controlling the acute rise in pressurebefore definitive surgical intervention is possible. In chronic glau­coma, drugs are the mainstay of treatment and pilocarpine is oneof the oldest and most widely used miotic drugs.

THE GLAUCOMA LINK

Pilocarpine has other interesting properties. The Brazilian natives

knew that chewing Pilocarpus leaves would produce liberal saliva­

tion. Pilocarpine also increases the flow of tears, mucus, gastroin­

testinal and pancreatic secretions. And it is one of the most powerful

diaphoretics known - subcutaneous injection of as little as 5 mg

provokes almost immediate and copious sweating. Litres of water

may be lost from the body. Extracts or tinctures of jaborandi leaves

may stimulate hair growth and are therefore used in 'hair tonics'.

Physostigma venenosum grows on the West African plains. From

the dried ripe seeds of the plant comes a shiny white crystalline

powder that turns pink on exposure to air. This is the alkaloid

physostigmine - the African answer to pilocarpine. Like the latter,

physostigmine produces miosis and spasm of accomodation and

may be used in glaucoma or to restore pupil size after it has been

deliberately dilated for eye testing. But its mechanism o'f action isdifferent.

Physostigmine is a powerful stimulant of organs innervated by

cholinergic nerve fibres. It preserves the neurotransmitter acetyl­

choline at such nerve endings by inhibiting the enzyme acetylcholi­

nesterase. In toxic doses it produces marked central excitation,

gastrointestinal distress and muscular weakness. It was actually used

by native African medicine men in trials for witchcraft. The accused

was forced to take a paste of the ripe seeds. If vomiting occured,

he was spared much of the toxic effect and was declared innocent.

Otherwise the drug poisoned the individual who was then consid­

ered guilty and died anyway. Thus Physostigma venenosum came tobe known as the ordeal bean.

But this very effect of cholinergic stimulation can be put to good

use at reasonable doses. Physostigmine can reverse the paralyzing

action of curare-like drugs. A systematic study of the chemical basis

of the action of physostigmine led to the introduction of the

neostigmine group of anticholinesterase agents. They are employed

(n reversing the action of curariform drugs following surgery under

anaesthesia and in treating l11yasthenia gravis. As for physostigmine,

its principal use continues to be for the glaucomatous eye. It also

finds occasional use in the treatment of atropine or bel/adona

poisoning which blocks a particular fraction of the cholinergic

57

HEAL WITH HERBS

activity within the body but fortunately can be countered by theanticholi nesterase agents.

Two plants - two alkaloids - two drugs to preserve vision inglaucoma with other spinoffs. But do we have the vision to save ourplant wealth? This is the question vexing mankind today.

() 1..1) I) l..LlN'I'S ,NI~"T

Ill~)II~I)II~S

'Old is gold', said the sages of antiquity. When one

considers medicinal plants there is truth in this saying.

We are still using many plant derived drugs in much

the same way as our ancestors did. The autonomicnervous system alone

provides several ex-amples. Bel/adona

preparations havebeen described in

ancient India and

physicians have usedthem for centuries.

We are still using at­

ropine (from Atropabel/adona and Datura

stramonium) and sco-

polamine (from Hyoscyamus niger and Scopolia carni"olica) as antimus­

carinic agents. Pilocarpine, a natural cholinomimetic alkaloid fromthe leaves of Pilocarpus jaborandi and related species, remains one

of the most widely used miotics in glaucoma. Physostigmine fromthe West African Calabar bean, Physostigma venenosum is still being

used to treat atropine poisoning.

However man's ingenuity has not permitted him to get bogged

down in tradition and stick to the old uses. He is now using

scopolamine in transdermal patches as the most effective remedyfor motion sickness. While still using pilocarpine in glaucoma he hasnow incorporated the drug into polymer matrices that can be

inserted into the conjunctival sac (pilocarpine ocuserts) thereby

eliminating the need for frequent drops.

The poisonous effects of colchicine, an alkaloid from the Autumncrocus, Colchicum autumna/e, was known to the ancient Creeks and

preparations of the plant were recommended for articular pain inthe 6th century AD. Von Storck first used colchicine for acute gout

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in 1763 with remarkable results. Today colchicine is known to be amitotic inhibitor and is being tried for prophylaxis or treatment offamilial mediterranean fever, primary biliary cirrhosis, psoriasisand other rlisorders.

Ammi. visnaga was used in ancient Egypt for its spasmolyticproperties. Cromolyn sodium was synthesized in 1965 in an attemptto improve upon the bronchodilator activity of khellin, a benzopyr­one compound derived from this plant. Although devoid of thebronchodilator activity of the parent molecule, cromolyn turned outto be the first of an unique class of compounds, the mast cellstabilizers, and found clinical use as a prophylactic antiasthmaticand antiallergic dru'g.

Yohimbine is a selective, reversible, U2- antagonist compoundobtained from the bark of Pausinystalia yohimbe. It also occurs in thesarpagandha root. It is being investigated for the treatment of malesexual dysfunctions such as psychogenic impotence, postural hypo­tension and diabetic neuropathy.

The Far Eastern Ginseng (Panax ginseng and related species) andthe Chinese Ginkgo (Ginkgo biloba) are hugely popular as ancientrejuvenating drugs. While these claims are still unsubstantiated thepharmClcological investigations of these plants have yielded severalmolecules with interesting activities. Ginseng contai nsseveral activesaponins. Cinkgolides are platelet activating factor antagonists. Astandard ised extract of ginkgo leaves to alleviate cere bral ischaemiais currently one of the most prescribed drugs in Germany!

Therefore we see that the gold of olden days can sparkle anew.One only needs to be patient and care to polish them.

60

I)II~rl'ilNI)1)IIIJf;S

'0ietand drugs are two s.ides of the same coin', observed

Charaka the great Indian physIcian with charactenstlc

insight. Take vitamins for example. One may regard

them as nutrients or one may regard them as drugs butthe fact remains that

they Me essential fornormal metabolism

and most of them

come from plants(Cyanacobalamin orVitamin B12 is a nota­

ble exception). Ordietary fibres for tila~matter. An averagemixed diet providesenough to keep the

bowels moving regularly. And if you are asked to prescribe laxatives

for constipated elderly patients you would probably choose bulk

forming agents like wheat bran, PSliiju,,~ c:' ;:~:-,:"1husk. Theanthraquinone laxatives also come from plants, like senna from ll1e

leaves and pods of Cassia spp and cascara from the powdered bark

of Rhamnuspurshiana. Pectins are matrix polysaccharides from plant

cell walls present in a wide variety of fruits and vegetables. They

have been extensively used in comlti-nation with other agents as

non-specific antidiarrhoeals though their therape~tic uti:ity is con­

troversial. Starch blockers is the popular name for a group of

glucosidase inhibitors obtained from legumes such as the Red

kidney bean, Phaseolus vulgaris. By blocking starch hydrolysis and

hence intestinal absorption of carbohydrates, they may be of value

in weight reduction and in diabetic patients.

The Indian diet contains many plant products 01 rnedicinal value

which are being investigated for therapeutic uses both here and

abroad. Karela or the Bitter gourd (Momordica charantia), tradi-

HEAL WITH HERBS

tionally taken as a bitter at the beginning of a meal, has hypo­glycaemic activity confirmed in normal and alloxan-diabetic rabbitsas well as in diabetic patients. So too does the Neem (Azadirachta

indica). Neem oil has been a successful contraceptive in primateexperiments. Extracts of fresh neem leaves are reported to haveantiseptic and wound healing properties. Amla (Emblica officina/is)

has been shown to be protective in careulein induced pancreatitis.Garlic (Allium satiyum) is credited with a favourable anti-hyperlipi­daemic profile. Spices like turmeric, clove, cinnamon also holdtherapeutic potential. Ayurveda describes a group of plants calledrasayana which influence diverse bodily functions favourably. Someof them like Guduchi (Tinospora cordifo/ia), Shatavari (Asparagus

racemosus) and Ashwagandha (Withania somnifera) have been shownto induce sepsis in rats besides their immunostimulatory role in man.As deficient functioning or aberrations of the immune systemunderlie many diseases it is not surprising that rasayana plants maybenefit in diverse disorders and preserve health.

Given that dietary and non-dietary herbal products are often ofmedicinal value, a question that has plagued scientists is that whythis should be so. Why would plants evolve countless moleculesoften with complex chemical structures and with such a vast arrayof activity in diverse species?A common view isthat such moleculesconfer a survival advantage. This may have positive connotationssuch asthe attraction of pollinators or it may be in the negative senseof being toxic deterrants to predators or growth inhibitors to com­peting species in the local environment. Whatever the reason, manis in an unique position to benefit from plant resourcefulness. Socoupled with botanical pharmaceuticals it is important to take stockof the 'nutriceuticals' - plants that are used as food and are alsoof value as therapeutic or prophylactic medicines.

62

f;111~1~~l'II)~'I'f)

I~()Iltl'JI~"I'If)~

A medicine taken off the shelf is not just the active

drug. Theactivepri nci pleisgenerallyreq u ired inminutequantities thatare too small to handle in everyday life.Therefore, it must be dispensed in an inertvehicle that

adds bulk. Other in-

gred ients may benecessary to maskun p leasanttastesandsme Ils.Mostanti biot­

ics are intensely bit­ter, antihistamines

are salty - given assuch patients willsi mply refuse to takethem. Taste and

sme Ilareparticu larlyimportantwith ch ild ren. Some components are added to ensu rethatthe active ingred ientsare re leased atthe inte nded site, others

to prevent their release at unintended sites. Still others may benecessa rytosta b i Iizea ndma intai ntheu n ifo rm ityofthep repa ratio nitself. Thus, the finished product, the dosage form, entails muchmore than the actual drug. Consider the familiar rou nd or oblongentity - the tablet. Apart from the d rug, it incorporates a fi lie r toadd bulk, a binderto maintain the compactshape, ad isintegrantto ensure that it breaks up effectively in the gut and sometimes acoating to make it more pleasant or appealing or to preventpre matu red isintegrationi ntheacid icenvi ron me ntofthestomach.Besides ,so meothe rma te ria Ismaybe mixedwiththe initia Ipowd erto make surethatitflowsfreelyth rough thetabletmaki ngmach inewithout clogging orifices and does not stick to the dies as it iscompressed into tablets. And no prizes for guessing that plantssu pplythe lion'sshareofsuch indispensibleaidstoformulation ofmedicines.

· .- ...-. ~. - ... - - .-- .. - - . - - - - - - -_. -.-

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The polysaccharide starch is the end product of photosynthesisand occurs in all plant organs in greater or lesser quantity. It is thechief filler for the tablet. Wheat (Triticum vulgare), rice (Oryza sativa),

maize (Zea mays), potato (Solanum tuberosum) and arrowroot(Maranta arundinacea) are among the commercial sources of medici­nal starch. Microscopically, starch exists as grains, the nature ofwhich varies accordi ng to source. For instance; rice starch has muchsmaller grain size than potato starch. Drying causes starch grains toshrink and fissure. The dry grains when placed in water will imbibeit and rapidly expand to their original size. This causes tabletdisintegration.

On complete hydrolysis starch yields glucose but in its nativestate it has two polymeric components - amylose, a straight chainpolymer of glucose and amylopectin, its larger branched counter­part. The proportion of the two varies depending upon source.Starch with high amylose content gives the flexible film for tabletcoatings. Starch may be chemically modified to alter its physicalprop2rties. Dextrins or starch gums are produced by acid hydrolysisof native starch. They are water soluble and used as mucilage.Further modifications can alter solubility characteristics. Sterilizablemaize starch is completely insoluble, even on autoclaving, and isused as a lubricant for surgical gloves and asa vehicle for medicateddusting powders.

Cellulose, the other major plant polysaccharide, is the principalstructural componentof plantcell walls. It isa straight chain polymerof glucose highly resistant to degradation. Partial depolymerizationof cellulose, brought about by acid hydrolysis of purified woodcellulose, gives microcrystalline cellulose. This is available as acolloidal water dispersible material which forms thixotropic gels athigh concentrations and is used as suspending agent or as a tabletfiller, binder, disintegrant or lubricant. Methylcellulose, car­boxymethylcellulose, hydroxy- methylcellulose are alkylated cellu­lose derivative~ differing in solubility and viscosity. They find use as~;,-,uisltying or suspending agents. Cellulose acetate phthalate orc:e!laphate is a mixed acetate and phthalate ester of cellulose. Thisacid resistanl material often forms the enteric coating of tablets andcapsules.

64

GREEN AIDS TO FORMULATION

In contrast to starch and cellulose, gums and mucilages areheterogenous polysaccharides of hexose, pentose and uronic acid

residues. Gums form sticky colloidal solutions or gels with waterwhile mucilages give colloidal, viscous but less sticky solutions.Gums are obtainable as exudates from plants, mainly tropical ones,

and their production may be increased by wounding thp plant

tissues. They are believed to be pathological products j"esulting frombacterial transformation of starch and cellulose. Mucilages, on the

other hand, occur as normal water absorbing constituents in manyplants. Gums and mucilages are employed as suspending, emulsi­

fying and thickening agents. Mucilages are also utilized as the base

for enemas and to mask the taste of bitter preparations.

Gu m acacia from Acacia senegal and some other Acacia species is

one of the most widely used pharmaceutical hydrocolloids as it iscompatible with many drugs. It is also called gum arabic as it occurs

in the plant as potassium, calcium and magnesium salts of a complexbranched chain polysaccharide, arabic acid. Gum tragacanth from

Astragalus gummifer also finds wide use, particularly in skin prepara­tions containing materials required to dry out on the skin. It is also

an effective denture fixative. Red gum or eucalyptus gum from

Eucalyptus rostrata and related trees is an astringent in lozenges and

gurgles. Karaya gum (from Sterculia urens) and ghatti gum (Anogeissus

latifo/ia) are obtained from native Indian plants - the former has

laxative and adhesive properties, the latter is used as acacia substi­

tute. The guar gum plant, Cyanopsis tetragonolobus also grows in

India. The hydrocolloid guaran extracted from its seeds can form asticky and highly viscous dispersion. It differs from other gums inthat it is a natural constituent of the endosperm and is probably not

a pathological plant product.

The fixed oils from plants are essentially mixture of long chain

fatty acids of glycerol. They occur in all tissues but are commerciallyextracted from sites where they serve dS food reserves. Some ofthem have nutrient and medicinal properties of their own. Wheat

germ oil from the endosperm of wheat, Triticum aestivum is rich in

Vitamin E. Olive oil expressed from the ripe fruits of Olea europaea

has mild laxative effect. But they are more frequently employed,

after purification, as soothing emollients in skin preparations likecreams, ointments and liniments or as vehicle for injection of lipid

65

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soluble drugs. Included in this category are Arachis oil (groundnut

or peanut oil- from the seeds of Arachis hypogaea), Maize or Corn

oil (expressed from Zea mays germs after the starch has been

separated), Cottonseed oil (from seeds of Gossypium herbaceum),

Sesame or Til oil (from Sesamum indicum seeds) and several others.

Soyabean oil (from the seeds of Glycine soja) is somewhat different

in its properties because of its rich content of polyunsaturated fatty

acids and its chief pharmaceutical use is as a source of stigmasterol

for steroid production. Theobroma oil expressed from crushed and

roasted Theobroma cacao seeds is a byprod uct in the production of

cocoa. It is solid at room temperature but is melted by body heat.

Thus it is a popular base for rectal suppositories and vaginal pessaries

which have to melt to release the active drug. Fractionated Palm

kernel oil (oil from Elaeis guinensis kernels subjected to selective

solvent fractionation and hydrogenation) and Coconut oil (from the

dried endosperm of Cocos nucifera) are used as ointment bases.

When fractionated, coconut oil will not solidify and may be used

. as base for oral liquids.

Unlike the fixed oils, the essential oils are volatile and aromatic

plant oils. They are obtainable by mechanical pressue, steam

distillation or solvent extraction and generally owe their fragrance

to oxygenated derivatives of terpene and sesquiterpene residues.

They are indispensible in many medicaments to mask the unpleas­

ant smells or tastes of the active ingredients and are added to many

more to make them more pleasant or appealing. Examples includeoils obtained from Cardamom (Elettaria caradamomum), Cinnamon

(Cinnamomum zeylanicum), Fennel (Foeniculum vulgare), Lemon (Citrus

limon), Peppermint (Mentha piperita) and various other spices. Ba­

nana, blackcurrant, cherry, lemon, lime, mint, orange, pineapple,

strawberry and vanilla are among the soft fruit flavours used in

medicaments. The pharmaceutical industry attaches great impor­

tance to the selection of suitable odour and flavour imparting

materials. Natural volatile oils may be fractionated to improve their

suitability for formulation requirements. It is very difficult to repro­

duce the flavour of volatile oils through synthetic chemicals because

of the complexityofthe natural mixtures but efforts have been made

to isolate and use principal odour imparting constituents like gera­niol.

66

GREEN AIDS TO FORMULATION

Thus, from binder to dispersant, from base to coating, from filler

to flavou r, plant materials are necessary at every ste p - prod uctionto consumption - of medicines, even if they do not provide the

active drug itself. This again is food for thought.

67

'J'III~III~lllll'l..)II~I..'J'INC. PC)'J'

Look around you and you will find plants unoostrusively

helping you in almost every sphere of your daily lives. Thevery air you breathe contains oxygen, which is given offby the photosynthetic activity of green plants. The food

you eat is largelyplant; the dress youwear may be cottonor linen; the houseyou live in may bewhole or part wood;the electricity youuse may be corningfrom coal fired

plants; the vehiclesyou ride have rubbertyres and the materialI am writing all this on - is paper! So also it has been in medicine.Plants have helped us in all ways - therapeutic, analytic, diagnostic,prophylactic - all through recorded history.

Syrup ipecac may be found in the emergency ward of manyhospitals as an emetic to expell orally ingested poisons. It acts bothlocally and centrally. The syrup is prepared from the roots ofipecacuanha (Cephaelis ipecacunha), long used by the natives ofBrazil and sold as secret remedy for loose stools to the FrenchGovernment in 1658. It was employed empirically in dysenteriestill Vedder in 1912 identified that the emetine which it contains is

active against pathogenic amoebae. Emetine is an intestinal andsystemic amoebicide, in which respect it has now been replaced byless toxic drugs.

Chymopapain is a proteolytic enzyme obtained from the latexof the papaya plant, Carica papaya. It is injected intervertrebally inthe treatment of sciatic pain due to herniation of intervertebral disksof the lumbar spine. Chemonucleolysis occurs leaving the fibrous

Asparagl.lS-racemosus (Pages 53, 62)

Emblica officinalis (Pages 54, 62)

Close-up of leaves (Inset)69

Root of A. racemosus

Withania somnifera (Pages 53,62)

Colchicum autumnale (Page 59)

Seeds of A. hypogaea70

Triticum vulgare (Page 64)

Carica papaya (Page 68)

71

Mentha spp (Pages 36,66,73)

Berberis arista (Page 74)

Nicotiana tobacco (Page 77)

Close-up of flowers

; \

Thymw~spp (Page73)

72Senecio sp[1. (pa!=Je 70)

THE HERBAL MELTING POT

ring of the disk intact. Utmost care is taken to avoid inadvertent

injection into the lumabar subarachnoid space rather than theherniated disk, as this can lead to paraplegia and subarachnoid

haemorrhage.

Inulin is a starch (plant polysaccharide) obtained from the tubers

of Dahlia variabilis and other members of the Compositae family. It

is metabolically inert, non-toxic, not distributed to the tissues and

rapidly cleared from the circulation by glomerular filtration alone.These qualities that make it ideal for measurement of glomerularfiltration rate after intravenous administration.

The fruit of Synsepalum dulcificium (miracle fruit) yields a glyco­

protein appropriately named 'miraculin'. It i~ tasteless on its ownbut when applied to the tongue makes sour substances taste sweet.Thus acids will taste sweet after miraculin! Italso improves the flavorof foods.

The dried stalks of the seaweeds, Laminaria digitata and Laminaria

c/oustoni can imbibe water and swell up to several times their originalvolume. Sterilized hollow or solid tubes of laminaria (laminaria tents)

have been used to dilate the uterine cervix for procuring abortion.

Plantago ovata (isapgul) husk has similar properties and can also bemade into tents to dilate cavities. It is better known as a bulk formi nglaxative.

Menthol comes from the volatile oils of various species of Mentha

and can also be synthesized. It forms a soft or liquid mass whentriturated with camphor, phenol and many other substances. Men­thol inhalation (usually with benzoin and various essential oils) or

ointments (with camphor and essential oils) are used for the symp­tomatic relief of upper respiratory tract congestion. When appliedto the skin it dilates blood vessels evoking a sensation of cooling

followed by mild analgesia. It also relieves itching and is used increams, ointments, pastes and lotions forthis purpose. The essentialoils of numerous plants, including such well known ones as Gera­nium (Pelargonium spp), Juniper Vuniperus communis), Lavender

(Lavandula spp), Lemon (Citrus limon), Lemon grass (Cymbopogon spp),

Orange (Citrus sinensis), Peppermint (Mentha spp), Pine (Pinus spp

- turpentine oil), Rose (Rosa spp), and Thyme (Thymus spp) areused as rubefacients, counter irritants, carminatives, flavouring

agents, other food additives and in pf'rfumery.

73

HEAL WITH HERBS

Gums, particularly gum aca.cia and tragacanth, find wide usageas demulcent bases for cutaneous medication, emulsifying agentsfor oils administered orally and suspending agents for insolublepowders. Agar-agar and algin are seaweed gums used commercially.Agar can form an effective gel with water in concentrations as lowas 1 in 2000. It is widely used as a base for microbiological culturemedia. Sodium alginate is often used in propietofY antacid formu­lations. Algin has the unusual property of binding the heavy metalstrontium and can prevent its absorption into the body. Semisyn­thetic cellulose derivatives like carboxymethyl- cellulose and hy­droxypropylmethylcellulose, are widely used in artificial tears,contact lens solutions, other ophthalmic preparations, as suspend­ing agents for nasal drops and in toothpastes. They also find use ashydrophilic colloid laxatives.

The cowhage plant, Mucuna pruriens, is indiacted in Ayurveda formale sexual disorders like psychogenic impotence and unexplainedinfertility. Recent studies reveal that this plant can reduce serumprolactin levels and benefit animal models of extrapyramidal syn­drome. Clinical studies have been started to see if formulations of

this plant can have a therapeutic role in Parkinson's disease.

Berberine is a quaternary alkaloid occuring in Indian barberry(Berberis arista), Golden seal (Hydrastis canadensis) and several otherrelated plants. It kindled interest because of its antimicrobial prop­erties. Subsequent studies showed it to have good antisecretoryactivity in vitro and in vivo, and capable of interfering with choleratoxin induced secretion at a step beyound adenylyl cyclase stimu­lation. The drug is moderately active in human cholera. The antise­cretory activity if explored further could lead to a novel and potentantisecretory agent.

Two ofthe most widely used plasma expanders are derived fromplant prod ucts. Hetastarch or hyd roxyethyl starch is starch rich inamylopectin and esterified on the hydroxyethyl groups of sugar unitsin the starch polymer. With an average molecular weight of450,000, a 6% solution of hetastarch has nearly the same colloidalosmotic pressure as human plasma. Therefore, it is frequently usedin the short term expansion of plasma volume in hypovolaemia andimpending shock due to trauma, burns or surgery. Hetastarch is alsoused during leucopheresis procedures to improve yield of granu-

74

THE HERBAL MEL TINe POT

locytes and may be incorporated in extracorporeal perfusion fluids.

Fermentation of cane sugar by a certai n strai n of LeuconostoC mesen­

teroides gives dextrans, which are glucose polymers of varyingmolecular weights. Low molecular weight dextrans like Dextran 40

(average molecularweight40,000l improve the microcirculation byplasma volume expansion as well as by their favourable effects onerythrocyte flow characteristics. Dextran 70 and Dextran 110 solu­

tions have oncotic tension eq ual to plasma at 6% concentration and

are employed for volume expansion and prevention of post-opera­tive thromboembolic disorders.

These interesting titbits give a glimpse of the treasures in the

herbal melting pot. All through history man has added gems andtrinklets to it. Modern day researchers continue the tradition. All are

not put to use. But the melting pot remains. If some researcher ata future date salvages a gem from the past and employs it to

advantage, kudos to him. We, as ancestors, cannot but be proud ofthe achievements of our posterity.

75

111~"Tl'111~f)l~1)I.JlN'I'S !

Our green neighbours help us in countless ways and what

concerns pharmacologists the most are the therapeuticdrugs they supply. After the initial euphoria with purelysynthetic compounds, orthodox medicine is taking a

fresh look at natural

products and this isreflected in the

changing attitude ofthe pharmaceuticalindustry. The Lancet

reports that 15 yearsago none of the top250 drug firms had aresearch program in-volving higher plantsbut now over half of

them do so. The World Health Organisation is trying to coordinateefforts.

But there are other very pertinent reasons why herbal productsmerit a close look. Consider the dangers of adverse drug reactionsand drug interactions. One reason for the lay popularity of plantmedicines is their reputed safety and freedom from side effects.While this may be true of some preparations it is certainly not trueof all. And there will always be unscrupulous suppliers who mixherbal ingredients with undeclared potent non-herbal drugs likeaminopyrine, phenylbutazone, dexamethasone and others.

Poisonous plants abound worldwide. Many are known to be soand therefore shun. Others are consumed in the beliefthatthey areinnocuous like senecio (Senecio sppl, an active herb in bush trees,which can cause hepatic necrosis and fibrosis; sassafras root bark(Sassafras albiduml, also used in herbal teas, contains safrole whichis hepatotoxic and carcinogenic; liquorice (Glycyrrhiza glabral whichon being taken internally can cause oedema and hypertension by

BEWARE OF PLANTS!

yielding glycyrrhetinic acid which has mineralocorticoid activity.Several plants have known antihelmi nthic activity but many of themare so toxic that they have fallen into disrepute. Not long ago manypharmacopoeias listed chenopodium oil (from Chenopodium am­

brosioides) which is capable of expelling roundworms and hook­worms and male fern extracts (from Dryopteris filixmas) as a

tapeworm vermifuge. Both have caused fatalities by their drastic

purging action. Some plant based antihelminthics are still used inveterinary medicine.

Ayurvedic preparations often contain a multitude of plant ingre­d ients and it has been emphasized that all steps of preparation must

be meticulously followed to neutralize harmful activity. Some con­traindications to usage have been mentioned in the ancient textsthemselves. Experience is showing that there is a flip side to

Ayurveda too. Ignorance of the correct methodology of preparation,lack of standardization, availability without prescriptions, concomi­

tant use of Ayurvedic and non-Ayurvedic formulations, inappropri­

ate dosing and arbitary usage have been identified as the chiefreasons behind adverse reactions to Ayurvedic drugs.

Finally, there is the problem of abuse of natural products like

opium, cannabis, cocaine and others. Intensive efforts are being putin by physiologists, pharmacologists, toxicologists and other re­

searchers to understand the pharmacology of these substances andtheir cellular and molecular basis of action. Tobacco smoking too

represents a powerful addiction, which is to the alkaloid nicotine.Nicotine chewing gum and nicotine transdermal patches are tworecent innovations that are being employed to wean away smokersfrom the fatal tobacco fumes.

77

rl'III~1~(Jrl'(JI11~()I~

I)II1'll)ll'(~()(;­N()SY

No one doubts that plants can be invaluable and yet it

remains a grim fact that the past several years has seen

very few natural compounds enter the pharmacopoieaof conventional medicine for good. One major problem

is the specificity of

natural compounds

which is often verydifficult to deter­

mine, thereby mak­

ing them liable to be

frowned upon by cli­nicians. Forskolin

from the Indian

plant, Coleus forskohli

is one of the few spe­

cific exogenousstimulators of cyclic-

adenosine monophosphate synthesis discovered. It has been re­ported to have a positive inotropic effect independent of G-adren­

ergic receptors and also inhibit platelet aggregation in vitro. Butexamples like C. forskolin are rare.

Typical are the flavonoids. They are a group of more than 700different chemical compou nds widely distri buted in terrestrial flora.

They are being intensively investigated and seem to inhibit variousenzyme systems and possess correspondingly diverse pharma­cologic actions. It is this very lack of specificity which is troubling.

How does one go about identifying medicinal plants in the first

place? The blessings of serendipity are always welcome and haveled to great discoveries in the past but they are hard to come by.One starting point could be to turn to folk remedies and traditional

systems of medicine used by various ethnic groups. There are

encouraging convergences in the emperical use of medicinal plants

in various parts of the world and there are uniquely different

THE FUTURE OF PHARMACOGNOSY

remedies too. But it must be borne in mind that specific diagnosesare often lacking in folklore medicine and remedies are prescribedon the basis of symptoms the cause of which are unknown. Appro­

priate care must be exercised in identifying the traditional remedies

for such diffuse ailments as 'indigestiion' or 'impurities in the blood'.

This is just the beginning of the problem. Once an useful plant

has been identified the next step would be to identify the active

component for that particular therapeutic application. Given thefact that a plant may have hundreds of components, many of themactive, some of them interacting and a substantial number of themhitherto unknown, this is a herculean task.

Nevertheless, scientists have taken up the challenge. Ethnophar­macological research programs in India, China, Russia and else­where are on. India is fortunate in that it has one of the world's

richest flora with about 120 families of plants comprising 130,000species. The use of about 2,400 of these have been mentioned in

Ayurvedic texts and many others are used by tribal groups to thisday. Ancient Indian scholars like Charak, Sushruta, Vagbhatta have

given detailed descriptions of medicinal plants and their uses in their

classical works which suggests that efforts to trace drugs from thissource would not be in vain.

The other, more capital intensive approach, would be to screen

families of plants systematically for therapeutically active principles.By means of multidisciplinary efforts and tests carefully chosen toreflect future clinical applications, agencies like the National CancerInstitute in USA are doing so with some success. But the path from

a crude extract to a marketable drug is a long and tedious one and

laden with pitfalls. A lotof effort must necessarily go into convincingadministrators and financiers of the feasability of such programs.

Despite that fact that most pharmacological research is con­

ducted with modest resources, the literature is teeming with inter­

esti ng resu Its. It wou Id be a shame to let these go waste by notfollowing them up, particularly because with the advancement ofmolecular sciences, the refinement of isolation and structure

elucidation techniques and the current spate of optimism amongreasearchers, we are now in a much better position to identify new

drugs.

79

HEAL WITH HERBS

Let us keep up hope and continue the glorious tradition that

began when our earliest ancestor plucked the leaves from the plantsthat grew outside his cave and applied them to his wound. And who

knows there might be another morphine, digoxin or reserpinelurking just round the corner!

80