STUDIES ON SOME ORGANIC COMPOUNDS ISOLATED FROM LAURACEAE, SOLANACEAE & EUPHORBIACEAE FAMILIES

Abstract

The Indian system of medicine is considered to be the oldest system which is being fruitfully practised even to this day. To alleviate human suffering from diseases, peoples of all ages and countries have been using various drugs obtained both from plants and animals. The origin of materia medica of India dates back to the period of Rigveda. In this book, there are several hymns in the praise of "Soma" which has now been characterized as Ephedra pachyelade. Ayurveda, the materia medica of the Hindus, was greatly enriched during the first few centuries of the christian era (200 A.D. to 600 A.D.). A number of famous "Acharyas1* such as Charak, Sussuta, Narhari, Madanpal, Bagbhatta and Bhav Misra devoted most of their valuable time in evolving a system of curative medicines obtained from Indian medicinal plants. It was during this period that a number of standard books on medicine such as Nighantu and Bhav Prakash etc. (based on careful observations) were written. A substance known as *Sanmohinirt is also said to have been used as a general anaesthetic in the time of Budha, and a mention of some kind of surgical instruments had also been made. Before the British rule, Ayurvedic system, supplemented to some extent by Unani system was the only system of medicine practised in India. The Britishers 2 brought with them a relatively more scientific system based on empirical knowledge of chemistry, known as allopathy. The indigenous system, although denounced as unscientific had its own metaphysical basis of diagnosis e.g. the acceptance of three vikras, Vata, Pitta and Kapha in diagnosing various diseases. However, in absence of much patronage, the indigenous system survived and even today it caters to the need of majority of the Indian population, particularly in rural areas through Ayurvedic dispensaries run by District Boards. Ayurvedic medicines have been found to be very specific for certain diseases such as Holorrhena antidysentrica for dysentery, gauwolfia serpentina for insanity, ftdhatoda vessica for respiratory diseases, Boerhavea diffusa for dropsy and ga,ssl& sLlata for ringworm etc. Such information has undoubted ly been extremely useful in guiding plant chemists to examine different plants of proved medicinal value. In most of the cases, it has been found that the allopathic system uses only the active principle, while the Ayurvedic system uses the whole plant. It will not be out of place to mention that in some cases the whole plant is found to be more effective than its active principle. As such, there is no question of any sort of rivalry between the two systems. Rather, it is worthwhile to examine the vast available literature on Ayurveda compiled by Votaries of the system and see if it can be of some service to the people. In fact, the potentialities and possibilities of medicinal plants and vegetable drugs have not yet been properly and fully developed, but due to awakened interest in plants, some work has, however, been carried out in India and abroad. Americans are developing herbotherctpy at a rapid pace. As a result of this, a large amount of knowledge has accumulated for the benefit and guidance of the indigenous practitioner. However, due to lack of coordination between the chemist, physiologist and practitioner, the investigations of the chemists do not always serve a useful purpose. The establishment of a number of drug research institutes and regional research laboratories ( mainly C.S.I.R. sponsored) in the country augurs well for the future, and it is hoped that useful investigations carried out at these institutes shall go a long way in making the lives of suffering millions worthliving. This will be possible only when plants of proved efficacy are grown in gardens maintained by Governments to avoid adultera tion. A number of empuria may also be opened at suitable places so that drugs and plants may be collected at a proper season and distributed to various research institutes for systematic investigations. 4 Historical development of plant chemistry: The plant chemistry dates back to the middle of the seventeenth century A.D. If plant chemistry is regarded as the art of resolving plants into their chemical constituents, or at least as that of isolating the most important components in the form of pure chemical compounds, then C.W. Scheele may be regarded as the founder of the modern plant chemistry. The number of plant products known before his time was very small and perhaps not a single compound had been prepared in a perfectly chemically pure state. The two processes of isolation viz. dry distillation and steam distillation of plant products were frequently employed in his time. Extraction with solvents was not at all popular at that time. It was through dry distillation that George Agricola (1546) and Alexander Pedemontanus had obtained succinic and benzoic acids from amber and benzoin respectively. Essential oils were obtained by steam distillation of Valerius cordis and gave interesting results. In the seventeenth century, the solvent extraction method was also successfully employed by Angel us Sala who obtained sugar and salt of sorrel from plant extracts. The idea of acquiring the fundamental knowledge of plants by using force and decomposing them completely by fire, advanced by theoritical chemists, Duclos and Dudart of Academiedes 5 sciences (1666) proved useless after some time. Some fourteen hundered plants were dry distilled at this institute with the result that all the products obtained were more or less similar. In the eighteenth century, the extraction methods again came to the fore front when Boulduc, Boerhaave and Newmann employed them though without any noteworthy results. The best contribution during this period was that of Marggraf who demonstrated the preparation of cane sugar from indigenous plants in 1747. It was Scheele who first raised phyto-chemistry out of this stagnation. He obtained tartaric, citric, malic, oxalic and benzoic acids in the pure form as a result of well planned and carefully conducted experimental investigations. In the last years of his life (1786), he discovered a new vegetable acid, gallic acid which was obtained by the spontaneous decomposition of gall nuts. These investigations of Scheele though not very significant greatly exceeded in value all the work carried out before his time in the field of plant chemistry. The early years of nineteenth century are very important so far as the discovery of a number of important alkaloids is concerned. In 1804, Derosne and in 1806, Serturner discovered morphine though narcotine had been obtained by the former a year ago. 6 Many alkaloids were discovered during 1803-1837. The enormous progress of phyto-chemistry which resulted from the discovery of Serturner, led also to the discovery of many non-alkaloidal vegetable principles during this period. The important investigations of Leibig and Wohler published in 1837 became the starting point for the discovery of a group of glucosides. They had established the fact that hydrolysis of glucosides gave glucose as one of the products. This work is also significant in the history of the vegetable enzymes. The scent and essential oil industry of India dates back to the reign of Jehangir and his queen, Noori- Jehan who discovered the scent of rose. But the systematic investigations on essential oils and the separation of their individual constituents in a chemically pure state began first in the nineteenth century. This was made possible by the preparation and separation of derivatives of compounds by reacting them with different reagents. The first pure compounds prepared from this group were menthol, thymol and eugenol. The occurrence of many active principles in minute quantities in plants posed a problem for the plant chemists. But now micro-analytical methods, tracer techniques, chromatography and a number of other methods 7 employed in the separation, purification and identifica tion, have solved the problem to a great extent. A number of physical methods such as absorption spectra, X-fay crystallography, infra red, ultra violet, mass spectrography and N.M.R. have proved of immense help in elucidating the basic structures of complex organic molecules. Thus the hithertojbedious investigations are becoming relatively simpler and phyto-chemical investigations are receiving a fresh impetus. Development of plant chemistry in India. In the foregoing pages, it was mentioned that much useful information was collected by ancient Hindus about plants and drugs. There had been further useful additions to this branch upto the end of the Gupta dynasty. But for about a thousand years, before the establishment of British supremacy in India, no significant work had been carried out on plant chemistry. The Britishers brought with them the useful knowledge of modern Chemistry and Botany. The abundance of medicinal plants in the country awakened their interest in Indian indigenous drugs. Many informative books were written on these plants with their botanical names so that these plants could be properly classified according to their genera and families. Some of them also carried out preliminary investigations on the plants they came across. Ainslie was the first man who published his 8 book • materia medica of Hindustan* in 1828} Shangnessy produced * The Bengal Pharmacopla" in 1844 and Waring wrote " Indian Pharmacopla" in 1868. Besides these, William Jones (His botanical observations on select Indian plants), Roxburg (Flora indica), Wallach, Buchanan, Hamilton, Griffths Graham, John Fleming (catalogues of medicinal plants), Royle and Wright are some of the outstanding early personalities in the field of plant chemistry. F.J. Monat and F.N. Machamarla and other botanists did very useful work in classifying a large number of Indian medicinal plants. Asides these foreign workers, Indian scientists also carried out some good work. K.L. Dey wrote • The indigenous drugs of India" and while U.C. Dutta wrote the "materia medica of Hindus" in 1877. A gradual progress in the field was noticed with the development of commerce, medicine and science. Dymock's first book "materia medica of western India" in 1883 was a valuable contribution. The publication of "Pharmacographlca India", embodying important researches of Dymock, Warden and Hooper, was a great event in the growth of plant chemistry in India, and the fact that it remains an indispensable book of reference even today adds to the credit of its authors. For a long time Dymock*s "Pharmacographlca India" remained the main book of reference till 1924, the subject 9 — received the attention of Col. R.N. Chopra who emphasised s the importance of assespient of all the indigenous drugs from modern chemical and pharmacological stand point and a definite scheme of work was chalked out at the Indian School of Tropical Medicine, Calcutta. Since then, a lot of work in this direction has been done at various institutes in India, chiefly at Delhi, Calcutta, Allahabad, Agra and Andhra Universities} Bose institute, Calcutta; Unani and Tibbiya College, Delhi} Ou Indian Institute of Science, Banglore} Forest Research Institute, Dehra Dun, Central Drug Research Institute, Lucknowj National Chemical Laboratory, Poonaj Regional Research Laboratory, Jammu} Presidency College, Madras and a number of other places. The opening of a separate centre for advanced studies in plant chemistry at the University of Delhi, Delhi under the able guidance of Prof. T.R. Seshadri, augurs well for the future of plant chemistry in India. The natural orders of plants in which active principles have been found to occur are comparatively few in number. Out of more than two hundered families, only the following are quite important from medicinal point of view: Acanthaceae, Apocyanaceao, Anacardiaceae, Compositeae, Cucurbitaceae, Euphorbiaceae, Labiatae, Lauraceae, Leguminaceae, Oleaceae, Papaveraceae, Ranunculaceae, Solanaceae, Umbliferae, Convulvolaceae and Rubiaceae. 19 Phyto-chemical investigations carried out by the author: The author has investigated four new Indian medicinal plants, viz., Litsea consimilis (Familyi Lauraceae), So^anum f erox Linn. (Family: Solanaceae), Euphorbia hirta Linn, and Euphorbia thymifolia Linn. (Family: Euphorbiaceae), which have not been worked up so far for their active principles. A number of lauraceae plants specially belonging to Litsea species, are a source of fatty oils, alkaloids, essential oils and triterpenoids. The barks, leaves and seeds of some Litsea species have found wide applications in medicine (1) . The bark of Litsea chinensis which is demulcent, astringent and aphrodisiac, is used in diarrohea, dysentery and also as an antidote to bites of venomous animals. The seeds are aphrodisiac and the oil from its berries is used in rheumatism. The bark of Litsea polvantha is astringent and used in diarrohea, dysentery and as a stomach stimulant. The leaves of Litsea stocksi i have been used for the irritation of bladder and urethra. The seed oil is used in the treatment of sprains, bruises and itch. The seed fats of Litsea plants, besides being medicinally important are of commercial Interest as a source of excellent detergent, satisfactory lubricating agent for watches and other delicate machines and a wetting agent for insecticidal preparations (2-3). 11 Litsea conslmllls, grows plentifully on the hilly tracks of Naini Tal. The oil from its berries is used by the local people in the treatment of rheumatism, various skin diseases and for healing wounds. This plant has hot been investigated so far. The seeds, fruit coat and bark of this plant have been chemically analysed. Narang and Puntambekar} Miyamictu and Nomura} Child and Nathanael} and Hata have chemically examined the seed fat of a number of Litsea species, i.e. frH?gea chinensis, LJAssa CUraU, Litsea lanuglnosaT U-fr39a a^yXanica,, LJ,*?S5a, .1aPQi4ca» Lltsea longlfolia and Litsea cubeba (4-7). The seed fat of Litsea eonaimllis was chemically examined by the author and was found to be slightly different from those investigated by earlier workers. The essential oil constituents of the seeds were found to be different from those of the essential oils of the seeds of other Litsea species (7). It was, however, interesting to observe that some of the essential oil constituents of the seeds of Litsea consimilis were identical to those found In the leaves of Lltsea zeylanica and Wum CHbqtm (8-10). Fruit coat and bark fats of Lltsea consimilis were also analysed. The major saturated acid component in the fruit coat fat was found to be lauric acid. Moreover, the glyceride of capric acid, which does not occur in any fruit coat fat of lauraceae plants so far investigated (11-13), was found to be present in the fruit coat fat of this plant. The amino acid make-up of the fruit coat was determined and found to be similar to that of the seeds (14) except that the fruit coat did not indicate the presence of proline and cystine. The bark oils generally consist of oleic and palmitic acids as the major components along with minor amounts of stearic acid (15). The results of the author, show that the bark oil of Litsea conslmiUa contains lauric acid as the major component with a little capric acid instead of stearic acid, p - amyrin was obtained from the petroleum ether extract of the bark on chromatographing It over Brockmann alumina. The alkaloids of the bark and seeds were isolated and examined. The alkaloid isolated from the seeds appears to be quite different from alkaloids already reported in other Litsea species (16-20). The seed fat of Lltsea consimllls has also been examined for its possible use as a lubricant and in the preparation of alkyd resins and varnishes. The results were found to be quite encouraging. A large number of plants belonging to solanaceae family have been used medicinally in various diseases (21) i.e., cough, asthma, diarrohea, dysentery, dropsy, chest pains, rheumatism, ulcers, fevers etc. Fats, 13 alkaloids and saponins have been isolated from a number of Solanum species and examined by earlier workers (22-46). Solanum ferox Linn., grows wildly in Garhwal (U.P.), Madras, Assam, Bihar, Orissa, Ceylon and China. Various Parts of this plant JUe. roots, leaves, stems, flowers, seeds and fruits have been used medicinally in sore throat, cough, asthma, chest pains, dropsy and rheumatism. This plant has not been worked up so far for its active principles. The seed fat and the alkaloidal content of the fruits of golanum, ferox Linn, have been examined. Some plants belonging to Euphorbiaceae family grow wildly throughout India and have found wide applica tions in medicine (47). Different Euphorbia species have been found to contain terpenoids, steroids, higher hydrocarbons, higher aliphatic alcohols, lactones and alkaloids which have been examined by various workers (48-78) . Euphorbia,, hj,,rta hXW» arld Euphorbia thymifolia Linn., grow wildly throughout India in plains and lower hills. These plants have been medicinally used in various diseases i.e. bowel complaints, cough, dysentery, colic pains, bronchial affections, asthma, ringworm, snakebite and skin diseases. Although some varieties of Euphorbia hirta viz. procumbens, pedilantus calcaratus and pedilantus tehuacanus have been chemically examined 14 by earlier workers (79), no work seems to have been done on the active principles of Euphorbia hirta Linn. The petroleum ether and ethancl extracts of the stems and the ethanol extract of the flowers of this plant were chemically examined. It is interesting to observe that Euphorbia hirta Linn, contains myricyl alcohol, taraxerol and ellagic acid, besides the presence of friedelin,p - amyrin, hentriacontane and } -sitosterol already reported (79) in some varieties of Euphorbia hirta. A very little work seems to have been done on Euphorbia thymifolia Linn. The isolation of 5, 7-4- trihydroxy flavone-7-glucoside from the stems and leaves and the chemical examination of the essential oil constituents have been reported (8O-81). On examining the petroleum ether and ethanol extracts of the whole plant, myricyl alcohol, taraxerol, tirucallol and hentriacontane were isolated and characterized. The free organic acid pattern of the stems and the leaves of both these plants was also determined. The investigations carried out on the above four Indian medicinal plants form the subject matter of the subsequent chapters.