Journal of Ethnopharmacology, 8 (1983) 313-320 Elsevier Scientific Publishers Ireland Ltd.

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Short Communication

EVALUATION OF ASOKA ARISTHA, AN INDIGENOUS MEDICINE IN SRI LANKA

TEUNIS B. MIDDELKOOP and RUDI P. LABADIE

Farmaceutisch Laboratorium, Department Farmacognosie, Rijksuniversiteit Utrecht, Catharijnesingel 60, 3511 GH Utrecht (The Netherlands)

(Accepted February 12, 1983)

Introduction

In our laboratory, research is being done to support a cooperative project between Sri Lanka and the Netherlands. The aim of the project is expressed in its title: “Production Development and Optimization of the Quality and Preparation procedures of Ayur Veda Drugs in Sri Lanka”. The Ayur Veda (AV) system of medicine is still widely practised in Sri Lanka, especially by people living in the rural areas (Simeonov, 1975). The government of Sri Lanka endorses the AV system and its use, e.g. a ministry for indigenous medicine was established in 1980.

The Ayur Veda originated about 4000 years ago in India and is based on a collection of concepts quite different from those used in modern scientific medicine (Thakhur Chandrasekhar, 1974). The assessment of the efficacy and quality of an AV drug is therefore a research matter to be treated carefully when current scientific concepts in pathology and methods for assessment of drug action are applied. Our research on AV drugs has so far included: (1) establishment of the botanical identity of ingredients used to prepare the drug; (2) selection of an appropriate biological test to es- tablish a possible mode of action of the drug; (3) identification of the chemical constituents responsible for the effect of the drug. The result of this research can be used to standardize the drug and to optimize the quality and production procedures of the preparation. The first drug chosen for investigation is Asoka Aristha and our findings so far are reported here. The

Asoka Aristha was chosen because of its popularity in Sri Lanka and the lack of scientific data concerning it.

In the following sections the results of a literature study and field work in Sri Lanka are described: $2 deals with the drug Asoka Aristha and 5 3 with the main ingredient, Asoka bark. In § 4 and 5 5 the therapeutic claims of Asoka Aristha are compared with current scientific concepts of the pathology

0378-8741/83/$02.70 0 1983 Elsevier Scientific Publishers Ireland Ltd. Published and Printed in Ireland

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of menstruation and possible modes of action of the Asoka Aristha are discussed. In 8 6 conclusions are drawn from the results obtained so far and an outline for further research is presented.

2. Asoka aristha

The recipe used for preparation which is mostly accepted by AV physicians

TABLE 1

RECIPE FOR ASOKA ARISTHA

Procedure: (1) Prepare primary mixture (2) Add ingredients (3) Keep in a sealed vessel as stated in Process No. 2.

Primary mixture: Bark of Asoka tree 6000 g Pure water 614.4 e Kitul/Cane jaggery 1200 g

Ingredients:

Sinhala name Botanical name

Dhathaki Woodfordia fruticosa L. Kaladuru Cyperus rotundus L. Ginger Zingiber officinale Roscoe Dharuharidra Berberis aristata DC. Mane1 Nymphaea stellata Willd. Aralu Terminalia chebula Retz. Bulu Terminalia belerica Roxb. Nelli Phyllanthus emblica L. Mango Mangifera indica L. Sudu duru Cuminum cyminum L. Adhatoda Adhatoda vasica Nees. Sudu handun Santalum album L. Kaluduroo Nigella sa tiva L.

Part of plant

Flowers Yam Root

Yam

Seed kernel Seed Bark

Seeds

Quantity(g)

960 60 60 60 60 60 60 60 60 60 60 60 60

Preparation

Process No. 1: (1) Purify the Asoka bark in clean water (2) Crush the Asoka bark (3) Add the required quantity of water (4) Boil (5) Increase the concentration by reducing the quantity to l/8 (6) Strain to remove solids and cool the mixture (7) Add the jaggery and strain again

Process No. 2: (1) After crushing the ingredients add them to the above mixture (2) Cover the vessel and invert another vessel over it (3) Seal both vessels with clay (air-tight) (4) Keep in that position for 1 month and strain again

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can be found in the sinhalese Pharmacopoeia (Ayur Veda Pharmacopoeia, 1976). A translation of the recipe is shown in Table 1. The Asoka bark constitutes the main ingredient of the preparation (78% of the plant material to be extracted), followed by Woodfordia fruticosa flowers (12%) and 13 minor ingredients (10%). The result of the process is a fermented potion. Asoka Aristha is produced on a large scale in Sri Lanka by the state-owned Ayurvedic Drugs Corporation (manufacturer of 60% of the ayurvedic drugs commercially available in the country) (Arumainayagam Associates, 1980), and by some private commercial m~ufa~turers. On a smaller scale, it is prepared in AV hospit~s, AV clinics and by AV practitioners. The demand for Asoka Aristha is quite large. An estimation based on figures, provided by the large scale producers, shows that Asoka Aristha together with four other aristha’s comprises 82% of the total sales of aristha medicine (Aruma- inayagam Associates, 1981).

Information about the use of Asoka Aristha was obtained from four AV physicians, Their description of the medical indications were quite uniform. Further inquiry however indicated that the reported diagnostic criteria which are being used are not unanimous. Asoka Aristha has been indicated for women in cases of: (1) menorrhagia; (2) metrorrhagia; (3) leucorrhoea; (4) primary amenorrhoea, subfertility; (5) menstrual disorders in general; (6) for healthy complexion. Indications 1, 2 and 3 are related to the AV concept that Asoka Aristha has an “astringent and constipative action”. Indications 4, 5 and 6 show that Asoka Aristha is not only used as a drug for a specific ailment, but also as a tonic for women. The labels of Asoka Aristha preparations from three different manufacturers show some of these indications and always at least indications 1 and 2. The dose of the drug given in indications 1 and 2 is 15 ml of the potion twice or three times a day from the onset of the bleeding until it stops.

3. The Asoka bark

The recipe of Asoka Aristha shows that Asoka bark is the main in~edient of the preparation and in many AV textbooks the therapeutic properties of Asoka Aristha are attributed to the Asoka bark. In India, investigators of the classic Sanskrit texts on Ayur Veda identify the Asoka tree as Saraca indict L. (Narayana iyer and Kolammal, 1960). This identification is widely accepted in India and appears in many textbooks on Ayur Veda. In Sri Lanka, Asoka has also been identified as Saraca indica L. (De Fonseka and Vinasithamby, 1971). However, a botanical study done in 1968 revealed that Saruca indica L. is closely related to Suruca usoca Roxb. de Wilde, the latter being indi- genous to India and Sri Lanka. Saraca indica L. is indigenous in the Malaysian archipelago ~Zuyderhoudt, 1969). A field study performed in the Colombo and Kandy regions in Sri Lanka in 1981 showed that the two species could both be found there. S. ~~d~cu was mostly cultivated and could be found as

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an ornamental tree in gardens and near temples. The S. asoca tree was also found as cultivated specimen but also in habitats where a wild origin could be suspected. These observations lead to the conclusion that the Asoka tree in India and Sri Lanka is often erroneously identified as S. in&a, while the true botanical identity is S. asoca. Trimen (1893) noted in “A handbook to the flora of Ceylon” that the Saruca indica L. (S. asoca) is rather common in the lower regions of the country. Balasubramaniam (1982) however, noted that nowadays Saraca usoca is a rare occurrence in the lower regions of Sri Lanka.

In four Ayurvedic raw material shops (2 in Colombo, 1 in Kandy and 1 in Matara) Asoka barks were purchased and it was confirmed that this com- mercial bark is used in Sri Lanka for the preparation of Asoka Aristha. All four samples looked alike but were different from the authentic bark of S. usoca or S. indica. Deeper inquiry revealed that the bark for sale was taken from the tree Rhododendron arboreum Sm. a tree abundantly growing in the hill country above 1100 m. An authentic sample of the bark of Rhodo- dendron urboreum Sm. was supplied by the Divisional Forest Office at Nuwera Eliya, Sri Lanka. The commercial samples collected in Sri Lanka were identical (macro- and microscopic) with the authentic sample. A herbarium specimen has been examined in the Herbarium of the Botanical Garden of Peradeniya, Sri Lanka. Its local name is Asoka-mal. An inquiry among AV physicians showed that some were not aware of the fact that R. arboreum bark was used as an adulterant. One physician noted that the S. usoca bark was more effective than R. arboreum bark. The question remains as to when people started to use R. urboreum bark as a substitute.

From these facts about the botanical identity of the Asoka bark, it is concluded that in former days the bark of S. asoca was used in the pre- paration of Asoka Aristha and that nowadays mainly the bark of R. arboreum is used. Samples were taken in Sri Lanka from all three barks mentioned to use for research at our laboratory. We tested water and methanol extracts of the barks of R. arboreum, S. asocu and S. indica for direct stimulating activity on the uterus of the rat in vitro (Middelkoop, et al., unpublished). The uterus preparations were very sensitive for oxytocine and carbachol. Neither the Suraca nor the Rhododendron extracts gave reproducible con- tractions. Conclusively an oxytocic effect could not be demonstrated un- ambiguously. Considering the Saraca asoca (S. indica) these findings are in accordance with the results of two Indian research groups (Dhawan and Saxena, 1958; Bhatnagar et al., 1961). Satyavati et al. (1970), however, reported marked uterine stimulating activity in vitro.

Some articles have been published on the chemical constituents of S. indicu (usoca) bark. Sen (1963) mentions the occurrence of tannins, phenolic glycosides, saponins, a ketosterol, organic calcium salt and haematoxylin. Behari et al. (1977) reported the isolation of the phytosterols, campesterol, stigmasterol and p-sitosterol from the bark. In preliminary analysis of the barks of S, asoca and S. indicu no difference could be noted between the two barks using TLC and various eluents.

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A sample of S. asoca bark from Sri Lanka was used for the isolation of catechins and polymeric tannins. The presence of haemotoxylin and a ketosterol could not be demonstrated in the sample. From a sample of Asoka bark from India (bought in 1979 via Celo, Germany) we isolated bergenin. This sample was shown to be identical in a macroscopic and microscopic study with an authentic sample of S. asoca from Sri Lanka. However, the occurrence of bergenin could not be demonstrated in the sample of S. asoca bark from Sri Lanka.

One article has been published about the chemical constituents of the bark of Rhododendron arboreum (Hariharan and Rangaswami, 1966). The constituents described are taraxerol, ursolic acid acetate, betulinic acid and leucopelargonidin. The high yield of betulinic acid in the bark has been confirmed in our laboratory. The chemical analysis of the S. asocu bark from Sri Lanka is continued in relation to further experimental research on biological activity; the results will be published in separate papers.

4. The indication field of Asoka Aristha and the scientific knowledge of pathology of menstruation

First of all, it should be noted, that menstruation is not a purely physical phenomenon (Kerr and Parboosingh, 1974). The awareness of onset, re- gularity, bleeding and associated discomfort of menstruation are strongly influenced by psychological and cultural factors (Delaney et al., 1976). The tonic action of Asoka Aristha mentioned under indications 5 and 6, is dif- ficult to assess because of the general terms in which it is stated. It may be an indication of a weak oestrogenic action of the drug. The indication under 4, primary amenomhoea, is a typical example of cultural determination. In a society where the position of the women rests largely on her reproductive ability, the complaint of failing to menstruate will come at a younger age. Amenorrhoea after the age of X3-20 is usually a congenital polycausal symptom. Subfertility, like amenorrhoea, can have many causes, anatomical, e.g. congenital aplasia of vagina or uterus or ovaria, or a dysfunctioning of any part of the endocrine reproductive system. The third indication, leucor- rhoea, is caused by bacterial or fungal infections in the mucous membranes of the vagina. An effective medicine against it should have bactericide and fungicide activity or should be able, especially in the case of a fungal in- fection, to lower the pH of the mucuous membranes. The current opinion about the therapy of leucorrhoea is that, depending on the cause, local or systemic attack on the causal infection should be undertaken. The more specified indication for the use of Asoka Aristha are menorrhagia and metrorraghia. These conditions can be symptoms of an organic disease like adenomyosis, thrombocytopenia, cancer etc. When an organic cause is found, it is dealt with appropriately, but in many cases an organic disease is absent and the dysfunctional bleeding is of unknown origin. Until now the factors involved in menstrual bleeding and the roles they play are not all well understood. Recently the progress in our knowledge about hemostasis

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in menstrual endometrium has been reviewed (Christiaens ei al., 1982). No doubt the onset of menstruation is determined by the decline of the sex hormone production of the corpus luteum. The endometrium in the secretory phase desquamates because of the lack of the stimulating hormones and the curled arterioles in the endometrium are “pinched in” causing haemostasis and further disintegration of the endometrium tissue.

The decidual endometrium cells produce prostaglandins PGE, and PGF, as well as anticoagulating agents (Lindner et al., 1980). These prostaglandins have vasodilating and constricting properties and a stimulating action on the motility of the uterus. In women with dysfunctional bleeding it has been demonstrated that the concentration of prostaglandins in the uterus was much higher than in a control group of normal women (Willman et al., 1976). The neurotransmitters of the autonomic system also play a role in the contraction of the uterus during menstruation and an imbalance of the autonomic nerve system can be a causative factor in menorrhagia and other menstrual disorders (Shabanah et al., 1964). During menstruation the repair of the endometrium slowly starts by patch-wise proliferation of the basal endometrium cells, stimulated by the oestrogenic hormones secreted by the ovaries. On the fourth day of the menstruation the repair is com- pleted and the cycle starts again. In cases of menorrhagia bleeding may continue up to 7-10 days. The factors controlling the duration, apart for the increase of oestrogenic hormones, are still unknown.

The treatment of menorrhagia and metrorrhagia, following a thorough histological and endocrinological diagnosis to exclude organic causes, is many-sided: diagnostical curetage usually stops bleeding and in many cases prevents the recurrence of the condition. Oestrogens or progestagens in high dosage will stop the bleeding and administration of the “combination pill” can control the menstruation for a long time, Recently, a new treatment has been proved effective in menorrhagia. In a double blind trial,non steroidal anti-inflammatory drugs were shown to decrease the menstrual blood loss in women with dysfunctional bleeding. However, the drugs did not decrease the abnormally long duration of the menstruation (Toppozada et al., 1980).

5. Possible mode of action of Asoka Aristha and biological assay to test the effect

(A) Oestrogenic mode of action: administration of oestrogenic agents enhances the repair of the endometrium and stops the bleeding. An oestro- genie effect can be assayed by measuring the occurrence of cornification of the uterus epithelium in hypophysectomized rats after administration of sLl e drug.

(B) Oxytocic mode of action: although it has no equivalent in current _;cientific treatment, we can imagine that a mild oxytocic effect of a drug ::ould stop the bleeding by constriction of the blood-vessels in the myo- metrium. The effect can be assayed by measuring in vitro the direct uterine activity of the drug.

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(C) Prostaglandins synthetase inhibition: although no analgesic or anti- pyretic activity is ascribed to Asoka Aristha in the Ayur Veda, it may be a possible mode of action. This can be determined by testing the inhibiting properties of the drug in prostaglandin synthetase enzyme reactions in vitro.

6. Conclusions

At this stage of our investigation the following conclusive remarks can be made.

The botanical identity of the main ingredient of Asoka Aristha produced on a commercial scale in Sri Lanka has been established as the bark of Rhododendron arboreum Sm. (Ericaceae). The bark of Saraca indica L. or S. asoca (Leguminosae) mentioned in official preparation recipes is of no commercial significance as far as large scale production of Asoka Aristha is concerned.

Concerning the biological activity of Asoka Aristha, there types of experi- ments have been projected: an oxytocic, an oestrogenic and a prostaglandin- synthetase inhibiting mode of action. Results of experiments carried out on rat uteri so far seem to rule out the mechanism based on oxytocic action. These experimental results obtained with fractions from commercial Asoka Aristha and extracts of the barks of R. arboreum and S. asoca will be pub- lished in a separate paper. Further work on the other possible modes of action mentioned is continued.

With the restrictive value of positive or negative results of in vitro animal or biochemical tests for clinical efficacy in mind it appears that scientifically guided clinical trials on the therapeutic effect of Asoka Aristha are needed, besides our experimental efforts to clarify the therapeutic use of Asoka Aristha. Since the drug is in common use in Sri Lanka that country seems to provide an appropriate setting for such clinical trials.

Acknowledgement

We thank Prof. Dr. A.A Haspels for reading the manuscript.

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