Some CNS effects of Datura stramonium L (Solanaceae) in mice

Z.H. MBWAMBO,* R.L.A. MAHUNNAH,* M. RUNYORO*
J. FULGENCE,** J.G. SAYI,** and G.M.P. MWALUKO**

*Traditional Medicine Research Unit
**Department of Clinical Pharmacology
Faculty of Medicine, Muhimbili Medical Centre
P.O. Box 65001, Dar es Salaam, Tanzania

ABSTRACT

The leaves of Datura stramonium L. (Solanaceae), or mnanaa in Swahili, are used us an additive in local brews to increase the intoxicating effect of the beer. In Tanzania, there are three Datura species which are used medicinally. One of these is D. stramonium. Because of its extensive use by the traditional beer producers, the plant attracted attention for studies on the active ingredients in its leaves. The plant was found to contain a mixture of the alkaloids hyoscyamine, and hyoscine,. Of more interest, was the finding that with the recemization of hyoscyamine, some atropine is formed. When an extract from the leaves was tested in laboratory mice versus phenobarbitone (a known depressant) its effect was found to be closer to that of amphetamine, i.e. behaving as a (CNS) stimulant. The interpretation of this result must be carefully done. However, since the dosage of the leaves put in local brew is unknown, and no one has studied it, there is a strong need for this work to be done. It is tempting to denounce the practice off-hand, yet the potential it possess must be critically and scientifically examined. Is it possible, perhaps, to counteract the CNS alcohol mediated (particularly respiratory centre) depression, with the extract in correct formulations? There are more questions remaining than answers. However this does not remove the potential application of the observed results.

Central nervous system

Introduction

The genus Datura (Solanaceae) comprises of ten species which are globally distributed in the tropics and the warm temperature regions. In Tanzania three species are found, namely, D. stramonium L., D. metal L., and D. innoxia L., which is least represented. All the three species have medicinal properties, and are employed in both traditional and modern medicinal applications. D. stramonium L. is the most widely used species. In Tanzanian traditional medicine, D. stramonium L. is used to alleviate or cure a number of diseases and conditions.

Leaves of the plant are used as an additive in local brews, where they are claimed to increase the intoxicating effect. The flowers are smoked as an asthma remedy. A combination of leaves and roots is used for the treatment of coughs, and snake bites (Chhabra et al., 1989).

D. stramonium L. contains from 0.2 to 0.45% alkaloids, the chief of which are hyoscyamine and hyoscine. But some atropine is also formed from the hyoscyamine by racemization. D. stramonium seeds contain about 0.2% of mydriatic alkaloids and about 15-30% of fixed oils. The roots contain, in addition to hyoscine and hyoscyamine, digitoyl esters of 3, 6 - dihydroxyatropane and 3, 6, 7 - trihydroxytropane, respectively and alkylamines (Trease and Evans, 1978).

Atropine has a stimulant action on the central nervous system, and depresses the nerve endings to the secretory glands and plain muscles. Hyoscine lacks the central stimulant action of atropine, but its sedative properties enable it to be used in the control of motion sickness. Atropine and hyoscine are used, to a large extent, in ophthalmic practice, to dilate the pupil of the eye (Trease and Evans, 1978).

Materials and methods

Powdered leaves of Datura stramonium were soaked in diethyl ether. After 5 min. a 10% ammonia solution was added to make a basic solution (pH 8), which was left to stand for one hour at room temperature. The diethyl ether extract was filtered through cotton wool. To the filtrate, some water was added, and left to stand until a clear separation of the two phases was observed. To the dimethyl ether extract, 1% hydrochloric acid was added followed by gently shaking and subsequent filtration through cotton wool. The filtrate was again treated with 10% ammonia solution, to make a basic medium, and then the alkaloids were extracted with chloroform. The solvent was evaporated at reduced pressure to give viscous liquid extract, which was soluble. This was used in the subsequent experiments.

The following study was, therefore, undertaken with a view to establish the activity of D. stramonium on the Central Nervous System due to its extensive use by traditional beer producers, and as a therapeutic agent in both traditional and modern medicine.

In the subsequent experiments, the drugs used consisted of the following:

(a) amphetamine (dextro): 2.5 mg/kg body weight, dissolved in double distilled water, and injected intraperitoneally;

(b) phenobarbitone: 5 mg/kg body weight, dissolved in double distilled water, injected intraperitoneally; and

(c) an extract of D. stramonium: 5 mg/kg body weight, injected intraperitoneally.

The animals used were white albino mice which weighed 25-30 grams (reared in the laboratory, and housed at a concentration of 10 per cage, and with free access to water and food).

The mouse open field consisted of a 46 cm diameter white base, which was divided into 6.5 cm squares by pale blue lines. The wall (30 cm high) which surrounded the base, was made of aluminum sheeting. The apparatus was illuminated by a 60 watt white bulb, positioned 60 cm above the floor of the apparatus. All observations were carried out between 0900 and 1200 hours.

The parameters measured were: (a) ambulation: the number of squares crossed; (b) rearing: the number of times the animal lifted its forepaws and raised itself from the floor (standing on its hind legs); (c) grooming: the number of times the animal stopped and cleaned or preened itself and (d) defaecation: the number of faecal boli deposited during the 3 min observation period.

The data that were obtained were tabulated and analysed statistically and the results that were obtained are summarized in Table 1.

Results

Table 1. Effects of D. stramonium extract on white albino mice as compared to d-amphetamine and phenobarbitone

* P = 0.003 Extract compared to phenobarbitone
** P = 0.002 Extract compared to phenobarbitone.

It was observed that mice treated with the extract of D. stramonium had an ambulation that was almost similar to that of amphetamine. The extract also significantly increased the rearing activities. The mice given phenobarbitone had decreased ambulation scores.

Discussion

The open field test is a method whereby the emotionality of a rodent is assessed (Candland and Nagy, 1965; Tachibana, 1982 and Halliday, 1966). This test has been widely used to assess the emotional state of animals for the following reasons:

(a) the ease with which animals may be placed into a novel, stressful environment
(b) the ease with which its basic behaviour can be observed and measured
(c) the simplicity of the technique

Some investigators suggest that animals explore or are active because they are fearful. This implies that with continuous exploration, the fear decreases (i.e. familiarization occurs). The opposing viewpoint is that fearful animals explore little until fear decreases. Less fearful animals explore more than animals that are more fearful (Candland and Nagy, 1968). In this case, the central nervous system stimulant amphetamine, was used as a basis for assessing the effects of the extracts of Datura stramonium on the open field behaviour of the white albino.

Since the main alkaloids of the extract are hyoscyamine and hyoscine, the expected results were that, the ambulation would have been decreased significantly, compared to that of amphetamine or similar to that of phenobarbitone, due to their sedative properties. Instead, the extract acted like a stimulant, the open field ambulatory behaviour being similar to that of d-amphetamine. More central nervous system effect tests of the Datura stramonium extracts are being done.

References

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