[PUBLIC] Some Observations on Hypoglycemic Activity of Momordica charantia

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Some Observations on Hypoglycemic Activity of Momordica charantia

Author: V. N. Sharma, R. K. Sogani, R. B. Arora

Type of Publication: Pre-clinical

Date of Publication: July 1960

Publication: Ind. Jour. Med. Res. Vol.48, No.4, pp.471-477, July 1960

Organization: Department of Pharmacology and Experimental Therapeutics, S. M. S. Medical College, Jaipur

MOMORDICA CHARANTIA is a plant cultivated throughout India. It is commonly known as Karela (Hindi), Sushavi (Sanskrit), Pavakkachedi (Tamil), Kakara (Telgu) and bitter gourd (English). Fruits, leaves and roots of this plant are used in Ayurveda for a number of disease, including Diabetes mellitus. Hypoglycemic effect of Momordica charantia from Puerto Rico has been reported by Rivera (1942). Chopra et al. (1956) have suggested that it should be investigated for hypoglycaemic activity and possible clinical usefulness. The present report is the work done in this Laboratory on the fruit of this plant as hypoglycaemic agent.

MATERIAL AND METHODS

The juice of Karela fruit was obtained by crushing it in a mortar and straining through a muslin cloth. The juice was stored in refrigerator and used within 48 hours. Juice samples older than this were discarded. In the present paper this juice has been referred as Karela juice.

Healthy adult rabbits (1.2 kg to 1.5 kg) and rats (150 g. to 200 g.) were used for the present work. Blood sugar estimations were done by the method of Asatoor and King (1954). Diabetes was produced in rabbits by the injection of alloxan 150 to 175 mg/kg. Intravenously as 2 per cent aqueous solution. Rats were given alloxan in dose of 175 mg./kg. subcutaneously. The studies were carried out in normal and diabetic animals.

Twenty-eight normal rabbits were taken. They were divided in 5 groups. In three groups of 6 each and one of 4 animals, ascending doses of Karela juice (2 c.c./ kg., 4 c.c./kg., 6 c.c./kg and 12 c.c./kg.) were given orally after a period of 12 hours of fasting. The blood sugar was estimated at the time of giving the drug and at intervals of one hour for a period of 5 hours. The rest of the 6 animals were kept as controls. Six diabetic animals were also similarly observed after a dose of 6 c.c./ kg. of juice orally, while 4 diabetic animals were kept as controls.

Glucose tolerance test was also done. Twelve normal and 12 diabetic rabbits were used, out of which 6 normal and 6 diabetics were kept as controls. All the animals were kept without food overnight, although water allowed. In the morning, fasting blood sugar was estimated. In the test animals, 6 c.c./kg. of Karela juice was given orally, while in controls nothing was given. After 11/2 hours all the animals , test and controls, were given glucose 3.2 g. /kg. orally. The time interval of 11/4 hours was given so that peak activity of Karela juice may coincide with the maximum glucose absorption time. Blood samples for sugar estimation were subsequently collected at half-hourly intervals for a period of 21/2 hours.

Two ests, one of 10 normal and other of 10 diabetic rabbits, were taken. Each of these were divided into two groups of each. Five normal and 5 diabetic rabbits were given 6.c.c./kg. of juice once daily. The other 5 normal and 5 diabetic were given 6 c.c./kg. of Karela juice twice a day. Blood sugar estimation were done on alternately days after overnight fasting.

For finding out preventive action of Karela juice on alloxan-induced diabetes, the method described by Mukheriee et al. (1958) was used. Forty rats were used and their fasting blood sugar was found before starting the experiment. They were divided into 4 groups of 10 each. One group was kept as control, while the three groups (I,II,III) were test groups. Groups I, II and III were fasted overnight. Single dose of Karela juice was given orally in increasing order so that each animal of group I received 2 c.c./kg.; each of group II, 6 c.c./kg.; while each of group III received 8 c.c./kg. Two hours after Karela juice feeding, each animal was given alloxan 175 mg./kg. in 2 per cent solution subcutaneously. No food was given during this period. Control group was similarly given alloxan after fasting period but no Karela juice was given. Blood sugar of all the animals of the four groups was estimated 48 hours after alloxan administration.

RESULTS

The effect of karela juice on the blood sugar levels of normal and diabetic rabbits is summarized in Table I. Two c.c./kg. and 4 c.c./kg. dose of Karela juice does not have any significant action on blood sugar level. Twelve c.c./kg. dose shows almost similar action as seen in 6 c.c./kg. appeared to be the optimal dose for the Karela juice. The maximal fall in blood sugar level is seen after 2 hours in normal rabbits, and it starts rising from 3 hours onwards. In diabetic rabbits, however, the blood sugar continues to fall up to 4 hours and then starts rising. The fall is more marked in normal than in diabetic animals. Some of the typical responses are given in Graph 1.

Glucose-tolerance test in normal control group showed a peak rise (never more than 180 mg. per cent) at the end half an hour which returned to a level slightly above at the end of 1 hour then gradually went on falling during the rest of the test reaching quite near fasting level at 21/2 hours. In test group, where Karela juice was given there was a fall of blood sugar level during initial 11/4 hour period. However, once glucose was given blood level shot up reaching peak level after one hour and returning almost to fasting level in 21/2 hours. During this there was a period when blood sugar level exceeded 180 mg. per cent. In a few cases blood sugar level went on slowly rising to a peak level at 2 hours and here it did not return to normal at 21/2 hours and blood sugar level was more than 180 mg. per cent for ashort time. In diabetic control rabbits, on administration of glucose, blood sugar level immediately rose to very high levels (600 mg. to 650 mg. per cent) and then gradually started falling though at 21/2 hours it was still uch higher than fasting level. After Karela juice fasting blood sugar level falls during initial 11/2 hours waiting, but on giving glucose it starts rising. The rise is gradual, continue for 21/2 hours but is not so marked as in control group. The finding are summarized in Table II and some of the typical curves are given in Graph 2.

In the series of once daily and twice daily feeding of 6 c.c./kg. of Karela juice, there was a slow and steady fall of blood sugar level in normal and diabetic groups. The fall was more marked in the groups receiving Karela juice twice daily. However, with both dosage schedule 80 per cent of normal and 90 per cent of diabetic animals died at varying intervals of 5 to 23 days. Some of the typical observations are given in Graph 3.

No preventive action of Karela juice on the diabetogenic action of alloxan was found in rats as is clear from Table III.

Toxicity and slide reactions. In this connection three observations need special mention. Firstly, that in two female pregnant rabbits when Karela juice 6 c.c./kg. was administered as a single dose it produced uterine haemorrhage and death within few hours. No such action was seen in non-pregnant rabbits. The drug appears to be an abortifacient. Secondly, in animals in whom continous daily administration of Karela juice was done. Majority died within 23 days. Thirdly, all the 10 rats which received Karela juice intraperitoneally in doses of 15 to 40 c.c./kg/ became sluggish within one hour and died in 6 to 18 hours.

Although side reactions and toxicity of the juice are marked, but the preparation of Karela used is a crude one and the possibility of separating out pure non-toxic hypoglycaemic factor from this crude preparation cannot be ruled out. Chemical separation of active principles and further experimental study alone will throw more light whether this drug can be of value therapeutics or not.

SUMMARY

   1. Hypoglycaemic activity of orally administered Karela juice is reported in normal and diabetic rabbits.
   2. Side reactions and toxicity observed have been reported.
   3. If chemical separation of non-toxic hypoglycaemic active principle is possible it may prove a useful oral antidiabetic agent.

V. N. Sharma, R. K. Sogani, and R. B. Arora

This wprk was supported partly by grant-in-aid from Unichem Laboratories, Bombay, for which the authors express their gratefulness to the Director, Shri A. V. M. Sc. (London).

REFERENCES

Asatoor, A., King E. J. (1954). Simple colorimetric blood sugar method. Biochem. Jour., 56, xIiv.

Chopra, R. N., and Chopra, I. C. (1955). A review of work on Indian medical plants, 75. ICMR Special Report Series No. 30, New Delhi.

Chopra, R. N., Nayara, S. L., and Chopra, I. C. (1956). ‘Glossary of Indian Medicinal Plants’, 168-169. Council of Scientific & Industrial Research, New Delhi.

King, E. J., and Wooton, I. D. P. (1956). ‘Micro-analyss in Medical Biochemistry’, 25-27. J. & A. Churchill, London.

Mukherjee, S. K., and De, U. N. (1958). Studies on D 860- Another new oral hypoglycaemic sulfonamide. Ind. Jour. Med. Res. 46, 223-233.

Mukherjee, S. K., De U. N., and Mukerji, B. (1958). Effect of ‘Nadlisan’ of course of alloxan diabetes in rats and rabbits. Ibid., 46, 57-62.

Rivera, G. (1942). Amer. Jour. Phar., 113, 281.

Sepha, G. C., and Bose, S. W. (1956). Clinical observations on the antiduabetic properties of Pterocarpus marsupium and Eugenia jambolana. Jour. Ind. Med. Assoc., 27, 388-391.