Vol. 22 No. 4 September 2002

Two scientists at the Homœopathic Drug Research Institute, Lucknow, India, gave the chemical alloxan to rabbits to make them diabetic, then treated them with mother tincture of bitter melon, known to Hindi-speakers as karela and to botanists as Momordica charantia, and 45 % alcohol and saline solution to act as controls.

The experimenters, E. N. Sundaram and Sunil Kumar, chose this plant because of its traditional use throughout Asia as a remedy for diabetes, stomach pain, colic and fever.1

As well as measuring changes in the rabbits’ blood glucose levels their levels of growth hormone and prolactin were checked, too.

[Momordica charantia is not the same as the Momordica with a history of use in homœopathy for gut pain and diarrhœa, that is Momordica balsamica. As I have related (Homœopathica, February 2002) I have known M. balsamica 30c to improve cholesterol levels in my patients. M. charantia has been demonstrated to do this also. I have used M. charantia tincture made from the whole fruit with success in treating diabetes, and supplied Selene Homœopathics, Tauranga, with the fresh seeds of M. charantia to use to make medicine for my use and for sale. – Bruce Barwell ]

Fruit of M. charantia has been found to display anti-tumour activity.11 The acid acetone powder of seeds and acetone powder of seeds and of fruit of M. charantia have been reported to exhibit antillipolytic activity.26 Abortifacient activity has been detected in the fruit17 and in the seeds28 of M. charantia.

M. charantia is considered an effective hypoglycaemic agent in the management of diabetes mellitus. The fruit of this plant has been used as an anti-diabetic in India.19 The oral hypoglycaemic activity of the fruit juice of M. charantia has been investigated in normal and diabetic laboratory animals. 2, 5, 8, 12, 20, 23, 24

An insulin-like protein called “plant insulin”14 isolated from M. charantia has been shown to possess hypoglycaemic properties when injected subcutaneously in humans.3 The seeds of this plant have been reported to induce hypoglycaemia in diabetic rabbits.13

Although substantial work has been done on the hypoglycaemic activity of M. charantia on laboratory animals and in humans, the hypoglycaemic activity of M. charantia (homœopathic preparation) has not been properly investigated, which is the main objective of the Lucknow study. The work was undertaken to investigate the effects of M. charantia on blood glucose and serum growth hormone (GH) and serum prolactin (PRL) in alloxan induced diabetic rabbits.

Materials and methods
M. charantia was prepared in 45 % alcohol on the basis of maximum extractive value on air dried samples of fruit, as it does not find mention in Homœopathic Pharmacopoeia of India. Percolation method has been used in the preparation of the mother tincture.

Healthy adult rabbits (1000-1200gm) of New Zealand White were used. The experimental animals were grouped into three of 10 each. Each animal was weighed, and blood was collected from the marginal vein of ear lobes for blood sugar, serum GH and PRL estimations before commencement of the experiments. All the animals were intravenously injected with 150mg/kg of body weight of alloxan monohydrate in a citrate buffer of pH 4.5. Eight days after the alloxan injection, blood from each one of them was again tested and when hypoglycaemia (blood glucose of more than 250mg/dl) was established, the treatments with M. charantia or 45% alcohol (present as a vehicle in the drug) or saline were initiated at the rate of 0.2mg/kg b.w. orally once a day for 30 days.

Blood samples were collected from the marginal ear vein on 10th, 15th, 20th, 25th and 30th days of treatment for determination of blood sugar estimations and serum GH and PRL levels. All the blood sugar estimations were carried out on 12-hour fasted animals using a spectrophotometer. Serum GH and PRL concentrations were determined by chemiluminescence immunoassay.

Body weight lost and gained over per kg of initial body weight of each animal was recorded. For beta cells study, animals from each group were sacrificed and pancreatic tissues were dissected out.

Results
Administration of M.charantia at a dose level of 0.2ml/kg of b.w. for 30 days exhibited a fall in blood sugar; hypogylcaemic activity came into prominence after the 15th day of treatment. The fall in blood sugar value after drug treatment on the 20th day was significant (P<0.01) whereas on the 30th day was highly significant (P<0.001) when compared with the control groups of animals. The lowered elevels of GH and PRL associated with the alloxan treated rabbits were significantly increased due to treatment with M. charantia. The value of GH on the 20th day of treatment was P<0.05 and on the 30th day it was P<0.01. PRL concentration was increased on the 20th day, but significantly (P<0.01) elevated PRL level was recorded on the 30th day of the drug treatment as compared with control animals. Histopathological examination of the pancreas showed that the 30-day administration of M. charantia did not restore the beta cells of the islets of Langerhans which were destroyed by alloxan; there was no evidence of beta cell regeneration. However, viable beta cells of the islets of Langerhans were found to be more active and granulated on the drug treatment. The treatment with the drug helped in maintaining body weight whereas saline and vehicle failed to check weight loss. Discussion
From the data obtained, it is obvious that the administration of M. charantia caused a decrease in blood glucose level of alloxan-diabetic rabbits. The mother tincture of the drug produced a highly significant hypoglycaemic effect in animals with chemically induced insulin deficiency, whereas hypoglycaemia persisted throughout the experiment in the animals that received saline and vehicle.

It has been reported that sulphonylurea compounds produced hypoglycaemia in normal animals by stimulating the pancreatic beta cells to produce more insulin and by increasing the glycogen deposition in the liver. These drugs, however, do not decrease blood glucose in alloxan-diabetic subjects.9

In contrast to the oral anti-diabetic agents the exogenous administration of insulin is well known to produce hypoglycaemia in alloxan-diabetic subjects. It is therefore conceivable that hypoglycaemic principles in the M. charantia exert a direct effect in the diabetic rabbits, probably by a mechanism similar to insulin.

In the light of strong evidence that alloxan induces diabetes in laboratory animals,16 it is also clear from the diabetic control animals in this study that alloxan produced permanent hyperglycaemia by specific destruction of beta cells of islets of Langerhans. But the regular administration of M. charantia produced a significant fall in blood sugar, although the drug did not exhibit the restoration of the beta cells of islets of Langerhans. The viable beta cells which were found more active on the drug treatment provides evidence that M. charantia can stimulate the un-destroyed beta cells to enhance insulin secretion, decreasing blood glucose in diabetic animals. The possibility of M. charantia interacting with the beta cells of the pancreas is further supported by in-vitro studies.25

GH and PRL are polypeptides with similar amino acid sequences. As they share some biological activity they are grouped together as lactogenic hormones in the GH family. The regulation of GH and PRL gene expression and the pathway of GH and PRL synthesis are partly analogous.22 It is well established 4 and also clear in this study that increasing blood sugar levels in diabetic animals was accompanied by reduced GH and PRL. Exogenous insulin, even when administered after long term diabetes in rats partially/totally reversed these alterations, proving that they result from diabetes.27 Infusion of insulin does normalise the reduced GH secretion in diabetic rats.6 Under some circumstances insulin can stimulate GH gene expression in the rat pituitary gland in vitro10 and this stimulation could be lacking in the diabetic animals leading to reduced GH.

The data obtained in the Lucknow study showed that M. charantia treatment is able to increase GH and PRL levels in alloxan-induced hyperglycaemic rabbits, which is in close conformity with the findings of insulin infusion. It is therefore supposed that the existence of insulin-like molecules in M. charantia18 are capable of increasing GH and PRL secretions, probably by stimulation of somatotroph and lactotroph cells of the pituitary gland or on the hypothalamic cells.

Depite the fact that diabetic rabbits have virtually twice the food intake of normal rabbits, most of the calories in this food are not available to support body weight gain. In this study the administration of the drug daily for 30 days caused gain in body weight, which may also throw some light as the possible mechanism of hypoglycaemic activity either by direct stimulation of glucose uptake/utilisation or via the mediation of enhanced insulin secretion from existing beta cells.

References
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– condensed (and corrected) from the
Indian Journal of Homœopathic Medicine, vol 33/3, 2001