Author: Y. Srivastava, H. Venkatakrishna-Bhatt, Y. Verma
Type of Publication: Pre-Clinical
Date of Publication: 1988
Publication: Pharmacological Research Communications Vol. 20 No. 3 pp 201-209,
1988
Organization/s: B.J. Medical College, National Institute of Occupational Health
Abstract: The fruit extract of Momordica charantia Linn. was studied in Charles
Foster rats of both sexes in respect of its dose-response hypoglycemia and at maximal effective dose, its influences on the development of diabetic cataract.
Alloxan (120 mg.kg s.c./rat, single dose) diabetic rats with 150 mg% of blood sugar were classified into four groups ( n= 10) wherein two control and rest were test groups). In the test group, the oral dose response hypoglycemic herbal effect was found to be maximum at 4 g/kg/Day/rat when administered for 20 days. This dose was continued in the 2 nd test group for a period 2 months. Blood sugar in all the rats were estimated by microdetermination method using a dextrometer before and after therapy. The control group of rats received 2 ml of 0.9% NaCl and they developed cataract in 90 to 100 days. The herbal treated diabetic showed cataract in 140 to
180 days. Cataract formation was found to be dependant on blood sugar levels since the control group with blood sugar 307  81 (mg%) was blind 2 months earlier than herbal treated roup which showed blood sugar 149  66.37 (mg%).
EFFECT OF MOMORDICA CHARANTIA LINN. POMOUS AQUEOUS EXTRACTION
( missing text ) IN MURRIN ALLOXAN DIABETICS ( missing text ) H, Venkatakrihna-
Bhatt ** and Y. Verma *** Department of Biochemistry*, B. J. Medical College,
Asarva and Division of Agricultural Health ** & Aquatic Toxicology ***, National
Institute of Occupational Health, ( ICMR), Meghani Nagar, Ahmedabad 380016 (
Gujarat) India.
Introduction
The fruit bitter-gourd (Momordica charantia Linn.) is folklore medecine in rheumatism, gout, dismenorrhea, leprosy, piles, jaundice, liver and spleenb disorders
(Nadakarni, 1927). It induce hypoglycemia (Rivera, 1941, 1942; Sharma, Sogani and Arrora, 1960) and its active principal, a protein (vegetable insulin) is homologous to human insulin (Khanna, Nag and Jain, ( missing text ) Baldwa,
Bhandari, Pangaria and Goyal, 1977). The seeds of this plant show hypoglycemic activity comparable to glypenclamide (Kedar and Chakravarti, 1982). The vegetable insulin was found orally effective (Khanna, 1985). Diabetic were healthy when they consumed herbal fruit (Vad, 1959) and hypoglycemic (even with raw fruits) (
Upadhyaya, 1959). The fruit extract was administered p.o. in rats (Gupta, 1962) and rabbits ( Yaqub, 1980) and its hypoglycemic activity was confirmed.
Retinopathy and neuropathy were recognized as specific complications of diabetes (Rober, Bradley and Ramos, 1973). Not only diabetics receive insulin, but also person with lesser degree of hypoglycemia opt insulin (Cecil, 1970). Patients

with high blood sugar are susceptible for diabetes and suffer from impaired glucose tolerance which is a preclinical marker of diabetes (Srivastava, Venkatakrishna-
Bhatt, Verma and Prem, 1987). Increased coagulation activities in diabetics
(Srivastava, Pandya, Patel and Gupta, 1985) may contribute to the development of retinopathy (Stevens, Roazer, Monnier and Cerami, 1978) and Momordica charantia may delay this anomaly. The goal of this study is to find maximal effective hypoglycemic effect of herbal extract and its ameliorating potential in cataractogenesis as a supporting evidence of its antidiabetic property.
Materials and Methods
The Charles Foster rats of both sexes weighing 150-200 g. red with standard laboratory diet (consisting of 70% cracked wheat, 20% cracked bengal gram, 5% fishmeal, 4% yeast powder, 0.5% groundnut oil and 0.5% shark liver oil in the form of dry mash) and ad libitum water were used in this study. Overnight fasting rats were s. c. injected with fresh alloxan (120 mg/kg body-weight in 0.9% NaCl). The blood sample was drawn by pinch-clip method from caudal vein. Blood sugar was determined with dextrometer (Miles India Ltd.) before fasting and 36 hour after alloxan administration. Rats showing blood sugar levels of 150 or more (mg%) were marked diabetic. Two such rats/cage were maintained under uniform animal husbandry and climatic conditions (27-32 o C). Unviable rats ror alloxan and experimental set up were discarded.
The fresh fruit extract was prepared by chopping into small pieces and boiled in 150 ml of water at low flame (65 o C) till its volume reduced to 50%. The extract was then cooled and diluted with distilled water as per the volume/dose to be fed.
Two ml of extract/Day/rat was administered (force feeding) by oral intubation.
The rats were divided (10 each) into groups; a control set (placebo) received
2 ml of saline experimental set received once a day/rat, 2 ml of extract for a period of two months even after maximal effective dose. Blood sugar in controland experimental diabetic sets, fundus, lenticular opacities, opthalmoscopy, signs and symptoms were examined periodically in these animals. The test of significance is calculated by employing simple student ‘t’ test comparing and test groups.
Results and Discussion
Table I shows the maximal hypoglycemic effect at dose of 4 g/Day/rat of
Momordica charantia acqueous fruit extract in alloxan diabetic rats. The hypoglycemic agent in the extract was reported to have been the vegetable insulin, which was further identified as a polypeptide P culture method (Khanna, Nag, Jain,
1974) and found analogous to human insulin.
The average period of apparent diabetic cataract in alloxan injected rats found to be around ( Table 2 ) while such a development in herbal treated diabetic rat was found to be around five months and this delayed cataract formation was statiscally significant (P  0.01). The blood sugar in the herbal treated diabetic group remained lower unlike the diabetic control group.
Diabetes mellitus is a disease best characterized by chronic hyperglycemia of manifold aetiology. Acute symptoms may be thirst, polyurea, weight loss and can progress to lethal ketoacidosis and coma. Further sublethal effects are pruritis valves, balanitis, skin infections, unsual fatigue and visual impairment. Many of these effects we did find in the diabetic control rats.
Prevention or delaying senile cataract has been by early diagnosis and treatment of diabetes with insulin and diet control since hyperglycemia per se could be a primary factor by a change in stucture and lens metabolism causing ocular

opacity (Rober, Bradley and Ramos, 1973). Insulin therapy in jevunile diabetics prevented acute metabolic disorders (ketoacidosis etc.), yet certain hyperglycemic related sequelae (retinitis, neuropathy, renal glomerulosclerosis) appeared (Cecil,
1979). Therefore, the role and treatment of diabetes by herbal extracts of hypoglycemic property and such related disorders emphasizing role of high blood sugar in diabetic complications. Henceforth, a drug-response study of the herbal fruit extract was carried out to in alloxan diabetic rats to find out its maximal effective dose in respect of reduction of blood sugar in them.
The blood sugar index is a common variable used to defin diabetes but even if abnormalities of glucose metabolism were first to be studied, they are not sole pathologic manifestation nor have they been proved beyond doubt to be the first pathologic sequelae. The chronic hyperglycemia may be asymptomatic but is generally recognized as a predisposing factor for specific microvascular complication namely retinopathy and neuropathy (Dorn, Rhymes, Cedarholm, Williams, Rizza,
Pebys and Turner, ’83).
The retinopathy is one the most frequent complication of diabetes mellitus.
There is a clinical recognition of cataract as a diabetic complication. Its incidence and severity increases with advancement of disease and approximately 1.5-6% diabetics show blindness due to retinopathy (Rober, Bradley, and Ramos, 1973).
Recent developments in protein chemistry suggest a unique pathochemical hypothesis for the long term diabetes mellitus. Under normal physiological conditions, glucose can react non-enzymatically with proteins to form stable covalent adducts while can undergo further rearrangements to form brown fluorescent pigments which can cross link-proteins. It is suggested that these reactions take place in vivo at an accelerated rate in diabetic sequelae (Srivastava, Venkatakrishna-
Bhatt, Nigam, Jhala, Verma and Prem, 1985).
The body proteins that are exposed to higher glucose concentration are affected by glycosylation. Stevens, Roozer, Monnier and Cerami (1987) showed that uptake of glucose by bovine lens protein was accompanied by opacifications.
Monnier, Stevens and Cerami (1979) have demonstrated disulfide linked high molecular weight protein aggregates are responsible for the formation of cataract.
Though these reactions take place in vivo yet the Monnier (1979) group proposed the non-enzymatic browning of lins proteins might have involved in cataract formation. Since these reactions also occur with aging of proteins, the explanation offered provides an answer for the lens discolouration in human diabetes.
The common advocated treatment in diabetes include oral antidiabetic tablets like pluriform and sulfonylurea compounds and injectables like insulin. Though these treatment alleviate ailment temporarily and may prolong life-span yet they pose adaptation problems. Despite of a check of rising blood sugar level, secondary complications of diabetes appear as usual with lapse of time (cecil, 1979). Hence always there had been search for a treatment of diabetes which might have blood sugar lowering properties (Srivastava, Venkatakrishna-Bhatt, Jhala, Nigam, Asok-
Kumar and Verma, 1986) with better adaptation so that the body functions as a whole to face this dreadful disease. It has been found that herbs inaddition to lowered blood sugar in hyperglycemic subjects, serve as adaptogens by ameliorating symptoms due to nueropathological disorders (Srivastava, Venkatakrishna-Bhatt,
Gupta, 19830 and their effect as evaluated in terms of blood sugar which persisted even in discontinuation of treatment (Srivastava, Venkatakrishna-Bhatt, Jhala,
Nigam and Ashok-Kumar, 1985). The hypoglycemic property of fruit extract of
Momordica charantia is well established and confirms the earlier observations
(Sharma, Sogani, and Arora, 1960; Baldwa, Bhandari, Pangaria and Goyal, 1977;
Kedar and Chakrabarti, 1982 and Pugazhenitha and Suryanarayana, 1979). In this study, diabetic cataract was selected as a criterion to evaluate the adaptogenic and

antidiabetic properties of the herbal medecine. According to Jones and Cerami
(1985), exposure to higher concentration of glucose (as in diabetes) leads to nonenzymatic glycosylation of lens proteins which probably causes the opacity and cataract. Reduction of blood sugar in Momordica charantia treated rats is probably the reason for delayed appearance of cataract (Srivastava, Venkatakrishna-Bhatt,
Nigam and Prem, 1986).
Acknowledgements
The authors wish to thak Professor B. B. chatterjee, Ex-Director, National
Institute of Occupational Health and the Dean, B. J. Medical College, Ahmedabad for support and encouragement during this study.
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