Toxicity, Acute and Longterm Anti-Diabetic Profile of Methanolic Extract of Leaves of Pterocarpus Marsupium on Alloxan Induced Diabetic Albino Rats
Behara Chandra Rekha, Sunitha Tangeti, LankeVenu Madhavi, Rama Mohan Pathapati
Background- Type-2 Diabetes becomes a real problem of public health in developing and developed countries, where its prevalence is increasing gradually, and suitable treatment is becoming expensive. It is also multifactorial ailment leading to numerous complications, which in turn demands alternative therapeutic approach in view of side effects like hypoglycemia, weight gain, gastrointestinal disturbances, and liver toxicity caused by present drugs available drugs in the market. Conventionally antidiabetic effect of some herbal extracts has been confirmed in human and animal models of type 2 diabetes as an alternative medicine/nutritional supplements. To this rationale, we studied the antidiabetic effect of methanolic extract of leaves of Pterocarpus marsupium on alloxan induced diabetic albino rats. Methods- Albino rats of Wister strain weighing 180 – 225 gm of either sex, non-pregnant were used for the study, were procured from our animal house. We employed Alloxan monohydrate 5% fresh solution (125mg/kg body weight) administered intraperitoneally to induce diabetes. Animals were divided into four groups with six animals in each group, kept separately in different cages. Group N: - Non-diabetic rats served as control group and received plain water, Group C: -Diabetic control group (Alloxan +2% Gum Acacia), Group G: -Standard group (Alloxan +0.5mg/kg BW Glibenclamide) and Group PM: -Test group (Alloxan +700mg/kg BW Pterocarpus marsupium leaves). Acute toxicity study was conducted using doses 100-1000 mg/kg body weight of Pterocarpus marsupium on healthy rats, additionally; 24-hour antidiabetic profile was also conducted on animals of four groups. In 6th-week efficacy study after giving the medications under trial, fasting blood glucose levels were recorded on the 1st, 3rd, 7th, 14th, 21st, 28th, 35th&42nd Day. On 42nd day biochemical parameters such as total protein, serum albumin, albumin to globulin ration, Total cholesterol, LDL VLDL, HDL and LDL/HDL ratio were also analysed. After six weeks of study, two animals from each group were sacrificed & the animals were dissected & their pancreas was sent for histopathological examination. Results-700mg/kg body weight Pterocarpus marsupium leaves showed its peak action in 24-hour anti-diabetic activity and also was found to be safe in acute toxicity study. For this reason, the therapeutic dose for hypoglycemic activity was calculated as 700mg/kg. In 24 Hour antidiabetic study with methanol extract of leaves of Pterocarpus marsupium on alloxan induced diabetic rats: After administration of 700mg/kg methanolic extract of Pterocarpus marsupium leaves, we observed the fall in blood glucose concentrations were 56.12% at a 1st hour & 14.61% at a 2nd hour with (p <0.0001). The maximum percentage reduction in fasting blood glucose value was achieved at 24 hrs., indicates the long acting nature of the extract (i.e.,) >24 hrs. In 42-day study, the percentage reduction in blood glucose with 700mg/kg body weight of the extract was, 14.51%, 50.16%,42.12%,44.49%,52.23%,56.48%,53.26% and 56.32% on 1, 3, 7, 14, 21, 28, 35 & 42 days respectively. Whereas with Glibenclamide it was 40.29%,42,51%, 38.98%,40.10%, 43.49%, 40.39%, 42.24% & 47% on 1, 3, 7, 14, 21, 28, 35 & 42 days respectively. On 42nd day Pterocarpus marsupium showed reduction in total cholesterol (54.51%), LDL cholesterol (58.86%), LDL/HDL ratio (80.47%) and albumin/globulin ratio (63.82%) (p<0.05), suggesting its statistical significance on comparison with Glibenclamide which show a marginal raise in above parameters Such as total cholesterol (4.65%), LDL cholesterol (4.35%) & LDL/HDL ratio (10.31%) and albumin/globulin ratio (3.89%) Such a result explains that, in such a long term significant antihyperglycemic activity we observed reductions in the biochemical parameters by the methanol extract apart from their improvement in diabetes. Conclusion- The above results indicate that methanol extract of leaves of Pterocarpus marsupium plant has significant & sustained oral hypoglycemic activity, comparable with the oral hypoglycemic effect of insulin secretagogue like glibenclamide, a sulphonylurea. Hence, it is concluded, that this antidiabetic effect may be due to increased secretion of insulin. Even it showed significant improvement in lipid profile, serum Albumin/Globulin ratio and beta cell regeneration; still it needs larger studies to confirm.