ANTI-HYPERGLYCEMIC POTENTIAL OF STANDARDISED ETHANOLIC EXTRACT FROM NEPHELIUM LAPPACEUM RIND

Abstract

Diabetes mellitus is a chronic metabolic disease and predicted to increase about 366 million cases globally by end of 2030. Type 2 Diabetes is characterized by abnormal insulin secretion followed by inability of beta cells to compensate for insulin resistance. Most individuals diagnosed with diabetes are found to be obese and obesity as well is one of the major risk factors contributing to diabetes. Although modern medicine is used to control blood glucose level in diabetic patients but there is demand for natural products as anti-diabetic agents due to the side effects seen in the current drugs. In this study, we explore Nephelium lappaceum.L’s (or locally known as rambutan rind) ability as an anti-hyperglycemic agent in a type 2 diabetic animal model. The rind of N. lappaceum is found to consist of high antioxidant activity and possess in-vitro anti-hyperglycemic activity. This study is aimed initially to prepare standardised ethanolic extracts of N. lappaceum rind, evaluate toxicity effects in rat model, develop obesity induced type 2 diabetes rat model and finally investigate the anti-glycemic effects of Nephelium lappaceum rind in the diabetic rat model. Ethanolic extraction was followed as previously described to obtain N. lappaceum rind extract. Geraniin being the major bioactive compound in N. lappaceum rind was detected in LC/MS and quantified using HPLC chromatogram method to ensure a standardised sample was prepared. Biological standardisation was also carried out by subjecting the N. lappaceum rind to both alpha glucosidase and alpha amylase assay’s and to establish its in-vitro anti-hyperglycemic activity. Toxicity studies of N. lappaceum rind were carried out in Sprague dawley rats. In the acute toxicity study, rats were given 50mg, 200mg, 1000mg and 2000mg/kg of N.lappaceum rind orally for 14 days whereas in the sub-chronic toxicity study the rats were given a low and high concentration of N. lappaceum rind for 28days (500mg and 2000mg/kg). Type 2 diabetes was seen to develop in the rat model by feeding them with a high fat diet for 12 weeks and injected with 55mg/kg streptozotocin and 210mg/kg nicotinamide. Then, the diabetes induced rats were treated with N. lappaceum rind at 500mg and 2000mg concentrations for 28 days. Positive control rats were treated with 200mg metformin. In this study, we obtained a 41.06% yield of ethanolic extracts from powdered N. lappaceum rind, while geraniin present in the extract was quantified at 33.0 ± 0.2 mg geraniin/g extract. N. lappaceum rind did not show any toxic effect in the rats both during acute and sub-chronic toxicity study. All biochemical analysis, histology of organs, body weight and relative organ weight clearly showed that there were no significant changes in treated rats. Our study also revealed that, the diabetes induced rats treated with 2000mg N. lappaceum showed reduction in blood glucose level and improved insulin levels which were similar to metformin treated group. Pancreas histology revealed that, the group treated with 2000mg of N. lappaceum had a good distribution of healthy islets and the treatment is comparable to the effect of metformin-treated group. Immunohistochemical staining with Glut-4 and PPAR-gamma antibody also markers for regeneration was over expressed in N. lappaceum treated group with large regenerating islets and the effects were similar to metformin-treated group. In conclusion, N. lappaceum rind extract was able to display anti-hyperglycemic activity at a dose of 2000mg/kg without any toxic effects in high fat diabetes-induced rats.