Antidiabetic activity of the ethyl acetate fraction of Ficus lutea (Moraceae) leaf extract: Comparison of an in vitro assay with an in vivo obese mouse model

Abstract

Background: Ficus lutea crude acetone leaf extracts were previously shown to stimulate glucose uptake and insulin secretion of established cells and, inhibit α-amylase and α-glucosidase activities. Methods: For this study, F. lutea acetone extracts were subjected to solvent-solvent fractionation to yield fractions with differing polarities (hexane, chloroform, dichloromethane, ethyl acetate, n-butanol and water) in an attempt to obtain a more potent fraction with in vitro and probably in vivo activity. Results: Among these fractions, the ethyl acetate fraction had the highest total polyphenol content (100.5 ± 1.6 mg GAE/g dried extract) and α-glucosidase inhibitory activity (126.8 ± 30.6 μg/ml). It also stimulated the highest glucose uptake of C2C12 muscle cells and decreased extracellular glucose concentration of H-4-II-E liver cells with low cytotoxic activity. The ethyl acetate fraction (10.88 ± 0.55 μg/L at 250 μg/ml) enhanced insulin secretion in RIN-m5F pancreatic β-cells to the same degree as the positive control glibenclamide (11.09 ± 0.07 μg/L at 1μM). While fractionation increased α-glucosidase inhibition and glucose uptake of cells, in the ethyl acetate fraction, the α-amylase inhibition and insulin secretion decreased. The weight reducing and glucose control potential of the ethyl acetate fraction in an obese mouse model, important factors in the amelioration of type II diabetes was determined. The extract had no statistical significant weight reducing activity. Conclusion: A major finding was the decrease in the area under the curve of the glucose concentration over time in animals that were treated with both a change in diet and with the plant extract. This is linked to increased glucose uptake within the cells, the most likely mechanism is either an increased insulin response or increased insulin secretion.