Hypoglycemic activity of C-glycosyl flavonoid from Enicostemma hyssopifolium.

Enicostemma hyssopifolium Verdoon (Gentianaceae) has been documented for various therapeutic effects in traditional systems of medicine; the hypoglycemic and hypolipidemic activities are also well reported. Bioactivity guided fractionation of methanol extract of E. hyssopifolium to test the hypothesis that E. hyssopifolium and its constituents influence cells and systemic glucose homeostasis. Derived fraction and isolated compounds were studied for (1) aldose reductase (AR) inhibition, (2) α-glucosidase inhibition, (3) effect on gluconeogenesis in rat hepatoma, (4) cytoprotection against streptozotocin (STZ)-induced toxicity on RINm5F cells, (5) normalization of glycemic control in acute hyperglycemic rat model, and (6) insulin-releasing effect both in vitro and in vivo. The results indicated that E. hyssopifolium can modify the glucose homeostasis at the cellular level. Two bioactive constituents were identified. Swertisin was found to inhibit AR (IC(50) 1.23 μg/mL) and α-glucosidase (IC(50) 1.89 μg/mL). It also possessed a significant cytoprotective action of RINm5F cell line against toxicant STZ. Swertiamarin was found to have hepatic gluconeogenesis inhibiting and insulin-releasing effect on rat hepatoma and RINm5F cells, respectively. The results of the in vivo study showed that swertiamarin, unlike the in vitro effect, produced no significant raise of insulin secretion. Swertisin normalized the serum glucose 60 min after high dose of glucose (2 g/kg, i.p.) in rats. These findings demonstrate that the fraction derived from the aerial part of E. hyssopifolium achieve normoglycemic status in hyperglycemic conditions via various mechanisms. The constituents swertiamarin and swertisin are responsible for bioactivity.