Antihyperglycemic Effects of Gymnemic Acid IV, a Compound Derived from Gymnema sylvestre Leaves in Streptozotocin-Diabetic Mice

Abstract We investigated the antihyperglycemic action of a crude saponin fraction and five triterpene glycosides (gymnemic acids I–IV and gymnemasaponin V) derived from the methanol extract of leaves of Gymnema sylvestre R. BR. (Asclepiadaceae) in streptozotocin (STZ)-diabetic mice. The saponin fraction (60mg/kg) reduced blood glucose levels 2–4 h after the intraperitoneal administration. Gymnemic acid IV, not the other 4 glycosides at doses of 3.4–13.4 mg/kg reduced the blood glucose levels by 13.5–60.0% 6 h after the administration comparable to the potency of glibenclamide, and did not change the blood glucose levels of normal mice. Gymnemic acid IV at 13.4 mg/kg increased plasma insulin levels in STZ-diabetic mice. Gymnemic acid IV (1 mg/mL) did not inhibit α-glycosidase activity in the brush border membrane vesicles of normal rat small intestines. These results indicate that insulin-releasing action of gymnemic acid IV may contribute to the antihyperglycemic effect by the leaves of G. sylvestre. Gymnemic acid IV may be an anti-obese and antihyperglycemic pro-drug.