New olean-15-ene type gymnemic acids from Gymnema sylvestre (Retz.) R.Br. and their antihyperglycemic activity through α-glucosidase inhibition

Abstract A mixture of gymnemic acids was precipitated from the water extract of leaves of Gymnema sylvestre (Retz.) R.Br. ex Sm. (Asclepiadaceae) by acidification with 2 N H 2 SO 4 . The chromatographic separation of the mixture afforded five new gymnemic acids ( 1 - 5) . The compounds were characterized as Δ 15 oleanane glycosides on the basis of extensive spectral data analysis. The compounds ( 1 - 5 ) showed dose dependent inhibition of α-glucosidase, which was found to be comparable to acarbose (IC 50 95 μg/ml). Maximum inhibition was achieved with compound 4 (IC 50 57 μg/ml) followed by 3 (IC 50 62 μg/ml), 1 (IC 50 80 μg/ml), 2 (IC 50 120 μg/ml) and 5 (IC 50 128 μg/ml). The results revealed that the overall pattern of hydroxyl and acyl substitutions of compounds affected their inhibitory activity. In oral sucrose tolerance test, pre-treatment with crude gymnemic acid mixture and isolated compounds 1 and 4 at a dose of 10 mg/Kg b.w. significantly blunted the effect of sucrose challenge in mice. Based on these results, the antihyperglycemic effect of G. sylvestre can be, at least partly, attributed to the inhibition of α-glucosidase by its gymnemic acids. The current study provides relatively more direct evidence explaining the effectiveness of G. sylvestre against hyperglycemia.