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As part of our effort to discover new α-glucosidase inhibitors from natural sources, it was found that an aqueous extract from Melampodium perfoliatum (Cavanilles) Kunth (Asteraceae) inhibited the activity of rat-intestinal α-glucosidases in a concentration dependent manner (IC 50 = 958 μg/mL). Fractionation of the active extract led to the isolation of perfoliatin A (1), which was active against the mammal α-glucosidases and a recombinant α-glucosidase with maltase-glucoamylase activity obtained from Ruminococcus obeum. Kinetic analysis revealed that the interaction of 1 with R. obeum-α-glucosidase was noncompetitive. The calculated Ki was 0.68 ± 0.034 mM. In vivo testing using an oral sucrose tolerance test, in healthy and hyperglycemic mice, revealed that perfoliatin A (1) reduced significantly the postprandial peak, consistent with its α-glucosidase inhibitory activity. The effect was comparable or better to that of acarbose, a therapeutically used α-glucosidase inhibitor. Altogether, these findings clearly supported the α-glucosidase inhibitory activity of melampolide-type of sesquiterpene lactones.

In Vivo and In Vitro α-Glucosidase Inhibitory Activity of Perfoliatin a from Melampodium Perfoliatum