Investigation on the inhibition mechanism and binding behavior of cryptolepine to α-glucosidase and its hypoglycemic activity by multi-spectroscopic method

Abstract

Cryptolepine, one important active ingredient of Cryptolepis sanguinolenta (Lour), exhibits various beneficial pharmacological activities. But its anti-α-glucosidase and hypoglycemic activities are still not cleared. Thence, in this study, we investigated its inhibitory effects on α-glucosidase by a multi-spectroscopic method and in vivo hypoglycemic activity by the oral glucose tolerance test (OGTT). The results showed that cryptolepine is a reversible mixed-type α-glucosidase inhibitor with IC50 value of 0.44 ± 0.05 mM, ∼ 2-fold stronger than positive control acarbose (IC50: 0.72 ± 0.02 mM). Fluorescence quenching confirmed cryptolepine could quench the endogenous fluorescence of α-glucosidase in a static process. Fluorescence quenching, synchronous fluorescence, CD spectra, and 3D fluorescence results showed that the binding of cryptolepine with α-glucosidase caused chromophore microenvironment and conformation changes of α-glucosidase, consequently inhibiting its catalytic activity. Molecular docking revealed the detailed binding interactions between cryptolepine and α-glucosidase. Furthermore, oral administration of cryptolepine could improve the glucose tolerance in mice to reduce the postprandial hyperglycemia. These findings provide a solid foundation for understanding the inhibitory effects on α-glucosidase and hypoglycemic activity of cryptolepine.