Inhibition mechanism of α-glucosidase inhibitors screened from Artemisia selengensis Turcz root

Abstract

Artemisia selengensis Turcz root (ASTR) is a potential material for screening natural α-glucosidase inhibitors, which effectively reduce postprandial blood glucose level. In this study, natural α-glucosidase inhibitors were screened, and their inhibition mechanism was investigated. Six compounds, including 3,5-dicaffeoylquinic acid (1), 3-caffeyl-5-feruloylquinic acid (3,5-CFQA) (2), 1,3-dicaffeoylquinic acid (3), chlorogenic acid (4), 4-caffeoyl-5-ferulylquinic acid (5) and 3,5-dicaffeoylquinic methyl ester (6), were screened from ASTR through bioactivity-guided isolation. Compounds 2, 5 and 6 were identified from Artemisia selengensis Turcz (AST) for the first time. Given that 3,5-CFQA possessed better inhibitory effect and exhibited considerably lower IC50 value (289.96 μM) than acarbose (600.37 μM), its inhibitory mechanism was investigated. Results showed that 3,5-CFQA reversibly inhibited α-glucosidase activity in a one-way kinetic process through a mixed-type mechanism. The interaction was mostly driven by van der Waals force and hydrogen bonding. The formation of the 3,5-CFQA-α-glucosidase complex involved static quenching and exothermic reaction, which induced the conformational changes in α-glucosidase. Only one class of binding site was found. The results of this work suggested the potential of 3,5-CFQA in inhibiting α-glucosidase activity.