Hypericum attenuatum Choisy, as an edible medicinal plant, possesses multiple therapeutic effects. Type 2 diabetes is a metabolic disorder that has become a major threat to public health. The objective of this study was to investigate the hypoglycemic effect of Hypericum attenuatum Choisy extracts (HaC) on T2DM mice and modulatory effect of HaC on composition of intestinal microflora. T2DM mice were treated with HaC for 5 weeks. HaC could modulate fasting blood glucose, improve hepatic insulin sensitivity and promote hepatic glycogen storage by activating IRS1/PI3K/AKT pathway. Moreover, HaC regulated dysfunctional lipid metabolism and reduced inflammation in T2DM mice. Additionally, HaC treatment could modulate the compositions of gut microbiota in small intestine and colon with the altered abundances of Firmicutes , Bacteroidetes and Proteobacteria . Meanwhile, HaC treatment could augment short chain fatty acids contents. These results demonstrate that H. attenuatum Choisy may be a potential therapy for the treatment of T2DM.
Hypericum attenuatum Choisy is a traditional Chinese herbal plant with multiple therapeutic effects. In this study, bioactivity-guided fractionation of Hypericum attenuatum Choisy extracts afforded three major flavonoids (including astragalin, guaijaverin and quercetin), which possessed α-Glucosidase inhibitory activity with IC 50 values of 33.90±0.68 μM, 17.23±0.75 μM and 31.90±0.34 μM, respectively. Circular dichroism analysis revealed that all the three compounds could interact with α-glucosidase by inducing conformational changes of the enzyme. Molecular docking results indicated that they could bind to the active site in α-glucosidase, and the binding force was driven mainly by hydrogen bond. Additionally, isobolographic analysis of the interactions between two compounds showed that all the combinations presented a synergistic α-glucosidase inhibitory effect at lower concentrations, and the combination between quercetin and guaijaverin or astragalin exhibited the best synergistic effect. This research might provide a theoretical basis for the application of Hypericum attenuatum Choisy in treating hyperglycemia.