Due to the high incidence of diabetes and its associated complications, diabetes is widely recognized as a serious global health problem. In diabetes treatment strategies, targeting α-glucosidase, a key carbohydratehydrolyzing enzyme, has emerged as a highly regarded approach. To develop novel α-glucosidase inhibitors, we successfully synthesized a series of apigenin analogs, collectively referred to as H1-H27 compounds and examined their inhibitory effects on α-glucosidase activity. H7 showed a remarkable inhibitory effect, surpassing that of the standard drug acarbose. Further analysis revealed that H7, H10, and H24 act as non-competitive inhibitors of α- glucosidase. In vivo experiments using a type 2 diabetes mouse model demonstrated the diverse therapeutic potential of H7; it effectively lowered blood sugar levels, improved glucose tolerance, and corrected lipid metabolism. In addition, H7 showed hepatoprotective effects, highlighting its ability to improve liver function. H7 also positively influenced the gut microbiota composition in diabetic mice, increasing diversity and richness. These results highlight the promising therapeutic effects of apigenin analogs, such as H7, for treating type 2 diabetes and show how they could provide numerous benefits, including effective inhibition of α-glucosidase, improved glucose control, correction of lipid metabolism, hepatoprotection, and modulation of the intestinal microbiota.
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