Type 2 diabetes mellitus (T2DM) and its associated complications represent a significant public health issue affecting hundreds of millions of people globally; thus, measures to prevent T2DM are urgently needed. Chuju has been proven to possess antihyperglycemic activity. However, the bioactive ingredients in chuju that contribute to its antihyperglycemic activity, as well as the relationship between its antihyperglycemic activity and the gut microbiota, remain unclear. To understand the potential effects that it has on T2DM, the glycolipid metabolism and gut microbiota regulation of flavonoid-rich extracts from chuju (CJE) were investigated. The results showed that the top ten flavonoid compounds in CJE are Apigenin 6, 8-digalactoside, Apigenin 6-C-glucoside 8-C-arabinoside, Luteolin-4′-O-glucoside, Isoshaftoside, Scutellarin, Quercetin 3-O-malonylglucoside, Chrysoeriol 7-O-glucoside, Quercetin-3,4′-O-di-beta-glucoside, Luteolin 6-C-glucoside 8-C-arabinoside, and Homoorientin. Furthermore, CJE mitigated hyperglycemia and glycolipid metabolism by reducing the abundance of Faecalibaculum, Coriobacteriaceae, and Romboutsia and increasing the abundance of Alistipes. In addition, the results of Western blot analysis showed that CJE could enhance glycogen synthesis and glucose transport by up-regulating the phosphorylation of IRS1-PI3K-Akt and AMPK-GLUT4. Simultaneously, CJE could decrease gluconeogenesis by down-regulating the phosphorylation of FoxO1/GSK 3β. In conclusion, the findings of this study provide new evidence supporting the hypothesis that CJE can be used as part of a therapeutic approach for treating disturbances in glycolipid metabolism via regulating the gut microbiota and mediating the IRS1-PI3K-Akt-FoxO1/GSK 3β and AMPK-GLUT4 pathways.

The prevention of type 2 diabetes mellitus (T2DM) and its associated complications is an urgent public health issue that affects hundreds of millions of people globally. Chuju has been proved to possess antihyperglycemic activity. However, the bioactive ingredients in chuju that contribute to antihyperglycemic activity as well as the relation between its antihyperglycemic activity and gut microbiota remain unclear. To understand the potential effect it has on T2DM, the glycolipid metabolism and gut microbiota regulation of flavonoids-rich extracts from chuju (CJE) were investigated. The results showed that CJE remarkably mitigated hyperglycemia and glycolipid metabolism by regulating the gut microbiota in T2DM mice. Furthermore, the macro-genome sequencing results showed that CJE intervention regulated the composition of gut microbiota in T2DM mice, characterized by downregulating the abundance of Faecalibaculum, Coriobacteriaceae, Romboutsia and up-regulating the abundance of Alistipes. In addition, CJE could promote glycogen synthesis, gluconeogenesis, glucose transport and inhibite glycolysis by regulating the expression of insulin-mediated IRS1-PI3K-Akt-FoxO1/GSK 3β pathway and non-insulin-mediated AMPK-GLUT4 pathway. Taken together, the results provided new evidence that CJE alleviate disturbance of glycolipid metabolism via regulating gut microbiota and mediating IRS1-PI3K-Akt-FoxO1/GSK 3β, AMPK-GLUT4 pathway.