Modulation of gut microbiota and hypoglycemic/hypolipidemic activity of flavonoids from the fruits ofLycium barbarumon high-fat diet/streptozotocin-induced type 2 diabetic mice

Lycium barbarum has been used as a traditional medicinal and edible plant in China. The fruits of L. barbarum, rich in flavonoids with large exploration potential, are associated with antioxidant and anti-inflammatory activities that may contribute to reducing the risk of diabetes. However, information on the antidiabetic activity of flavonoids from L. barbarum (LBFs) is still limited. In this study, therefore, the effects of LBFs on the high-fat diet (HFD)/streptozotocin (STZ)-induced type 2 diabetes (T2DM) mice were investigated. LBFs showed significant anti-diabetic activity, as evidenced by the recovery of various physical signs (body weight and the level of GLP-1 were increased and water consumption, liver index, fasting blood glucose, HOMA-IR, HOMA-IS, levels of HbA1c, and OGTT were decreased), improving the function of glucose and lipid metabolism (levels of TC and TG in the serum and liver were decreased, mRNA expression of GK, PFK and PPARα were increased, and mRNA expression of G6Pase, PEPCK, PPARγ, FAS, ACC, and SREBP-1c were inhibited), reduction of the expression of proinflammatory cytokines and related mRNA (such as LPS, TLR-4, TNF-α, IL-6, IL-10, and IFN-γ), and restoration of liver tissue structure (characterized with reduction of fat vesicles, remission of hepatocyte swelling, and orderly arrangement of hepatic cords). Moreover, the modulation of gut microbiota of HFD/STZ-induced T2DM mice was explored. The results showed that Bacteroidales_S24-7_group, Lachnospiraceae, Ruminococcaceae, Clostridiales_vadinBB60_group, Allobaculum, Turicibacter, Coriobacteriaeceae and Enterococcus were the dominant bacteria associated with T2DM. In conclusion, LBFs ameliorated HFD/STZ-induced T2DM in mice through three targets, including improving glucose and lipid metabolism, blocking pro-inflammatory cytokines, and regulating gut microbiota, except that the optimal dose of LBFs needs to be further explored.