Taxifolin Attenuates Hepatic Fibrosis and Injury in High-Fat Diet and Streptozotocin-Induced Type 2 Diabetes Mice

This study investigated the protective effects of taxifolin (TAX), a bioflavonoid, against hepatic fibrosis and injury in the type 2 diabetes mellitus (T2DM) mouse model. T2DM model was induced in male C57BL/6 mice by high-fat diet (HFD) and intraperitoneal injection for 5 consecutive days of 40 mg/kg streptozotocin (STZ). HFD-STZ groups were administered TAX (80 mg/kg/day) or vehicle daily for 12 weeks. The control or wild-type (WT) group received equal amounts of the vehicle and was fed a normal chow diet. Body weight and blood glucose were checked every 4 weeks. H&E and Masson's trichrome staining were performed to assess liver fibrosis and injury. The western blot was used to determine the expression levels of key fibrotic proteins. The data showed that taxifolin treatment significantly decreased body weight, liver weight, and blood glucose in diabetic mice. In particular, liver enzymes including alanine transaminase (ALT) and aspartate transferase (AST), and triglyceride levels were significantly higher in the non-treated diabetic group than in the WT group but markedly reduced after TAX treatment. In addition, the histological analysis revealed that TAX attenuated hepatic interstitial fibrosis. Moreover, western blot data showed downregulation of fibrotic markers including TGF-β1, Col1a1, and Smad2 in TAX group treatment indicating the molecular mechanisms through which TAX exerts its hepatoprotective effects. These findings suggest that TAX holds therapeutic potential in mitigating liver fibrosis and injury associated with T2DM, providing a promising avenue for further research and potential clinical application.