Baicalein improves liver inflammation in diabetic db/db mice by regulating HMGB1/TLR4/NF-κB signaling pathway

The current study was designed to investigate the hepatoprotective effects and possible mechanisms of Baicalein (BA) on the diabetic liver injury in vivo and in vitro. The results exhibited that BA significantly restored the blood glucose in oral glucose tolerance test (OGTT) and inhibited the levels of insulin, alanine aminotransferase (ALT), aspartate aminotransaminase (AST), total cholesterol (TC) and triglyceride (TG) in C57BL/KsJ-db/db mice. Moreover, BA strikingly attenuated the extent of steatosis in the liver tissues of diabetic mice. These results confirmed the hepatoprotective effects of BA on diabetic liver injury. Further in vivo investigations revealed that the hepatoprotective activities of BA was due to the effects on remarkably suppressing the inflammatory cascade, including attenuating the expressions of HMGB1, TLR4, Myd88, NF-kappa B and I kappa B proteins and inhibiting the production of interleukin (IL)-1 beta, IL-6 and tumor necrosis factor (TNF)-alpha in diabetic mice. Finally, the hepatoprotective effects of BA were characterized in human hepatic HepG2 cells. With response to palmitic acid challenge, increased amount of insulin, ALT, AST, TG, TC were observed, whereas BA pretreatment significantly restored these changes in HepG2 cells. Inflammation condition was also recovered with BA treatment as shown by the changes of HMGB1, TLR4, Myd88, NF-kappa B and I kappa B expressions and the levels of IL-1 beta, IL-6 and TNF-alpha. These findings elucidated that BA exhibited prominent hepatoprotective activities in diabetic live injury.