Sinensetin Ameliorates Lipopolysaccharide-Induced Liver Injury by Targeting the TLR4/NF-κB/NLRP3 Pathway and Related Gut–Liver Axis Dysfunction in Mice

Sinensetin is a multimethoxy flavonoid that exhibits biological activities and can reduce lipopolysaccharide (LPS) induced liver injury, but it is unknown if it acts via the gut-liver axis. In the study, a mouse model was established to assess the positive role and mechanisms of sinensetin upon LPS-induced liver injury. The results indicated that sinensetin improved abnormal histopathological changes in the intestine and liver, restored the function of the intestinal barrier, and inhibited LPS induced activation of toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB)/NLR family pyrin domain containing 3 (NLRP3) pathway. Moreover, microbiota composition revealed that sinensetin improved intestinal imbalance by improving the gut microbiota dysbiosis and short chain fatty acid (SCFA) level. Overall, this study revealed that sinensetin alleviated LPS induced liver injury by targeting the TLR4/NF-κB/NLRP3 pathway and related gut-liver axis dysfunction in mice. It provides new ideas for utilizing functional factors in food to improve LPS induced liver injury.