Qinlian Hongqu\nDecoction Modulates FXR/TGR5/GLP‑1\nPathway to Improve Insulin Resistance in NAFLD Mice: Bioinformatics\nand Experimental Study

<b>Background:</b> Qinglian Hongqu decoction (QLHQD),\na traditional\nChinese herbal remedy, shows potential in alleviating metabolic issues\nrelated to nonalcoholic fatty liver disease (NAFLD). However, its\nprecise mode of action remains uncertain. <b>Objective:</b> This\nstudy aims to evaluate the efficacy and mechanisms of QLHQD in treating\nNAFLD. <b>Methods:</b> This study utilized a NAFLD mouse model\nto assess the effects of QLHQD on lipid metabolism, including blood\nlipids and hepatic steatosis, as well as glucose metabolism, including\nblood glucose levels, OGTT results, and serum insulin. Network pharmacology,\nbioinformatics, and molecular docking were used to explore how QLHQD\nmay improve NAFLD treatment. Key proteins involved in these mechanisms\nwere validated via WB and immunohistochemistry. Additionally, the\nexpression of downstream pathway targets was examined to further validate\nthe insulin resistance mechanism by which QLHQD improves NAFLD. <b>Results:</b> Animal studies demonstrated that QLHQD alleviated\nlipid abnormalities, hepatic steatosis, blood glucose levels, the\ninsulin resistance index, and the OGTT results in NAFLD mice (<i>P</i> < 0.05 or 0.01). Network pharmacology and bioinformatics\nanalyses indicated that the effects of QLHQD on NAFLD might involve\nbile acid secretion pathways. Subsequent validation through Western\nblotting, immunohistochemistry, and qPCR demonstrated that QLHQD may\ninfluence fat metabolism and insulin sensitivity in NAFLD mice via\nthe FXR/TGR5/GLP-1 signaling pathway. <b>Conclusion:</b> QLHQD\nsignificantly alleviates glucose and lipid metabolism disorders in\na high-fat diet-induced NAFLD mouse model. Its mechanism of action\nmay involve the activation of the FXR/TGR5/GLP-1 signaling pathway\nin the gut, which reduces lipid accumulation and insulin resistance.