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Moreover, the protective effect of obeticholic acid (OCA) was explored under this condition. <jats:italic>In vivo<\/jats:italic>, female C57BL\/6 mice were administrated with OCA (40\u2009mg\/kg bw, intragastrical injection) before (500\u2009\u03bcg\/kg bw, intragastrical injection)\/LPS (0.1\u2009mg\/kg bw, intraperitoneal injection) administration. <jats:italic>In vitro<\/jats:italic>, AML12 cells were treated with TP (50\u2009nM) and TNF\u2010\u03b1 (50\u2009ng\/ml) to induce hepatotoxicity; GW4064 (5\u2009\u03bcM) and cholestyramine (CHO) (0.1\u2009mg\/ml and 0.05\u2009mg\/ml) were introduced to explain the role of FXR\/total bile acid (TBA) in it. Serum TBA level was significantly elevated, which was induced by FXR suppression. And both GW4064 and CHO intervention presented remarkable protective effects against TP\/TNF\u2010\u03b1\u2010induced NLRP3 upregulation and pyroptosis pathway activation. Pre\u2010administration of FXR agonist OCA successfully attenuated TP\/LPS\u2010induced severe liver injury by reducing serum bile acids accumulation and inhibiting the activation of caspase\u201011\u2010GSDMD (gasdermin D) pyroptosis pathway. We have drawn conclusions that TP aggravated liver hypersensitivity to LPS and inhibited FXR\u2010SHP (small heterodimer partner) axis, which was served as endogenous signals to activate caspase\u201011\u2010GSDMD\u2010mediated pyroptosis contributing to liver injury. OCA alleviated TP\/LPS\u2010induced liver injury accompanied by inhibiting caspase\u201011\u2010GSDMD\u2010mediated pyroptosis pathway and decreased serum TBA level. The results indicated that FXR might be an attractive therapeutic target for TP\/LPS\u2010induced hepatotoxicity, providing an effective strategy for drug\u2010induced liver injury.<\/jats:p>","DOI":"10.1002\/jat.4410","type":"journal-article","created":{"date-parts":[[2022,11,3]],"date-time":"2022-11-03T23:41:23Z","timestamp":1667518883000},"page":"599-614","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Obeticholic acid improved triptolide\/lipopolysaccharide\u2010induced hepatotoxicity by inhibiting caspase\u201011\u2010GSDMD pyroptosis pathway"],"prefix":"10.1002","volume":"43","author":[{"given":"Peishi","family":"Liang","sequence":"first","affiliation":[{"name":"New Drug Screening Center, Jiangsu Center for Pharmacodynamics Research and Evaluation China Pharmaceutical University  Nanjing China"},{"name":"Center for Drug Research and Development Guangdong Pharmaceutical University  Guangzhou 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