{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T15:19:56Z","timestamp":1783437596958,"version":"3.54.6"},"reference-count":40,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","license":[{"start":{"date-parts":[[2023,1,27]],"date-time":"2023-01-27T00:00:00Z","timestamp":1674777600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/ http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"abstract":"<jats:p>Non-alcoholic steatohepatitis (NASH) has become a major cause of liver transplantation and liver-associated death. The gut-liver axis is a potential therapy for NASH. Sodium cholate (SC) is a choleretic drug whose main component is bile acids and has anti-inflammatory, antifibrotic, and hepatoprotective effects. This study aimed to investigate whether SC exerts anti-NASH effects by the gut-liver axis. Mice were fed with an high-fat and high-cholesterol (HFHC) diet for 20 weeks to induce NASH. Mice were daily intragastric administrated with SC since the 11th week after initiation of HFHC feeding. The toxic effects of SC on normal hepatocytes were determined by CCK8 assay. The lipid accumulation in hepatocytes was virtualized by Oil Red O staining. The mRNA levels of genes were determined by real-time quantitative PCR assay. SC alleviated hepatic injury, abnormal cholesterol synthesis, and hepatic steatosis and improved serum lipid profile in NASH mice. In addition, SC decreased HFHC\u2013induced hepatic inflammatory cell infiltration and collagen deposition. The target protein-protein interaction network was established through Cytoscape software, and NR1H4 [farnesoid x receptor (FXR)] was identified as a potential target gene for SC treatment in NASH mice. SC-activated hepatic FXR and inhibited CYP7A1 expression to reduce the levels of bile acid. In addition, high-dose SC attenuated the abnormal expression of cancer markers in NASH mouse liver. Finally, SC significantly increased the expression of FXR and FGF15 in NASH mouse intestine. Taken together, SC ameliorates steatosis, inflammation, and fibrosis in NASH mice by activating hepatic and intestinal FXR signaling so as to suppress the levels of bile acid in NASH mouse liver and intestine.<\/jats:p>","DOI":"10.1097\/hc9.0000000000000039","type":"journal-article","created":{"date-parts":[[2023,1,28]],"date-time":"2023-01-28T00:38:25Z","timestamp":1674866305000},"page":"e0039-e0039","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":7,"title":["Sodium cholate ameliorates nonalcoholic steatohepatitis by activation of FXR signaling"],"prefix":"10.1097","volume":"7","author":[{"given":"Linyu","family":"Pan","sequence":"first","affiliation":[{"name":"Guangdong Pharmaceutical University, Guangzhou, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ze","family":"Yu","sequence":"additional","affiliation":[{"name":"Guangdong Pharmaceutical University, Guangzhou, Guangdong, 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