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However, no effective treatments are currently available. Thus, there is a critical need to develop novel drugs that can prevent and treat NAFLD with few side effects. In this study, Tussilagone (TUS), a natural sesquiterpene isolated from <jats:italic>Tussilago farfara L<\/jats:italic>, was explored in vitro and in vivo for its potential to treat NAFLD. Our results showed that in vitro TUS reduced oleic acid palmitate acid\u2010induced triglyceride and cholesterol synthesis in HepG<jats:sub>2<\/jats:sub>cells, reduced intracellular lipid droplet accumulation, improved glucose metabolism disorders and increased energy metabolism and reduced oxidative stress levels. In vivo, TUS significantly reduced fat accumulation and improved liver injury in high\u2010fat diet (HFD)\u2010induced mice. TUS treatment significantly increased liver mitochondrial counts and antioxidant levels compared to the HFD group of mice. In addition, TUS was found to reduce the expression of genes involved in lipid synthesis sterol regulatory element binding protein\u20101 (SREBP1), fatty acid synthase (FASN), and stearoy\u2010CoA desaturase 1 (SCD1) in vitro <jats:italic>and<\/jats:italic> in vivo. Our results suggest that TUS may be helpful in the treatment of NAFLD, suggesting that TUS is a promising compound for the treatment of NAFLD. Our findings provided novel insights into the application of TUS in regulating lipid metabolism.<\/jats:p>","DOI":"10.1002\/ptr.7818","type":"journal-article","created":{"date-parts":[[2023,4,3]],"date-time":"2023-04-03T16:07:50Z","timestamp":1680538070000},"page":"2099-2113","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Tussilagone ameliorates high\u2010fat diet\u2010induced hepatic steatosis by enhancing energy metabolism and antioxidant activity"],"prefix":"10.1002","volume":"38","author":[{"given":"Mingjie","family":"Sun","sequence":"first","affiliation":[{"name":"College of Animal Science and Technology Guangxi University  Nanning 530004 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Li","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology Guangxi University  Nanning 530004 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