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Costunolide (Cos) is a natural sesquiterpene lactone that exhibits both anti\u2010inflammatory and antioxidant properties. However, the therapeutic effect of Cos on NAFLD is not clear. In this study, we explored the potential protective effect and mechanism of Cos on NAFLD. C57BL\/6 mice were fed with high\u2010fat diet (HFD) to induce NAFLD. Cos was administered by gavage to observe the effect of Cos on NAFLD. We demonstrated that oral administration of Cos reduced HFD\u2010induced hepatic fibrosis and the release of inflammatory cytokines, limiting the generation of reactive oxygen species.\u00a0In vitro experiments revealed that pretreatment with Cos significantly decreased PA\u2010induced production of inflammatory cytokines and fibrosis in AML\u201012 cells. Mechanism study showed that the effect of Cos was correlated to the induction of Nrf\u20102 and inhibition of NF\u2010\u03baB pathways. Collectively, these findings indicated that Cos exerts hepatoprotective effect against NAFLD through blocking inflammation and oxidative stress. Our study suggested that Cos might be an effective pharmacotherapy for the treatment of NAFLD.<\/jats:p>","DOI":"10.1002\/ddr.22150","type":"journal-article","created":{"date-parts":[[2024,1,17]],"date-time":"2024-01-17T02:14:18Z","timestamp":1705457658000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Costunolide attenuates high\u2010fat diet\u2010induced inflammation and oxidative stress in non\u2010alcoholic fatty liver disease"],"prefix":"10.1002","volume":"85","author":[{"given":"Jiong","family":"Wang","sequence":"first","affiliation":[{"name":"Joint Research Centre on Medicine The Affiliated Xiangshan Hospital of Wenzhou Medical University Ningbo Zhejiang China"},{"name":"Chemical Biology Research Center, School of Pharmaceutical Sciences Wenzhou Medical University Ningbo Zhejiang 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