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Currently, there is no appropriate treatment for NASH and hepatic fibrosis. Many studies have shown that oxidative stress is a main factor inducing NASH. Nomilin (NML) and obacunone (OBA) are limonoid compounds naturally occurring in citrus fruits with various biological properties. However, whether OBA and NML have beneficial effects on NASH remains unclear. Here, we demonstrated that OBA and NML inhibited hepatic tissue necrosis, inflammatory infiltration and liver fibrosis progression in methionine and choline\u2010deficient (MCD) diet, carbon tetrachloride (CCl<jats:sub>4<\/jats:sub>)\u2010treated and bile duct ligation (BDL) NASH and hepatic fibrosis mouse models. Mechanistic studies showed that NML and OBA enhanced anti\u2010oxidative effects, including reduction of malondialdehyde (MDA) level, increase of catalase (CAT) activity and the gene expression of <jats:italic>glutathione S\u2010transferases<\/jats:italic> (<jats:italic>GSTs<\/jats:italic>) and Nrf2\u2010keap1 signaling. Additional, NML and OBA inhibited the expression of inflammatory gene <jats:italic>interleukin 6<\/jats:italic> (<jats:italic>Il\u20106<\/jats:italic>), and regulated the bile acid metabolism genes <jats:italic>Cyp3a11<\/jats:italic>, <jats:italic>Cyp7a1<\/jats:italic>, <jats:italic>multidrug resistance\u2010associated protein 3<\/jats:italic> (<jats:italic>Mrp3<\/jats:italic>). Overall, these findings indicate that NML and OBA may alleviate NASH and liver fibrosis in mice via enhancing antioxidant and anti\u2010inflammation capacity. Our study proposed that NML and OBA may be potential strategies for NASH treatment.<\/jats:p>","DOI":"10.1002\/biof.1987","type":"journal-article","created":{"date-parts":[[2023,7,4]],"date-time":"2023-07-04T13:19:05Z","timestamp":1688476745000},"page":"1189-1204","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Nomilin and its analogue obacunone alleviate NASH and hepatic fibrosis in mice via enhancing antioxidant and anti\u2010inflammation capacity"],"prefix":"10.1002","volume":"49","author":[{"given":"Yongli","family":"Han","sequence":"first","affiliation":[{"name":"School of Pharmacy Shanghai University of Traditional Chinese Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingling","family":"Luo","sequence":"additional","affiliation":[{"name":"School of Pharmacy Shanghai University of Traditional Chinese Medicine  Shanghai 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