Nomilin and its analogue obacunone alleviate NASH and hepatic fibrosis in mice via enhancing antioxidant and anti ‐inflammation capacity

Nomilin and obacunone exert beneficial effects on MCD-, BDL-, and CCl4-induced NASH mice. Nomilin and obacunone alleviate NASH and liver fibrosis via enhancing antioxidant and anti-inflammation capacity. AbstractNonalcoholic steatohepatitis (NASH) and hepatic fibrosis are leading causes of cirrhosis with rising morbidity and mortality worldwide. 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-deficient (MCD) diet, carbon tetrachloride (CCl4)-treated and bile duct ligation (BDL) NASH and hepatic fibrosis mouse models. Mechanistic studies showed that NML and OBA enhanced anti-oxidative effects, including reduction of malondialdehyde (MDA) level, increase of catalase (CAT) activity and the gene expression ofglutathione S-transferases (GSTs) and Nrf2-keap1 signaling. Additional, NML and OBA inhibited the expression of inflammatory geneinterleukin 6 (Il-6), and regulated the bile acid metabolism genesCyp3a11,Cyp7a1,multidrug resistance-associated protein 3 (Mrp3). Overall, these findings indicate that NML and OBA may a...
Source: BioFactors - Category: Biochemistry Authors: Tags: RESEARCH ARTICLE Source Type: research