Neferine Exerts Antioxidant and Anti-Inflammatory Effects on Carbon Tetrachloride-Induced Liver Fibrosis by Inhibiting the MAPK and NF-κB/IκBα Pathways

Reversible liver fibrosis is the consequence of diverse liver injuries. Oxidative stress combined with inflammation is the primary cause of carbon tetrachloride- (CCl(4)-) induced liver fibrosis. Neferine is a bibenzyl isoquinoline alkaloid, which has strong anti-inflammatory and antioxidant properties. The present study attempted to find its antiliver fibrosis effect and explore the potential mechanism to relieve oxidative stress and inflammation in rats with CCl(4)-induced liver fibrosis. Herein, we found that neferine noticeably mitigated fibrosis and improved liver function. Furthermore, neferine increased the activity of antioxidant enzymes, such as superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), and catalase (CAT), but decreased the level of malondialdehyde (MDA). Neferine also decreased the levels of alpha-smooth muscle actin (α-SMA), transforming growth factor β1 (TGF-β1), and inflammatory factors. These results may demonstrate that neferine could effectively inhibit oxidative stress and inflammation in liver fibrosis. To account for the potential mechanism by which neferine relieves oxidative stress and inflammation in liver fibrosis rats, immunohistochemistry analyses and western blotting were performed. The results showed that neferine inhibited the mitogen-activated protein kinase (MAPK) pathway, as evidenced by the reduced phosphorylation of p38 MAPK, ERK 1/2, and JNK. And it inhibited the nuclear factor- (NF-) κB/IκBα pathway, as evidenced by preventing the translocation of NF-κB into nuclei. Our findings indicated a protective role for neferine, acting as an antioxidant and anti-inflammatory agent in CCl(4)-induced liver fibrosis.