Chelerythrine-mediated targeting of NF-κB and Nrf2 pathways alleviates liver injury in a carbon tetrachloride-induced liver fibrosis mouse model.

This study aimed to investigate the mechanism and efficacy of chelerythrine (CHE) in treating carbon tetrachloride (CCl4)-induced liver fibrosis, with a particular focus on the nuclear factor-erythroid-related factor-2 (Nrf2) and nuclear factor-kappa-B (NF-κB) signaling pathways. Mice were induced with CCl4 for eight weeks and categorized into the control group, CCl4 model group, and CHE low (7 mg/kg/d, ig,), medium (14 mg/kg/d, ig), and high-dose (28 mg/kg/d, ig) groups with 10 animals in each group. Following CHE treatment, liver sample morphology was assessed using multiple immunohistochemistry, and serum biochemical indicators were measured. ELISA was used to determine IL-10, IL-1β, and TNF-α contents. Western blotting and RT-PCR were employed to analyze protein and mRNA levels of α-SMA, Col-I, fibronectin, Nrf2, HO-1, NQO1, GCLc, GCLm, NF-κB, p-NF-κB, IκBα, and p-IκBα. Nrf2 knockout mice were used to assess the impact of CHE on the Nrf2 signaling pathway. The findings demonstrated that CHE significantly ameliorated oxidative damage, inflammatory response, and liver fibrosis in CCl4-induced mice. CHE treatment increased Nrf2 expression and its target proteins, including HO-1 and GCLc, an effect not observed in Nrf2 knockout mice. In addition, CHE reduced NF-κB expression levels. These results suggest that CHE can alleviate liver fibrosis in CCl4-induced mice by modulating NF-κB/IκBα and Nrf2 signaling pathways. These findings propose CHE as a potential novel anti-liver fibrosis drug.