Schisandrin B alleviates sulfolane-induced liver injury via the APOA1/ROS/NF-κB signaling pathway.

Sulfolane is a widely used industrial solvent and emerging groundwater contaminant. Sulfolane has hepatotoxicity, but the molecular mechanisms remain poorly understood. Schisandrin B (Sch B), a bioactive lignan isolated from Schisandra chinensis, has been shown to exert hepatoprotective effects. To elucidate the mechanisms underlying sulfolane-induced liver injury and to determine whether Sch B protects against this toxicity by modulating the APOA1/ROS/NF-κB signaling axis. Male C57BL/6 J mice were administered sulfolane (0, 10, 30 or 300 mg/kg) by oral gavage for 28 d, with or without Sch B (8 mg/kg). Liver injury was assessed using histopathology, serum biochemistry, hepatic lipid deposition, ROS levels, and inflammatory marker expression. Bioinformatic analyses integrating "sulfur compound" and "liver injury" datasets were used to identify candidate pathways. The protective effects of Sch B were investigated through APOA1 gene knockdown, APOA1 overexpression, treatment with the antioxidant NAC, and molecular docking experiments of Sch B with APOA1. Sulfolane caused dose-dependent steatosis, oxidative stress and inflammation in mouse liver and AML12 cells. sulfolane suppressed APOA1, increased ROS and activated NF-κB and downstream cytokines. Sch B restored APOA1 expression, reduced ROS accumulation and NF-κB-dependent cytokine production, and markedly improved biochemical and histological indices of liver injury in vivo and in vitro. Sulfolane-induced hepatotoxicity is mediated by suppression of APOA1 and subsequent activation of the NF-κB signaling pathway in a ROS-dependent manner. Schisandrin B protects the liver against this injury by modulating the APOA1/ROS/NF-κB axis.