Schisandrin B alleviates hepatic damage and hepatic lipid metabolic dysregulation induced by microcystin-LR.

Abstract

Microcystin-LR (MC-LR) is a common biological pollutant found in aquatic environments; it induces severe liver injury, inflammation and lipid metabolic disorders. The potential mechanisms underlying MC-LR pathogenesis is still unclear, and effective therapeutic drugs remain to be explored through in-depth research. This study was designed to systematically evaluate and clarify the protective effects and mechanisms of Schisandrin B (SchB) against MC-LR-induced hepatotoxicity. The animal study indicated that SchB alleviated MC-LR-triggered body weight loss, hepatomegaly, liver dysfunction, inflammatory responses and histopathological damage (all p＜0.05). Biochemical analysis and qRT-PCR results demonstrated that SchB ameliorated triglyceride and total cholesterol levels by regulating lipogenic and lipolytic gene expression (all p＜0.05). Bioinformatics and molecular docking identified IL-6 as a potential binding target of SchB, with IL-6 was induced by MC-LR. Further, GO and KEGG bioinformatic analysis combined with Western blot demonstrated that SchB attenuated MC-LR-induced excessive AKT-FOXO1 cascade activation (all p＜0.05), and SC79, a selective AKT activator, partially reversed the hepatoprotective effects of SchB, as evidenced by altered serum ALT/AST levels, hepatic inflammatory cytokines (TNF-α, IL-6), lipid metabolism-related genes (SREBP1c、SCD1、ACC1、PPARα), and antioxidant indicators (SOD and CAT), a finding further supported by in vivo animal studies (all p＜0.05). These results indicate that SchB attenuates MC-LR-induced hepatic toxicity and suppresses excessive AKT/FOXO1 activation, suggesting SchB as a promising hepatoprotective candidate against MC-LR exposure.