Schisandrin B Elevates Plasma Glutathione Redox Status and Modulates Hepatokines for Extrahepatic Metabolic Regulation

Schisandrin B (Sch B), a bioactive lignan derived from Schisandrae chinensis Fructus, exhibits well-documented tissue-protective properties, yet its systemic metabolic effects mediated by liver-derived factors remain elusive. This study investigated the capacity of Sch B to modulate systemic redox status and hepatokine secretion in a mouse model. Following oral administration of Sch B, treated animals demonstrated a significantly elevated plasma glutathione (GSH/GSSG) ratio, reflecting a robust enhancement of systemic antioxidant capacity essential for extrahepatic tissue protection. Concurrently, Sch B induced a highly favorable reprogramming of circulating hepatokines by downregulating angiopoietin-like proteins 3 and 4 (ANGPTL3 and ANGPTL4) while upregulating the insulin-sensitizing hormone adropin. Because ANGPTL3/4 act as lipase inhibitors, this coordinated shift theoretically promotes an atheroprotective lipid profile alongside enhanced energy expenditure and glucose homeostasis. Collectively, these findings demonstrate that Sch B exerts beneficial systemic metabolic effects through coupled redox enhancement and hepatokine regulation, underscoring its potential as a therapeutic agent for metabolic disorders.