Acute liver injury (ALI) induced by lipopolysaccharide (LPS) represents a critical clinical challenge due to its high mortality and limited therapeutic options. Fucoxanthin (Fx), a marine-derived xanthophyll carotenoid, exerts hepatoprotective potential owing to its strong anti-inflammatory and antioxidant properties. However, its protective role against LPS-induced ALI remains poorly understood. This study elucidated the protective effect and underlying mechanism of Fx against LPS-induced ALI in both a mouse model and a hepatocyte-macrophage co-culture system. Oral administration of 50 or 200 mg/kg body weight Fx once daily for 7 consecutive days notably attenuated LPS-induced increase in serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, and improved pathological changes in mouse livers. In the co-culture system of AML12 hepatocytes and RAW264.7 macrophages, Fx treatment dose-dependently alleviated LPS-induced damage to AML12 cells, as evidenced by reduced lactate dehydrogenase (LDH) release and maintained cell viability. Mechanistically, Fx significantly suppressed macrophage overactivation-mediated hepatic inflammatory responses and oxidative stress induced by LPS. Specifically, Fx downregulated pro-inflammatory molecules, such as tumor necrosis factor-alpha (TNF- α ), interleukin-1beta (IL-1 β ), IL-6, IL-18, and inducible nitric oxide synthase (iNOS), as well as inhibited intracellular reactive oxygen species (ROS) generation. These effects collectively suppressed excessive hepatocyte apoptosis via blocking the intrinsic apoptotic signaling pathway and inhibited massive hepatocyte pyroptosis through inactivating the NOD-like receptor family pyrin domain containing 3 (NLRP3)/caspase-1/ gasdermin D (GSDMD)-mediated pyroptosis pathway. Collectively, these findings suggest that Fx may serve as a promising functional ingredient for preventing ALI. • Fx exerts a profound protective effect against LPS-induced ALI in both a mouse model and a hepatocyte-macrophage co-culture system. • Fx mitigates macrophage overactivation-mediated hepatic inflammatory responses and oxidative stress induced by LPS. • Fx alleviates LPS-induced excessive hepatocyte apoptosis via inactivation of the intrinsic apoptotic signaling pathway. • Fx attenuates LPS-induced massive hepatocyte pyroptosis through suppression of the NLRP3/caspase-1/GSDMD-mediated pyroptosis pathway.
Yang et al. (Wed,) studied this question.