Fucoxanthin Ameliorates Carbon Tetrachloride-Induced Liver Fibrosis in Mice via Nrf2/HO-1/GPX4-Mediated Ferroptosis Pathway.

Liver fibrosis, closely linked to oxidative stress, remains a significant global health challenge. Fucoxanthin (Fx), a marine carotenoid extracted from brown algae, exhibits potent antioxidant properties, yet its molecular mechanism in liver fibrosis remains unclear. In the present study, a murine model of liver fibrosis was established through intraperitoneal injection of carbon tetrachloride (CCl4) to investigate the therapeutic potential and underlying mechanisms of Fx. Histological staining and transmission electron microscopy were utilized to evaluate liver morphology, while assessments were conducted on hepatic function indicators, antioxidant indices, liver fibrosis markers, and inflammatory factors. Notably, treatment with Fx resulted in a significant improvement in serum liver function indicators compared to CCl4 model mice. Furthermore, the levels of liver fibrosis markers and inflammatory factors were significantly decreased following Fx treatment. Moreover, Fx treatment led to a significant downregulation of hydroxyproline and alpha-smooth muscle actin (α-SMA) expression, while upregulating key antioxidative and ferroptosis-related proteins. These proteins include nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), NAD(P)H:quinone oxidoreductase 1 (NQO1), glutamate-cysteine ligase modifier (GCLM), glutathione peroxidase 4 (GPX4), solute carrier family 7 member 11 (SLC7A11), transferrin receptor 1 (TFR1), and ferritin light chain (FTL) protein expression, in comparison to the CCl4 model mice. These findings suggest that Fx could effectively ameliorate liver fibrosis by mitigating CCl4-induced oxidative stress and ferroptosis, highlighting its therapeutic potential in liver fibrosis management.