Fucoxanthin exert dose-dependent antifibrotic and anti-inflammatory effects on CCl₄-induced liver fibrosis

The lack of an effective non-surgical liver fibrosis treatment is a major problem in hepatology. Fucoxanthin is a marine xanthophyll that exhibits anti-inflammatory, antioxidant, and hepatoprotective properties, thereby indicating its potential effectiveness in the treatment of liver fibrosis. The study aims to investigate the antifibrotic and anti-inflammatory effects of fucoxanthin and its main mechanisms on carbon tetrachloride (CCl₄)-induced liver fibrosis in 50 outbred ICR/CD1 mice. 2 μl/g of CCl₄ were injected intraperitoneally 2 times a week for 6 weeks. Fucoxanthin (5, 10, 30 mg/kg) was administered via gavage. Liver histopathology was evaluated by Hematoxylin-Eosin (H&E) and Sirius Red staining using the METAVIR scale. The immunohistochemical method was used to determine the number of CD45 and α-smooth muscle actin (α-SMA) positive cells, and tissue inhibitor of matrix metalloproteinases-1 (TIMP-1), matrix metalloproteinase-9 (MMP-9), and α-SMA positive areas. Using enzyme immunoassays, procollagen 1 (COL1A1), transforming growth factor-β (TGF-β), and hepatocyte growth factor (HGF) were determined in homogenate, and interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) were determined in blood serum. Serum alanine aminotransferase (ALT) and aspartate transaminase (AST) activity, albumin (ALB), and total bilirubin (Tbil) levels are determined by biochemical assays. Fucoxanthin significantly reduced the severity of liver fibrosis, profibrogenic markers, inflammatory infiltration, and pro-inflammatory cytokines. In summary, we confirmed that fucoxanthin has a dose-dependent antifibrotic effect on CCl₄-induced liver fibrosis. We found that the anti-inflammatory effect of fucoxanthin is related to the inhibition of IL-1β and TNF-α synthesis, as well as the decrease in the number of leukocytes in the injured liver.