Fucoxanthin metabolites exert anti-fibrogenic and antioxidant effects in hepatic stellate cells.

We previously reported an anti-fibrogenic effects of fucoxanthin in hepatic stellate cells (HSCs). However, it is unknown whether the primary metabolites of fucoxanthin, such as fucoxanthinol (FCN) and amarouciaxanthin A (ACXA), exert similar functions in fibrogenesis pathways. In this study, we investigated the role of FCN and ACXA in the regulation of transforming growth factor β1 (TGFβ1)-induced pro-fibrogenic gene expression and oxidative stress in LX-2 cells, a human HSC cell line. TGFβ1 increased mRNA expression of pro-fibrogenic genes, such as α smooth muscle actin, procollagen type I α1 (COL1A1), COL3A1, and COL6A1, which FCN and ACXA significantly suppressed. Also, an increase in the protein level of COL1A1 by TGFβ1 was markedly decreased by ACXA. Furthermore, FCN and ACXA significantly inhibited TGFβ1-induced reactive oxygen species (ROS) accumulation with concomitantly decreasing antioxidant gene expression. Mechanistically, FCN and ACXA markedly increased TGFβ1-induced nuclear translocation of nuclear E2-related factor 2...