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 beta 1 (TGF beta 1)-induced pro-fibrogenic gene expression and oxidative stress in LX-2 cells, a human HSC cell line. TGF beta 1 increased mRNA expression of pro-fibrogenic genes, such as a smooth muscle actin, procollagen type I a1 (COL1A1), COL3A1, and COL6A1, which FCN and ACXA significantly suppressed. Also, an increase in the protein level of COL1A1 by TGF beta 1 was markedly decreased by ACXA. Furthermore, FCN and ACXA significantly inhibited TGF beta 1-induced reactive oxygen species (ROS) accumulation with concomitantly decreasing antioxidant gene expression. Mechanistically, FCN and ACXA markedly increased TGF beta 1-induced nuclear translocation of nuclear E2-related factor 2 (NRF2); however, they significantly attenuated TGF beta 1-induced NFE2L2 and its target gene heme oxygenase-1 expression. The results suggest that FCN and ACXA exert anti-fibrogenic and antioxidant properties by inhibiting TGF beta 1-induced pro-fibrogenic gene expression and ROS accumulation in LX-2 cells.