The objective of this study was to evaluate whether fucoxanthin (FCX) have anti-fibrogenic properties in hepatic stellate cells (HSCs). FCX significantly decreased basal and transforming growth factor beta 1 (TGF beta 1)-induced mRNA levels of fibrogenic genes with concomitant decreases in their protein levels in LX-2 cells. The phosphorylation of SMA- and MAD-related protein (SMAD3) was increased by TGF beta 1, which was attenuated by FCX. Importantly, when LX-2 cells were treated with FCX and SIS3, a SMAD3 inhibitor, there was synergistic repression of fibrogenic gene expression. The anti-fibrogenic effect of FCX was also confirmed in primary human HSCs. FCX prevented TGF beta 1-induced accumulation of reactive oxygen species by diminishing mRNA level of NADPH oxidase 4 (NOX4) in LX-2 cells. When FCX was present during the activation of quiescent mouse primary HSCs, it decreased the expression of fibrogenic genes while diminishing intracellular lipid droplets. The results suggest that FCX exerts an anti-fibrogenic effect in HSCs primarily by preventing TGF beta 1-induced pro-fibrogenic genes expression via inhibition of SMAD3 activation and by inhibiting the activation of quiescent HSCs. (C) 2019 Elsevier Inc. All rights reserved.