| Summary: | Liver fibrosis can be caused by non-alcoholic steatohepatitis (NASH), among other conditions. We performed a study to analyze the effects of a nontoxic, water-soluble extract of the edible mushroom <i>Agaricus bisporus</i> (AB) as a potential inhibitor of fibrosis progression in vitro using human hepatic stellate cell (LX2) cultures and in vivo in <i>LDLR-/-</i> mice. Treatment of LX2 cells with the AB extract reduced the levels of fibrotic and oxidative-related markers and increased the levels of GATA4 expression. In <i>LDLR-/-</i> mice with high-fat diet (HFD)-induced liver fibrosis and inflammation, the progression of fibrosis, oxidative stress, inflammation, and apoptosis were prevented by AB extract treatment. Moreover, in the mouse model, AB extract could exert an antiatherogenic effect. These data suggest that AB mushroom extract seems to exert protective effects by alleviating inflammation and oxidative stress during the progression of liver fibrosis, possibly due to a decrease in Toll-like receptor 4 (<i>TLR4</i>) expression and a reduction in Nod-like receptor protein 3 (NLRP3) inflammasome activation. In addition, we observed a potential atheroprotective effect in our mouse model.
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