White button mushroom extracts modulate hepatic fibrosis progression, inflammation, and oxidative stress in vitro and in ldlr-/-mice

Abstract

Liver fibrosis can be caused by non-alcoholic steatohepatitis (NASH), among other condi-tions. We performed a study to analyze the effects of a nontoxic, water-soluble extract of the edible mushroom Agaricus bisporus (AB) as a potential inhibitor of fibrosis progression in vitro using human hepatic stellate cell (LX2) cultures and in vivo in LDLR-/-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 LDLR-/-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 (TLR4) 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.This research was funded by the Junta de Andalucía (PAI-BIO311) and Ministerio de Economía y Competitividad (AGL2017-86927-R) to F.M. A.L.-S. was supported by Junta de Andalucía (PAI-BIO311); Instituto de Salud Carlos III (PI14/01349) integrated in the national I+D+i 2013-2016 and co-funded by European Union (ERDF/ESF, “Investing in your future”). J.A.D.C. is supported by Nicolás Monardes Program from Servicio Andaluz de Salud (SAS)