Inhibition of P2x7R-NLRP3 inflammasome activation by Pleurotus citrinopileatus: a possible protective role in alcoholic hepatosteatosis.

Pleurotus citrinopileatus (golden oyster mushroom) is a widely used edible mushroom. We investigated the inhibitory effect of P. citrinopileatus aqueous extract against alcoholic steatohepatitis and its underlying mechanism. Acute and chronic ethanol feeding murine models were established by intragastrically administering ethanol or feeding ethanol-containing Lieber-DeCarli liquid diet to male C57BL/6 mice. In both models, P. citrinopileatus decreased serum alanine aminotransferase (ALT), aspartate transaminase (AST), triglyceride (TG) and hepatic TG levels. Hematoxylin and eosin (HE) and Oil red O staining confirmed that P. citrinopileatus ameliorated both of acute and chronic alcoholic hepatosteatosis, characterized by regulation of lipid metabolism-related protein, including sirtuin 1 (SIRT1), AMP-activated kinase (AMPK) and sterol regulatory element-binding protein (SREBP1). P. citrinopileatus reversed inflammatory response via modulating purinergic receptor P2X ligand-gated ion channel 7 (P2x7R)-NOD-like receptor pyrin domains 3 (NLRP3) inflammasome. P. citrinopileatus restored the expression of those protein to normal level. In addition, HepG2 cells were incubated with P. citrinopileatus prior to ethanol stimulation. P. citrinopileatus reduced ethanol exposure-induced lipid deposition. Concomitantly P. citrinopileatus increased AMPK and SIRT1 expression, which were reduced by ethanol treatment. P. citrinopileatus ameliorated alcoholic hepatic steatosis and accompanied inflammatory response via regulating SIRT1-AMPK and P2x7R-NLRP3 inflammasome activation, highlighting a promising strategy and utility of P. citrinopileatus for alcoholic steatohepatitis as dietary health supplements.