Dihydroquercetin ameliorates alcoholic liver steatosis through P2x7R-NLRP3 inflammasome pathway

OBJECTIVE Dihydroquercetin(TAX) is the most abundant dihydroflavone found in on.ions,milk thistle and Douglas fir bark.We investigated whether TAX could inhibit the lipid accumulation in alcoholic liver steatosis in vivo and in vitro.METHODS An in vivo model was established by intragas.trically treating mice with ethanol,and an in vitro model was created by treating HepG2 cells with etha.nol.RESULTS TAX regulated Sterol Regulatory Element-binding Protein-1(SREBP1) and Acetyl CoA Carboxylase(ACC) expression via elevating Liver Kinase B1(LKB1)/AMP-activated Kinase(AMPK)phosphorylation.Also,TAX upregulated SIRT1 expression,which suppressed by ethanal intake.Suppression of Purinergic 2X7 receptor(P2x7R),nucleotide-binding oligomerization domain-like re.ceptor protein 3(NLRP3) and Cysteine protease-1(caspase-1) cleavage by TAX resulted in the inhibi.tion of Interleukin-1β(IL-1β) production and release.Additionally,TAX reduced lipogenesis and pro.moted lipid oxidation via the regulation of AMPK and ACC in ethanol-treated steatotic HepG2 cell.TAX downregulated IL-1β cleavage response to Lipopolysaccharides(LPS) plus adenosine triphosphate(ATP) stimulation in HepG2 cells.P2x7R deficiency attenuated lipid accumulation with increasing AMPK activity and decreasing SREBP1 expression in ethanol-treated HepG2 cells.CONCLUSION Our data showed that TAX exhibited the inhibitory properties on lipogenesis and hepatoprotective ca.pacity,indicating that TAX has therapeutic potential for preventing alcoholic liver steatosis.