Dihydroquercetin ameliorates alcoholic liver steatosis through P2x7R-NLRP3 inflammasome pathway  

作　　者：Yu ZHANG Xia LI Kai-li XIA Min JIANG Ben-wen CUI Yan-ling WU Ji-xing NAN Li-hua LIAN 

机构地区：[1]Key Laboratory for Natural Resource of Changbai Mountain & Functional Molecules, Ministry of Education, College of Pharmacy, Yanbian University, Yanji 133002, China

出　　处：《中国药理学与毒理学杂志》2018年第4期338-339,共2页Chinese Journal of Pharmacology and Toxicology

基　　金：supported by National Natural Science Foundation of China(81560597;81260664;81360658;and 81660689)

摘　　要：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.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.

关 键 词：二氢黄酮 酒精肝 治疗方法 化合物 

分 类 号：R284.1[医药卫生—中药学] R575[医药卫生—中医学]