文献类型：期刊文献

英文题名：Dual Role of 2',4'-Dihydroxy-6'-methoxy-3',5'-dimethylchalcone in Inhibiting High-Mobility Group Box 1 Secretion and Blocking Its Pro-inflammatory Activity in Hepatic Inflammation

作者：Yu, Wan-Guo[1,2];He, Hao[1,2];Qian, Jie[3];Lu, Yan-Hua[1,2]

机构：[1]E China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[2]Shanghai Collaborat Innovat Ctr Biomfg Technol, Shanghai 200237, Peoples R China;[3]Tongji Univ, Sch Life Sci & Technol, Shanghai 200092, Peoples R China

年份：2014

卷号：62

期号：49

起止页码：11949

外文期刊名：JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY

收录：;EI(收录号：20145100329172);WOS:【SCI-EXPANDED(收录号:WOS:000346321400020)】；

基金：This work was supported by the Fundamental Research Funds for the Central Universities (WF1113010) and partially supported by the National High Technology Research and Development Program of China (2013AA092901) and the National Special Fund for State Key Laboratory of Bioreactor Engineering (2060204).

语种：英文

外文关键词：2',4'-dihydroxy-6'-methoxy-3',5'-dimethylchalcone; hepatic inflammation; high-mobility group box 1; interaction; protein kinase C alpha

摘要：A previous study reported that 2',4'-dihydroxy-6'-methoxy-3',5'-dimethylchalcone (DMC) had a potential hepatoprotective effect through preventing acute liver injury in mice. This study further evaluated the preventive effects of DMC on lipopolysaccharide (LPS)-stimulated hepatic inflammation and the underlying mechanism in liver macrophage. DMC significantly suppressed LPS-stimulated secretion and nucleocytoplasmic translocation of high-mobility group box 1 (HMGB1). DMC could dose-dependently reduce the phosphorylation of phosphatidylinositol 3-kinase (PI3K), protein kinase C alpha (PKCa), and phosphoinositide-dependent kinase 1 (PDK1). Furthermore, HMGB1 phosphorylation, the interaction between PKC and HMGB1, and the expression of HMGB1-dependent inflammation-related molecules were dose-dependently inhibited by DMC. Finally, DMC could target binding to the B box of HMGB1 by molecular modeling studies. All of these results indicated that DMC exhibited a potential protective effect against hepatitis probably via inhibiting HMGB1 secretion and blocking HMGB1 pro-inflammatory activity.