a novel compound c12 inhibits inflammatory cytokine production and protects from inflammatory injury in vivo一种新型复合c12抑制炎性细胞因子的生产和保护从体内炎性损伤.pdfVIP

A Novel Compound C12 Inhibits Inflammatory Cytokine Production and Protects from Inflammatory Injury In Vivo 1. 1. 1 1 2 1 2 3 Yi Wang , Congcong Yu , Yong Pan , Jianling Li , Yali Zhang , Faqing Ye , Shulin Yang , Hui Zhang , Xiaokun Li1,4, Guang Liang1,2* 1 Bioorganic and Medicinal Chemistry Research Center, School of Pharmaceutical Science, Wenzhou Medical College, Wenzhou, People’s Republic of China, 2 Institute of Bioengineering, Nanjing University of Science and Technology, Nanjing, People’s Republic of China, 3 Department of Pharmacy, The First Affiliated Hospital, Wenzhou Medical College, Wenzhou, People’s Republic of China, 4 Norman Bethune College of Medical Science, Jilin University, Changchun, People’s Republic of China Abstract Inflammation is a hallmark of many diseases. Although steroids and cyclooxygenase inhibitors are main anti-inflammatory therapeutical agents, they may cause serious side effects. Therefore, developing non-steroid anti-inflammatory agents is urgently needed. A novel hydrosoluble compound, C12 (2,6-bis(4-(3-(dimethylamino)-propoxy)benzylidene)cyclohexanone), has been designed and synthesized as an anti-inflammatory agent in our previous study. In the present study, we investigated whether C12 can affect inflammatory processes in vitro and in vivo. In mouse primary peritoneal macrophages, C12 potently inhibited the production of the proinflammatory gene expression including TNF-a, IL-1b, IL-6, iNOS, COX-2 and PGE synthase. The activity of C12 was partly dependent on inhibition of ERK/JNK (but p38) phosphorylation and NF-kB activation. In vivo, C12 suppressed proinflammatory cytokine production in plasma and