Synthesis and evaluation of 2-cyano-3, 12-dioxooleana-1, 9(11)-en-28-oate-13β, 28-olide as a potent anti-inflammatory agent for intervention of LPS-induced acute lung injury  

作　　者：MOU Yi JIAN Yan-Lin CHEN Tong HUANG Zhang-Jian QIAO Yi-Xue PENG Si-Xun ZHANG Da-Yong JI Hui ZHANG Yi-Hua 

机构地区：[1]State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, China Pharmaceutical University, Nanjing 210009, China [2]State Key Laboratory of Natural Medicines, Department of Pharmacology, China Pharmaceutical University, Nanjing 210009, China

出　　处：《Chinese Journal of Natural Medicines》2017年第5期347-354,共8页中国天然药物（英文版）

摘　　要：The present study was designed to synthesize 2-Cyano-3, 12-dioxooleana-1, 9(11)-en-28-oate-13β, 28-olide(1), a lactone derivative of oleanolic acid(OA) and evaluate its anti-inflammatory activity. Compound 1 significantly diminished nitric oxide(NO) production and down-regulated the m RNA expression of iNOS, COX-2, IL-6, IL-1β, and TNF-α in lipopolysaccharide(LPS)-stimulated RAW264.7 cells. Further in vivo studies in murine model of LPS-induced acute lung injury(ALI) showed that 1 possessed more potent protective effects than the well-known anti-inflammatory drug dexamethasone by inhibiting myeloperoxidase(MPO) activity, reducing total cells and neutrophils, and suppressing inflammatory cytokines expression, and thus ameliorating the histopathological conditions of the injured lung tissue. In conclusion, compound 1 could be developed as a promising anti-inflammatory agent for intervention of LPS-induced ALI.The present study was designed to synthesize 2-Cyano-3, 12-dioxooleana-1, 9（11）-en-28-oate-13β, 28-olide （1）, a lactone derivative of oleanolic acid （OA） and evaluate its anti-inflammatory activity. Compound 1 significantly diminished nitric oxide （NO） production and down-regulated the mRNA expression of iNOS, COX-2, IL-6, IL-1β, and TNF-a in lipopolysaccharide （LPS）-stimulated RAW264.7 cells. Further in vivo studies in murine model of LPS-induced acute lung injury （ALI） showed that 1 possessed more potent protective effects than the well-known anti-inflammatory drug dexamethasone by inhibiting myeloperoxidase （MPO） activity, reducing total cells and neutrophils, and suppressing inflammatory cytokines expression, and thus ameliorating the histopathological conditions of the injured lung tissue. In conclusion, compound 1 could be developed as a promising anti-inflammatory agent for intervention of LPS-induced ALL

关 键 词：Oleanolic acid LACTONE ANTI-INFLAMMATION Acute lung injury 

分 类 号：R965[医药卫生—药理学]