Anti-inflammatory effects of novel curcumin analogs in experimental acute lung injury

• DOI: 10.1186/s12931-015-0199-1
• Publication Date: 2015-03-23T13:10:19Z
• Authors: Yali Zhang; Dandan Liang; Lili Dong; Xiangting Ge; Fengli Xu; Wenbo Chen; Yuanrong Dai; Huameng Li; Peng Zou; Shulin Yang; Guang Liang
• Keywords: Proinflammatory cytokine

Acute lung injury (ALI) and its most severe form acute respiratory distress syndrome (ARDS) have been the leading cause of morbidity mortality in intensive care units (ICU). Currently, there is no effective pharmacological treatment for injury. Curcumin, extracted from turmeric, exhibits broad anti-inflammatory properties through down-regulating inflammatory cytokines. However, instability curcumin limits clinical application.A series new analogs were synthesized screened their inhibitory effects on production TNF-α IL-6 mouse peritoneal macrophages by ELISA. The evaluation stability mechanism active compounds was determined using UV-assay Western Blot, respectively. In vivo, SD rats pretreatment with c26 seven days then intratracheally injected LPS to induce ALI. Pulmonary edema, protein concentration BALF, tissue, cytokines serum cell infiltration, mRNA expression, MAPKs phosphorylation analyzed. We also measured gene expression human pulmonary epithelial cells.In study, we 30 analogs. bioscreeening assay showed that inhibited LPS-induced IL-6. compounds, a17, a18, c9 c26, exhibited activity a dose-dependent manner greater than vitro. Furthermore, compound dose-dependently ERK phosphorylation. significantly increased number cells pathological changes macrophage . attenuated induced increase pathway vivo. Meanwhile, reduced cells.These results suggest novel analog has remarkable protective ALI rat. These may be related ability suppress pathway. Compound improved chemical bioactivity, potential further developed into an candidate prevention