Anti-inflammtory Activity Screening And Mechanism Research Of Diphenylethene And Phenanthrene Analogues

Inflammation is an adaptive response that is triggered by noxious stimuliand conditions, such as infection and tissue injury. Controlled inflammatory response is beneficial in providing protection against infection and tissue injury, but excessive inflammatory response can lead to auto-immune diseases, diabetes, cardiovascular diseases, even cancer. Natural diphenylethene and phenanthrene derivatives are considered to be important resource for the anti-inflammatory therapeutics, but their structure-activity relationship and mechanisms are still unknown.In this study, we evaluated 20 synthesized phenanthrene analogues in lipopolysaccharide(LPS)-stimulated RAW264.7 macrophages. Compounds 10, 11 and 17 were found to inhibit the production of nitric oxide(NO) with IC50 values of 37.26 ?M, 5.05 ?M and 20.31 ?M, respectively.Meanwhile, compound 11 decreased LPS-induced expression of inducible NO synthase(iNOS), interleukin-1? and interleukin-6 in a concentrantion-dependent manner.In the study of anti-inflammatory mechanism of compound 11, we found it inhibited the phosphorylation of p38 mitogen-activated protein kinase(MAPK) and serine/threonine kinase Akt. It also suppressed the phosphorylation and degradation of inhibitory kappaB-?(I?B?). Data obtained suggest that compound 11 exerts antiinflammatory effects by inhibiting p38 MAPK and nuclear factor ?B(NF-?B) pathways, which warrants further investigation as a new anti-inflammatory pharmaceutical tool.