Brevicompanine E reduces lipopolysaccharide-induced production of proinflammatory cytokines and enzymes in microglia by inhibiting activation of activator protein-1 and nuclear factor-κB

【作者】 杨新颖；

【Author】 Xinying Yang

【机构】 中国科学院上海生命科学研究院营养研究所；

【摘要】 <正>Excessive release of proinflammatory cytokines by activated microglia can cause neurotoxicity in neurodegenerative diseases.We found that Brevicompanine E(BE),isolated from a deep ocean sediment derived fungus Penicillium sp.,inhibited lipopolysaccharide(LPS)-induced tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),inducible nitric oxide(iNOS) and cyclooxygenase-2(COX-2) production in microglia.Moreover,electrophoretic mobility shift assay(EMSA) demonstrated that BE attenuated nuclear factor-κB(NF-κB) and activator protein-1 (AP-1) DNA binding activity in LPS-induced microglia.Consistent with this finding,BE inhibited LPS-induced IκBαdegradation,NF-κB nuclear translocation,and also Akt,c-Jun NH2-terminal kinase(JNK) phosphorylation.Thus,BE may be potentially useful for modulating neuroinflammation.更多还原

【Abstract】 Excessive release of proinflammatory cytokines by activated microglia can cause neurotoxicity in neurodegenerative diseases.We found that Brevicompanine E(BE),isolated from a deep ocean sediment derived fungus Penicillium sp.,inhibited lipopolysaccharide(LPS)-induced tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),inducible nitric oxide(iNOS) and cyclooxygenase-2(COX-2) production in microglia.Moreover,electrophoretic mobility shift assay(EMSA) demonstrated that BE attenuated nuclear factor-κB(NF-κB) and activator protein-1 (AP-1) DNA binding activity in LPS-induced microglia.Consistent with this finding,BE inhibited LPS-induced IκBαdegradation,NF-κB nuclear translocation,and also Akt,c-Jun NH2-terminal kinase(JNK) phosphorylation.Thus,BE may be potentially useful for modulating neuroinflammation.更多还原