Ethyl ferulate protects against lipopolysaccharide-induced acute lung injury by activating AMPK/Nrf2 signaling pathway

查看全文 作　　者：Ya-xian [1,2]Wu;Ying-ying [1]Wang;Zhi-qi [1]Gao;Dan [1]Chen;Gang [1]Liu;Bin-bin [1]Wan;Feng-juan [1]Jiang;Ming-xia [1]Wei;Jing [1]Zuo;Jun [1]Zhu;Yong-quan [1,2]Chen;Feng [3]Qian;Qing-feng [1]Pang

机构地区：[1]Wuxi School of Medicine,Jiangnan University,Wuxi 214122,China;[2]School of Food Science and Technology,Jiangnan University,Wuxi 214122,China;[3]Engineering Research Center of Cell&Therapeutic Antibody,Ministry of Education,School of Pharmacy,Shanghai Jiao Tong University,Shanghai 200240,China

出　　处：《Acta Pharmacologica Sinica》索引2021年第42卷第12期,共13页

基　　金：supported by the National Natural Science Foundation of China(81871518,81901522);China Postdoctoral Science Foundation(2020M671347);Fundamental Research Funds for the Central Universities(JUSRP11955);Natural Science Foundation of Jiangsu Province(BK20200602);the Wuxi Health and Family Planning Commission(Z201810);the Public Health Research Center at Jiangnan University(JUPH201805). 摘　　要：Ethyl ferulate(EF)is abundant in Rhizoma Chuanxiong and grains(e.g.,rice and maize)and possesses antioxidative,antiapoptotic,antirheumatic,and anti-inflammatory properties.However,its effect on lipopolysaccharide(LPS)-induced acute lung injury(ALI)is still unknown.In the present study,we found that EF significantly alleviated LPS-induced pathological damage and neutrophil infiltration and inhibited the gene expression of proinflammatory cytokines(TNF-α,IL-1β,and IL-6)in murine lung tissues.Moreover,EF reduced the gene expression of TNF-α,IL-1β,IL-6,and iNOS and decreased the production of NO in LPS-stimulated RAW264.7 cells and BMDMs.Mechanistic experiments revealed that EF prominently activated the AMPK/Nrf2 pathway and promoted Nrf2 nuclear translocation.AMPK inhibition(Compound C)and Nrf2 inhibition(ML385)abolished the beneficial effect of EF on the inflammatory response.Furthermore,the protective effect of EF on LPS-induced ALI was not observed in Nrf2 knockout mice.Taken together,the results of our study suggest that EF ameliorates LPS-induced ALI in an AMPK/Nrf2-dependent manner.These findings provide a foundation for developing EF as a new anti-inflammatory agent for LPS-induced ALI/ARDS therapy. 关键词：ethyl ferulate acute lung injury LIPOPOLYSACCHARIDE inflammation AMPK NRF2

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Ethyl ferulate protects against lipopolysaccharide-induced acute lung injury by activating AMPK/Nrf2 signaling pathway

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