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

作　　者：Ya-xian Wu Ying-ying Wang Zhi-qi Gao Dan Chen Gang Liu Bin-bin Wan Feng-juan Jiang Ming-xia Wei Jing Zuo Jun Zhu Yong-quan Chen Feng Qian Qing-feng 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》2021年第12期2069-2081,共13页中国药理学报（英文版）

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 

分 类 号：R285.5[医药卫生—中药学]