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
• 来源期刊: 中国药理学报（英文版）
• 年，卷（期）: 2021,（12）
• 所属期刊栏目: Pulmonary Pharmacology
• 页码范围: 2069-2081
• 页数: 13页
• 语种: 英文

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 ALl was not observed in Nrf2 knockout mice.Taken together,the results of our study suggest that EF ameliorates LPS-induced ALl 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.