1. Academic Validation
  2. Ethyl ferulate protects against lipopolysaccharide-induced acute lung injury by activating AMPK/Nrf2 signaling pathway

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

  • Acta Pharmacol Sin. 2021 Dec;42(12):2069-2081. doi: 10.1038/s41401-021-00742-0.
Ya-Xian Wu 1 2 Ying-Ying Wang 1 Zhi-Qi Gao 1 Dan Chen 1 Gang Liu 1 Bin-Bin Wan 1 Feng-Juan Jiang 1 Ming-Xia Wei 1 Jing Zuo 1 Jun Zhu 1 Yong-Quan Chen 1 2 Feng Qian 3 Qing-Feng Pang 4
Affiliations

Affiliations

  • 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. fengqian@sjtu.edu.cn.
  • 4 Wuxi School of Medicine, Jiangnan University, Wuxi, 214122, China. qfpang@jiangnan.edu.cn.
Abstract

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.

Keywords

AMPK; Nrf2; acute lung injury; ethyl ferulate; inflammation; lipopolysaccharide.

Figures
Products