1. Ethyl ferulate protects against lipopolysaccharide-induced acute lung injury by activating AMPK/Nrf2 signaling pathway.
- Author
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Wu YX, Wang YY, Gao ZQ, Chen D, Liu G, Wan BB, Jiang FJ, Wei MX, Zuo J, Zhu J, Chen YQ, Qian F, and Pang QF
- Subjects
- AMP-Activated Protein Kinases metabolism, Acute Lung Injury chemically induced, Acute Lung Injury complications, Acute Lung Injury pathology, Animals, Cytokines metabolism, Gene Knockout Techniques, Inflammation complications, Inflammation drug therapy, Lipopolysaccharides, Lung drug effects, Lung pathology, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Mutation, NF-E2-Related Factor 2 genetics, NF-E2-Related Factor 2 metabolism, Neutrophil Infiltration drug effects, Neutrophils drug effects, Nitric Oxide metabolism, Nitric Oxide Synthase Type II antagonists & inhibitors, RAW 264.7 Cells, Acute Lung Injury drug therapy, Anti-Inflammatory Agents therapeutic use, Caffeic Acids therapeutic use, Signal Transduction drug effects
- 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., (© 2021. The Author(s), under exclusive licence to CPS and SIMM.)
- Published
- 2021
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