1. Academic Validation
  2. Limonin, a novel AMPK activator, protects against LPS-induced acute lung injury

Limonin, a novel AMPK activator, protects against LPS-induced acute lung injury

  • Int Immunopharmacol. 2023 Jul 21;122:110678. doi: 10.1016/j.intimp.2023.110678.
Hui Liang 1 Gaoli Liu 2 Qinglu Fan 2 Zhihao Nie 2 Songping Xie 2 Renquan Zhang 3
Affiliations

Affiliations

  • 1 Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China.
  • 2 Department of Thoracic Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, China.
  • 3 Department of Thoracic Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China. Electronic address: zhangrenquan@live.cn.
Abstract

AMP-activated protein kinase (AMPK) activation plays crucial roles in the treatment of many oxidative stress- and inflammation-induced diseases, including acute lung injury (ALI). Limonin is a naturally occurring tetracyclic triterpenoid extracted from the Plants of Rutaceae and Meliaceae. Limonin also serves as an AMPK Activator with anti-inflammatory and anti-oxidation effects. However, the potential beneficial effects of limonin on ALI and the possible mechanisms have never been disclosed till now. Here, the effects of limonin on lipopolysaccharide (LPS)-induced ALI in C57 BL/6 mice, plus bone marrow-derived macrophages (BMDM) stimulated with LPS to induce in vitro ALI model were investigated. Limonin significantly improved pulmonary function and alleviated lung pathological injury in LPS-induced mice. Meanwhile, limonin also markedly decreased inflammation and oxidative stress in lung tissues from LPS-treated mice. In vitro experiments also unveiled that limonin could decrease inflammation and oxidative stress in LPS-induced BMDM in a concentration-dependent manner. Mechanically, limonin could promote the activation of AMPKα and upregulate the expression of nuclear factor erythroid 2-related factor 2 (NRF2) in lung tissues and BMDM. Pharmacological inhibition of AMPKα by Compound C or AMPKα knockout could abolish the pulmonary protection from limonin during ALI. In conclusion, limonin mediates the activation of AMPKα/NRF2 pathway, providing an attractive therapeutic target for ALI in the future.

Keywords

AMPKα; Acute lung injury; Limonin; Macrophage; NRF2.

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