Licochalcone B confers protective effects against LPS-Induced acute lung injury in cells and mice through the Keap1/Nrf2 pathway

Redox Rep. 2023 Dec;28(1):2243423. doi: 10.1080/13510002.2023.2243423.

Abstract

Background: Acute lung injury (ALI) is a severe and often fatal pulmonary disease. Current treatments for ALI and acute respiratory distress syndrome (ARDS) are limited. Natural product metabolites have shown promise as therapeutic alternatives. However, the effects of Licochalcone B (LCB) on ALI are largely unknown.

Methods: We investigated the effects of LCB on lipopolysaccharide-challenged mice and human pulmonary microvascular endothelial cells. Cell viability, apoptosis, and ROS production were assessed. Lung tissue histopathology and oxidative stress and inflammation markers were evaluated. Protein expression levels were measured.

Results: LCB had no cytotoxic effects on cells and increased cell viability. It reduced apoptosis and ROS levels in cells. In mice with ALI, LCB decreased lung tissue weight and improved oxidative stress and inflammation markers. It also enhanced expression levels of Nrf2, HO-1, and NQO1 while reducing Keap1.

Conclusion: LCB protects against LPS-induced acute lung injury in cells and mice. The Keap1/Nrf2 pathway may be involved in its protective effects. LCB shows potential as a strategy to alleviate ALI caused by LPS.

Keywords: Inflammation; Keap1/Nrf2 pathway; Licochalcone B; Lipopolysaccharide‌; Oxidative stress‌; Therapeutic strategy‌; acute lung injury; oxidative injury.

MeSH terms

  • Acute Lung Injury* / chemically induced
  • Acute Lung Injury* / drug therapy
  • Animals
  • Endothelial Cells / metabolism
  • Humans
  • Inflammation / pathology
  • Kelch-Like ECH-Associated Protein 1 / metabolism
  • Lipopolysaccharides / toxicity
  • Lung / metabolism
  • Mice
  • NF-E2-Related Factor 2 / metabolism
  • Oxidative Stress
  • Reactive Oxygen Species / metabolism

Substances

  • Keap1 protein, mouse
  • Kelch-Like ECH-Associated Protein 1
  • licochalcone B
  • Lipopolysaccharides
  • NF-E2-Related Factor 2
  • Reactive Oxygen Species

Grants and funding

This work was supported by the National Natural Science Foundation of China [grant numbers: 82204778]; the Science and Technology Department of Sichuan Province, China [grant number: 2022YFG0145]; Sichuan Provincial Science and Technology Innovation Seedling Project [grant number: MZGC20230053]; the central government guides local science and technology development projects of Sichuan Provincial Science and Technology Department [grant number: No. 2021ZYD0107].