Glycyrrhizic Acid Alleviates Lipopolysaccharide (LPS)-Induced Acute Lung Injury by Regulating Angiotensin-Converting Enzyme-2 (ACE2) and Caveolin-1 Signaling Pathway

Inflammation. 2022 Feb;45(1):253-266. doi: 10.1007/s10753-021-01542-8. Epub 2021 Aug 24.

Abstract

Acute lung injury (ALI) is mainly caused by severe infection, shock, trauma, and burn, which causes the extensive release of inflammatory factors and other mediators. As a major bioactive constituent of traditional Chinese herb licorice, glycyrrhizic acid (GA) plays an important effect on inflammatory regulation. Nevertheless, the exact mechanism of this effect remains unclear. The present study aims to explore the potential protective effect of GA on LPS-induced ALI. Our results showed that GA significantly attenuated LPS-induced ALI and decreased the production of inflammatory factors, including IL-1β, MCP-1, COX2, HMGB1, and adhesion molecules, such as E-selectin, VCAM-1, and modulated expression of angiotensin-converting enzyme 2 (ACE2). Moreover, treatment of ACE2 inhibitor (MLN-4760) reversed the effects of GA on the secretion of pro-inflammatory factors in ALI. Additionally, GA exerts its protective effect by regulating the ACE2 and caveolin-1/NF-κB signaling pathway. In conclusion, this study showed that GA alleviated LPS-induced ALI by upregulating ACE2 and inhibiting the caveolin-1/NF-κB signaling pathway.

Keywords: Acute lung injury (ALI); Caveolin-1; NF-κB; angiotensin converting enzyme 2 (ACE2); glycyrrhizic acid (GA).

MeSH terms

  • Acute Lung Injury / drug therapy*
  • Acute Lung Injury / etiology
  • Acute Lung Injury / metabolism
  • Angiotensin-Converting Enzyme 2 / metabolism*
  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Anti-Inflammatory Agents / therapeutic use
  • Biomarkers / metabolism
  • Caveolin 1 / metabolism*
  • Glycyrrhizic Acid / pharmacology*
  • Glycyrrhizic Acid / therapeutic use
  • Human Umbilical Vein Endothelial Cells / drug effects
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Humans
  • Lipopolysaccharides
  • Lung / drug effects*
  • Lung / metabolism
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Signal Transduction / drug effects
  • Treatment Outcome

Substances

  • Anti-Inflammatory Agents
  • Biomarkers
  • Caveolin 1
  • Lipopolysaccharides
  • Glycyrrhizic Acid
  • ACE2 protein, human
  • Ace2 protein, mouse
  • Angiotensin-Converting Enzyme 2