Glycyrrhizin protects against particulate matter-induced lung injury via regulation of endoplasmic reticulum stress and NLRP3 inflammasome-mediated pyroptosis through Nrf2/HO-1/NQO1 signaling pathway

Int Immunopharmacol. 2023 Jul:120:110371. doi: 10.1016/j.intimp.2023.110371. Epub 2023 May 26.

Abstract

Particulate matter (PM) is a major environmental pollutant that contributes considerably to deaths worldwide. The pathogenesis of PM-induced lung injury (PILI) is far from elucidated and warrants effective intervention. An effective component of licorice, glycyrrhizin (GL), has been the subject of much research due to its anti-inflammatory and anti-oxidative capabilities. Although preventive properties of GL are well-known, the precise mechanism of GL in PILI has not yet been investigated. A mouse model of PILI was used to examine the protective effects of GL in vivo, and a human bronchial epithelial cells (HBECs) model was used in vitro. In order to determine whether GL mitigates PILI, its effects on endoplasmic reticulum (ER) stress, NLRP3 inflammasome-mediated pyroptosis and the oxidative response were examined. According to the findings, GL reduced PILI and activate anti-oxidative Nrf2/HO-1/NQO1 signaling in mice. Notably, the effect of GL on PM-induced ER stress and NLRP3 inflammasome-mediated pyroptosis was significantly attenuated by the Nrf2 inhibitor ML385. The data suggest that via the anti-oxidative Nrf2 signaling, GL may reduce oxidative stress-mediated ER stress and NLRP3 inflammasome-mediated pyroptosis. Therefore, GL may serve as a promising treatment for PILI.

Keywords: ER stress; Glycyrrhizin; NLRP3; Nrf2; Particulate matter; Pyroptosis.

MeSH terms

  • Animals
  • Endoplasmic Reticulum Stress
  • Glycyrrhizic Acid / pharmacology
  • Glycyrrhizic Acid / therapeutic use
  • Humans
  • Inflammasomes* / metabolism
  • Lung Injury*
  • Mice
  • NAD(P)H Dehydrogenase (Quinone) / metabolism
  • NF-E2-Related Factor 2 / metabolism
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism
  • Particulate Matter / toxicity
  • Pyroptosis
  • Signal Transduction

Substances

  • Inflammasomes
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Glycyrrhizic Acid
  • NF-E2-Related Factor 2
  • Particulate Matter
  • NQO1 protein, human
  • NAD(P)H Dehydrogenase (Quinone)