Jinyinqingre Oral Liquid alleviates LPS-induced acute lung injury by inhibiting the NF-κB/NLRP3/GSDMD pathway

Chin J Nat Med. 2023 Jun;21(6):423-435. doi: 10.1016/S1875-5364(23)60397-8.

Abstract

Acute lung injury (ALI) is a prevalent and severe clinical condition characterized by inflammatory damage to the lung endothelial and epithelial barriers, resulting in high incidence and mortality rates. Currently, there is a lack of safe and effective drugs for the treatment of ALI. In a previous clinical study, we observed that Jinyinqingre oral liquid (JYQR), a Traditional Chinese Medicine formulation prepared by the Taihe Hospital, Affiliated Hospital of Hubei University of Medicine, exhibited notable efficacy in treating inflammation-related hepatitis and cholecystitis in clinical settings. However, the potential role of JYQR in ALI/acute respiratory distress syndrome (ARDS) and its anti-inflammatory mechanism remains unexplored. Thus, the present study aimed to investigate the therapeutic effects and underlying molecular mechanisms of JYQR in ALI using a mouse model of lipopolysaccharide (LPS)-induced ALI and an in vitro RAW264.7 cell model. JYQR yielded substantial improvements in LPS-induced histological alterations in lung tissues. Additionally, JYQR administration led to a noteworthy reduction in total protein levels within the BALF, a decrease in MPAP, and attenuation of pleural thickness. These findings collectively highlight the remarkable efficacy of JYQR in mitigating the deleterious effects of LPS-induced ALI. Mechanistic investigations revealed that JYQR pretreatment significantly inhibited NF-κB activation and downregulated the expressions of the downstream proteins, namely NLRP3 and GSDMD, as well as proinflammatory cytokine levels in mice and RAW2647 cells. Consequently, JYQR alleviated LPS-induced ALI by inhibiting the NF-κB/NLRP3/GSDMD pathway. JYQR exerts a protective effect against LPS-induced ALI in mice, and its mechanism of action involves the downregulation of the NF-κB/NLRP3/GSDMD inflammatory pathway.

Keywords: Acute lung injury; Inflammation; Jinyinqingre oral liquid; Lipopolysaccharide; NF-κB/NLRP3/GSDMD pathway.

MeSH terms

  • Acute Lung Injury* / chemically induced
  • Acute Lung Injury* / drug therapy
  • Acute Lung Injury* / metabolism
  • Humans
  • Lipopolysaccharides / metabolism
  • Lipopolysaccharides / toxicity
  • Lung
  • NF-kappa B* / metabolism
  • NLR Family, Pyrin Domain-Containing 3 Protein / genetics
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism
  • Phosphate-Binding Proteins / metabolism
  • Phosphate-Binding Proteins / pharmacology
  • Phosphate-Binding Proteins / therapeutic use
  • Pore Forming Cytotoxic Proteins / metabolism
  • Pore Forming Cytotoxic Proteins / pharmacology
  • Pore Forming Cytotoxic Proteins / therapeutic use

Substances

  • NF-kappa B
  • Lipopolysaccharides
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • GSDMD protein, human
  • Phosphate-Binding Proteins
  • Pore Forming Cytotoxic Proteins