4.7 Article

Integrated Pharmacology Reveals the Molecular Mechanism of Gegen Qinlian Decoction Against Lipopolysaccharide-induced Acute Lung Injury

Journal

FRONTIERS IN PHARMACOLOGY
Volume 13, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fphar.2022.854544

Keywords

gegen qinlian decoction; acute lung injury; immunity; intestinal microbiota; multi-omics

Funding

  1. National Natural Science Foundation of China [82174043, 82141211]
  2. Guangdong Basic and Applied Basic Research Foundation [2021A1515011697]
  3. project of Foshan High-tech Zone [2120197000214]
  4. Shunde District, Foshan City [2130218004133]
  5. Characteristic innovation research project of college teachers

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This study found that GQD can improve lung damage and inflammation in LPS-induced ALI rats through multiple pathways, and it can also regulate immune-related pathways and the balance of intestinal microbiota.
ALI is a severe inflammatory disease of the lungs. In previous studies, we found that GQD was effective against ALI, but specific molecular mechanism is still unclear. Therefore, this study was to examine effect of GQD on LPS-induced ALI rats and underlying mechanisms using multi-omics and molecular methods. The results showed that GQD significantly improved lung tissue damage, reduced pulmonary edema, inhibited MPO activity, and improved respiratory function in ALI rat. Additionally, GQD significantly reduced the levels of TNF-alpha, IL-1 beta, and IL-6 in serum and BALF. Furthermore, metabolomic analysis showed that GQD reduced pulmonary inflammation by improving metabolic remodeling. Moreover, transcriptomic analysis showed that GQD inhibited the activation of complement pathway and regulated Th17 and Treg cells balance. Additionally, GQD inhibited the expression of C3, C5a, and IL-17, and promoted the expression of TGF-beta and CYP1A1 at the mRNA and protein levels. Gut microbial assay showed that GQD treatment increased the relative abundance of Firmicutes and their genera in intestinal microbiota, and increased short-chain fatty acids concentration. Overall, GQD treated ALI by improving metabolic remodeling, affecting immune-related pathways and regulating intestinal microbiota. This study provides a solid scientific basis for promoting the clinical use of GQD in treating ALI.

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