AUTHOR=Li Wei , Ding Zihe , Chen Ying , Wang Yi , Peng Mingming , Li Chuanqiu , Zhang Han , Zhong Renxing , Xia Tianyi , Zhong Luyang , Zhao Mantong , Yang Mengru , Yue Yimin , Liang Lanyuan , Cao Xia , Shu Zunpeng TITLE=Integrated Pharmacology Reveals the Molecular Mechanism of Gegen Qinlian Decoction Against Lipopolysaccharide-induced Acute Lung Injury JOURNAL=Frontiers in Pharmacology VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.854544 DOI=10.3389/fphar.2022.854544 ISSN=1663-9812 ABSTRACT=

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-α, IL-1β, 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-β 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.