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Pharmacodyamic study and potential mechanism of Qingjin Yiqi Decoction for the treatment of COVID-19
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DOI   10.11656/j.issn.1672-1519.2024.10.15
Key Words   Qingjin Yiqi Decoction;COVID-19;antiviral;anti-inflammatory;network pharmacology;mechanism
Author NameAffiliationE-mail
QIU Wanli Medical College, Henan University, Kaifeng 475001, China  
CHEN Ruihan State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 511436, China  
ZHAO Tingting Eighth School of Clinical Medicine, Guangzhou University of Traditional Chinese Medicine, Foshan 528051, China  
SU Yongjie State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 511436, China  
LI Xuanxuan State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 511436, China  
MA Qinhai State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 511436, China 13268268214@163.com 
YANG Zifeng State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 511436, China jeffyah@163.com 
Abstract
    [Objective] To explore the potential mechanism of action of Qingjin Yiqi Decoction against Coronavirus Disease 2019(COVID-19) through in vitro efficacy study and combined network pharmacology. [Methods] Firstly,Qingjin Yiqi Decoction was used to intervene in the infection of Vero E6 cells with different subtypes of Severe Acute Respiratory Syndrome Coronavirus 2(SARS-CoV-2) virus strains Omicron BA.1,Omicron BA.5 and Omicron XBB,and the antiviral effects of Qingjin Yiqi Decoction were verified by the cytopathic effect(CPE) assay and the plaque reduction assay;then,a model of host inflammatory disorder induced by Sars-CoV-2 virus of Calu3 cells was constructed,and the mRNA expression levels of interleukin 6(IL-6),tumor necrosis factor-α(TNF-α),interferon inducible protein-10(IP-10),and Monocyte chemotactic protein(MCP-1) were detected by Real-Time Quantitative PCR(RT-qPCR) to validate the anti-SARS-CoV-2-induced inflammatory effect of Qingjin Yiqi Decoction. Finally,TCMSP,GeneCards,DrugBank,and other databases were used for network pharmacological analysis. [Results] Qingjin Yiqi Decoction inhibited SARS-CoV-2 strains Omicron BA.1,Omicron BA.5 and Omicron XBB replication in Vero E6 cells,meanwhile,the treatment with Qingjin Yiqi Decoction following infection also had a dose-dependent inhibitory effect on plaque formation of the SARS-CoV-2 virus. Qingjin Yiqi Decoction markedly reduced pro-inflammatory cytokines(IL-6,TNF-α,MCP-1 and IP-10) production at the mRNA levels. By network pharmacological analysis,quercetin,kaempferol,naringenin,beta-sitosterol,and wogonin are the core components of Qingjin Yiqi Decoction;IL-6,TNF,protein kinase B(AKT1),signal transducer and activator of transcription 3(STAT3),interleukin 1β(IL-1β),and tumor protein 53(TP53) were the key targets for the treatment of COVID-19,and the KEGG-enriched pathway mainly involves interleukin 17(IL-17),TNF,phosphatidylinositol-3-kinase-protein kinase B(PI3K-Akt),mitogen-activated protein kinase(MAPK) and other signaling pathways. [Conclusion] Qingjin Yiqi Decoction has broad-spectrum anti-SARS-CoV-2 variant and anti-inflammatory effects. The potential mechanism of action may be through the binding of flavonoid components such as quercetin,kaempferol,wogonin and naringenin to core targets such as IL-6,TNF,AKT1 and STAT3,modulating the virus- and inflammation-associated TNF,the PI3K-Akt and the MAPK signaling pathways,exerting a role in the prevention and treatment of COVID-19. These findings suggest that Qingjin Yiqi Decoction prevents viral attack,making it a novel strategy for controlling COVID-19 disease.

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