Pharmacodyamic study and potential mechanism of Qingjin Yiqi Decoction for the treatment of COVID-19
[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 1 β(IL-1 β),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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