《Table 1Summary of the pathogenesis of COVID-19 and therapeutic mechanisms of CHM.》

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《中药治疗新冠病毒肺炎的科学基础》

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Accumulating evidence reveals that a cytokine storm occurs in severe COVID-19 patients，in which the cytokine levels of IL-1B，IL-1RA，IL-6，IL-7，IL-8，IL-9，IL-10，fibroblast growth factor（FGF)，granulocyte macrophage colony stimulating factor （GM-CSF），IFN-c，granulocyte colony stimulating factor （G-CSF），IFN-cinducible protein （IP）-10，monocyte chemoattractant protein（MCP）-1，macrophage inflammatory protein-1a （MIP1A），plateletderived growth factor （PDGF），tumor necrosis factor （TNF）-a，and vascular endothelial growth factor （VEGF）significantly increased[60，61].IL-6 elevation was significant in critically ill or nonsurvival patients[2，62–64].Anti-inflammatory treatment—including glucocorticoids，Tocilizumab（recombinant human IL-6 monoclonal antibody），Baricitinib （Janus kinase (JAK）inhibitor），chloroquine，and hydroxychloroquine—has been employed in clinics and was shown to be effective in reducing fever and the exacerbation of pneumonia，promoting the absorption of pneumonia，obtaining better oxygenation，improving lung imaging findings，and increasing the negative rate of virus nucleic acid testing[65].Compelling evidence has revealed that，when used to treat COVID-19，CHMs and their active ingredients can suppresspro-inflammatory cytokines and thus relieve cytokine storm in COVID-19 patients.Li et al.[32]showed that Lianhua Qingwen capsule markedly reduced the production of TNF-a，IL-6，C–C motif chemokine ligand（CCL)-2/MCP-1，and chemokine （C–X–C motif）ligand(CXCL）-10/IP-10 in a concentration-dependent manner in SARS-Co V-2-infected Huh-7 cells at the messenger RNA（m RNA）level.Ethanol extract of Lonicerae Japonicae Flos increased nuclear specificity protein 1（Sp1）binding activity and thereby enhanced the expression of IL-10，while decreasing nuclear factor（NF)-j B binding activity and thereby inhibiting the expression of TNF-a，IL-1b，and IL-6 in acute lung inflammation induced by lipopolysaccharide（LPS）in mice[33].Platycodin D（Platycodi Radix）improved the acute lung injury induced by LPS or bleomycin by suppressing apoptosis(caspase（CASP）-3 and Bax down-regulated）and inflammation（decreased TNF-a，IL-6，and NF-j B）and strengthening anti-oxidation（decreased myeloperoxidase（MPO）activity and improved superoxide dismutase activity）[34].Extract of Moutan Cortex Radicis also improved LPS-induced acute lung injury in rats by reducing IL-1b，MIP-2，IL-6，and MOP activity[35].Polysaccharides of Pinelliae Rhizoma exhibited significant suppression of LPS-induced airway inflammation by regulating levels of IL-4 and IFN-c and inhibiting mucus secretion in human airway epithelial human lung carcinoma cell292（NCI-H292）cells[36].It has been reported that quercetin，kaempferol，luteolin，isorhamnetin，baicalein，naringenin，and wogonin could be the main active ingredients of CHM for the management of COVID-19 by inhibiting inflammatory mediators，regulating immunity，and eliminating free radicals.These ingredients target IL-17，arachidonic acid，hypoxia inducible factor （HIF）-1，NF-j B，RAS，and TNF through cyclooxygenase （COX）-2，CASP-3，IL-6，MAPK1，MAPK14，MAPK8，and Rel A in the signaling pathways[54].