The pathogenic hyper-inflammatory response has been revealed as the major cause of the severity and death of the Corona Virus Disease 2019 (COVID-19). Xuanfei Baidu Decoction (XFBD) as one of the "three medicines and three prescriptions" for the clinically effective treatment of COVID-19 in China, shows unique advantages in the control of symptomatic transition from moderate to severe disease states. However, the roles of XFBD to against hyper-inflammatory response and its mechanism remain unclear. Here, we established acute lung injury (ALI) model induced by lipopolysaccharide (LPS), presenting a hyperinflammatory process to explore the pharmacodynamic effect and molecular mechanism of XFBD on ALI. The in vitro experiments demonstrated that XFBD inhibited the secretion of IL-6 and TNF-α and iNOS activity in LPS-stimulated RAW264.7 macrophages. In vivo, we confirmed that XFBD improved pulmonary injury via down-regulating the expression of proinflammatory cytokines such as IL-6, TNF-α and IL1-β as well as macrophages and neutrophils infiltration in LPS-induced ALI mice. Mechanically, we revealed that XFBD treated LPS-induced acute lung injury through PD-1/IL17A pathway which regulates the infiltration of neutrophils and macrophages. Additionally, one major compound from XFBD, i.e. glycyrrhizic acid, shows a high binding affinity with IL17A. In conclusion, we demonstrated the therapeutic effects of XFBD, which provides the immune foundations of XFBD and fatherly support its clinical applications.
Keywords: Acteoside (PubChem CID: 5281800); Acute lung injury; Amygdalin (PubChem CID: 656516); COVID-19; Ephedrine (PubChem CID: 9294); Glycyrrhizic acid (PubChem CID: 14982); Hastatoside (PubChem CID: 92043450); Liquiritin (PubChem CID: 503737); Naringin (PubChem CID: 442428); PD-1/IL17A pathway; Polydatin (PubChem CID: 5281718); Sinapine (PubChem CID: 5280385); Systematic network pharmacological analysis; Verbenalin (PubChem CID: 73467); Xuanfei Baidu Decoction.
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