Xuanfei Baidu Decoction reduces acute lung injury by regulating infiltration of neutrophils and macrophages via PD-1/IL17A pathway. (February 2022) - Wang, Yuying
Abstract: 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. Graphical Abstract: ga1 Highlights: Xuanfei Baidu Decoction is one of the "three medicines and three prescriptions" for the clinically effective treatment of COVID-19 in China. This paper provides the basic research of Xuanfei Baidu Decoction in acute lung injury model. We demonstrated that Xuanfei Baidu Decoction improved pulmonary edema, alveolar damage and hyperplasia at different time points (day 2 and day 5) after LPS infusion. We revealed that Xuanfei Baidu Decoction alleviated acute lung injury by inhibiting infiltration of macrophages and neutrophils and excessive inflammation through the PD-1/IL17A signaling pathway.