Qingfei Liyan Decoction Ameliorates Lipopolysaccharide-induced Acute Lung Injury by Synergistically Inhibiting the Cyclic GMP-AMP Synthase-Stimulator of Interferon Gene Pathway and Inflammasomes

Abstract Objective: Acute lung injury (ALI) is a life-threatening respiratory disorder and a major concern in modern medical research. Clinical research has shown that Qingfei Liyan Decoction (QFLYT), a formula based on Yin Qiao San, is used to treat lung-associated inflammatory diseases. However, the mechanism through which QFLYT exerts its therapeutic effects remains unclear. The purpose of this study was to evaluate the effects of QFLYT on lipopolysaccharide (LPS)-induced ALI and investigate the underlying molecular mechanisms. Materials and Methods: We established an ALI model by administering LPS drops into the trachea of mice. Bronchoalveolar lavage fluid (BALF) and lung tissue were collected to determine inflammatory indices. The effects of QFLYT and its single herbs on the cyclic GMP-AMP synthase-stimulator of interferon gene (cGAS-STING) pathway and inflammasomes were studied in vitro . Relevant proteins and factors were detected using the enzyme linked immunosorbent assay, real-time quantitative polymerase chain reaction, and Western blotting. Results: QFLYT reduced the secretion of inflammatory factors in BALF and lung tissue, and attenuated pathological damage to the latter. In addition, QFLYT inhibited multiple stimuli-induced cGAS-STING pathway and inflammasomes activation in vitro . Further investigation revealed that the herbs in QFLYT had no combined effects on the activation of the two pathways at their formulated doses. However, Forsythiae fructus, Lonicerae japonicae flos, and Licorice inhibited the activation of both pathways at higher concentrations. Conclusions: Our findings show that QFLYT ameliorates LPS-induced ALI by inhibiting the cGAS-STING pathway and inflammasomes.