The effects of arctigenin (ARG) in acute lung injury (ALI) were investigated based on animal experiments in vivo,cell experiments in vitro,and molecular docking.The model of ALI in mice and NP-69 cell injury induced by lipopolysaccharide (LPS) were used.Western blot was used to detect the protein expression of Occludin and zonula occludens-1 (ZO-1) in the nasal mucosa of mice after nasal injury induced by LPS.The levels of inflammatory factors in the mouse alveolar lavage fluid were detected by ELISA.The wet/dry mass ratio of mouse lung tissue was measured to evaluate the degree of pulmonary edema.Lung histopathological changes in mice were observed by HE staining.The inflammatory injury model of NP-69 cells induced by LPS was used to detect the content of inflammatory factors in the cell supernatant to investigate the anti-inflammatory effects of ARG.The mRNA expression levels of ZO-1,human beta-defensin 3 (HBD3),interleukin-22 receptor subunit alpha-1 (IL-22Ra1),Janus kinase 1 (JAK1),tyrosine kinase 2 (Tyk2),and signal transducer and activator of transcription 1 (STAT1) were determined by RT-PCR.The protein expression of ZO-1,HBD3,IL-22Ra1,JAK1,p-JAK1,JAK1,Tyk2,STAT1 and p-STAT1 were detected by Western blot.Molecular docking techniques were used to predict the binding ability of ARG with related target proteins.The results showed that ARG significantly reduced the pulmonary edema and pathological changes in mice,reduced the levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β), and upregulated the protein expression of Occludin and ZO-1 in the mouse nasal mucosa.RT-PCR results showed that the epithelial barrier disrupted by LPS was alleviated after ARG treatment in vitro.Mechanistically,ARG upregulated the mRNA expression of ZO-1,HBD3,IL-22Ra1,JAK1,and TYK2,identically upregulated the protein expression levels of ZO-1,HBD3,IL-22Ra1,JAK1,p-JAK1,p-STAT1,and Tyk2.Molecular docking experiments showed that ARG has good affinity with TNF-α,JAK1,and STAT1.The above results indicate that ARG could alleviate acute lung injury by reducing inflammation,and promoting nasal mucosal epithelial barrier repair.Its mechanism is related to the activation of IL-22/JAK1/STAT1 signaling pathway.