The polypeptide was extracted and purified from Moschus.In vitro cell model was used to screen polypeptide components from Moschus with anti-inflammatory activity,and to study the protective effect and mechanisms of Musk polypeptide on acute lung injury in mice.Five components (SXP1,SXP2,SXP3,SXP4,and SXP5) were extracted from Moschus by ultrasonic cell crusher and purified by ion-exchange chromatography.In LPS-induced THP-1 macrophages,SXP4 (100 μg/mL) manifested anti-inflammatory activity,which could significantly suppress the production of TNF-α and IL-1β. The SDS-PAGE results suggested that the molecule weight of polypeptide in SXP4 was most distributed within 10-26 kDa.In LPS-induced acute lung injury of the mice,SXP4 (5,15,50 mg/kg) could suppress the release of TNF-α and IL-6 in serum (P<0.05 or P<0.01),reduce inflammatory cell infiltration,improve the thickening of the alveolar wall,and alleviate the pathological damage in the lungs.Moreover,SXP4 could decrease IL-1β,IL-18 production and inhibit protein levels of NLRP3,ASC,and Caspase-1 in the lungs of mice with acute lung injury (P<0.01).In conclusion,polypeptide from Moschus (named SXP4) showed anti-inflammatory activity,which could alleviate pathological damage in the lungs of mice with acute lung injury that might be involved in the suppression of NLRP3/Caspase-1 mediated pyroptosis.