Both community-associated and hospital-acquired infections with methicillin-resistant Staphylococcus aureus(MRSA)have been increasingly reported around the world in the past 20 years.In 2006,the Centers for Disease Control and Prevention(CDC)reported that 64%of MRSA isolates were of the USA300 clonal type in infected patients in USA.The aim of our study was to estimate the in vitro effect of imperatorin on MRSA strain BAA-1717(USA300).The effects of imperatorin on alpha-hemolysin(Hla)production,when strain BAA-1717 was co-cultured with sub-inhibitory concentrations of imperatorin,were analysed using susceptibility testing,hemolysis assays,western blotting and real-time PCR.Live/Dead analysis and cytotoxicity assays were employed to examine the protective effect of imperatorin against the strain BAA-1717-mediated injury of human alveolar epithelial cells(A549).The results showed that imperatorin has no anti-S.aureus activity at the tested concentrations in vitro.However,imperatorin can observably inhibit the production of Hla in culture supernatants and reduce the transcriptional levels of hla(the gene encoding Hla)and arg(the accessory gene regulator).Imperatorin prevented Hla-mediated A549 epithelial cell injury in a co-culture system.In conclusion,our results suggested that imperatorin has the potential to be developed as a new anti-virulence drug candidate for managing S.aureus infection.