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Cnidii fructus is the dried ripe fruit of Cnidium monnieri(L.)Cusson.As a popular traditional Chinese medicinal herb,C.fructus has been used for the treatments of infection diseases such as suppurative dermatitis and pudendum itching.In this study,we first investigated the antifungal effects of C.fructus extract(CFE)and its major constituents: osthole,imperatorin,bergapten and isopimpinellin.Checkerboard microdilution assay demonstrated that CFE has significant synergistic effect with FLC against FLC-resistant C.albicans,in which osthole(OST)is the major bioactive component.Similar results was obtained from time kill curve assay.Meanwhile,XTT reduction assay demonstrated the synergism of FLC and OST against C.albicans biofilm formation.In addition,microarray results showed that the expression of genes involved in oxidation-reduction process,energy metabolism and transportation changed significantly after the combined treatment of FLC and OST,and further results demonstrated the marked augmentation of endogenous reactive oxygen species(ROS)in the combined treatment group.In conclusion,these results demonstrated the synergism of FLC and OST against FLC-resistant C.albicans and indicated that endogenous ROS augmentation might contribute to the synergism of FLC and OST.