Abstract: This study aimed to investigate the synergistic effect of selaginellin on azoles against Candidasis and to explore the related mechanism.Checkerboard microdilution method was used to study the antifungal activities of selaginellin in combination with fluconazole (FLC) or ketoconazole (KEC) against Candidasis.Fractional inhibitory concentration index (FICI) was employed as the interpretation standard.Synergistic effects were showed by SEL in combination with FLC and KEC against Candida albicans,C.parapsilosiswith FICI of 0.5.However,no synergy was found for SEL and FLC or KEC against C.kruser.mRNA expressions of related genes in C.albicans were assayed by quantitative real time PCR (qRT-PCR).SEL exhibited reversal effect on the upregulated expressions of ERG5,ERG11,CDR1,CDR2,MDR1,FLU1,SIR2 by 86%,71%,62%,67%,56%,36% and 52% induced by FCL in C.albicans.Furthermore,the expression of Sir2 was detected by Western-blot,and likewise,SEL displayed reversal effect on the upregulated expressions of Sir2 induced by FCL.These results indicated that SEL had the in vitro effect to enhance the activities of FLC and KEC against C.albicans and C.parapsilosis.

Key words: selaginellin, fluconazole, ketoconazole, Candidasis, synergistic effects, checkerboard microdilution method