The antifungal effect of kaempferol in the G.mellonella larvae-Candida albicans infection model
LIU Peng
FAN Ming
HAN Bing
WANG Xiaojuan
Abstract：Objective To evaluate the in vitro antifungal activity and to assess the in vivo therapeutic effect of kaempferol against Candida albicans infection in G.mellonella larvae model.Methods We detected the minimum inhibitory concentration(MIC80)of kaempferol(KAE)against C.albicans SC5314.And,the fractional inhibitory concentration index(FICI)of the combination of KAE and fluconazole(FLC)on clinical isolated FLC-resistant C.albicans was detected by checkerboard micro liquid-based dilution method.Next,we observed the effect of KAE on hyphae formation of C.albicans SC5314 induced by RPMI1640 or Spider medium.Moreover,the influences of KAE on C.albicans SC5314 biofilm formation was determine using the XTT assay.Further,we ascertained the expression levels of genes related to Candida albicans SC5314 adherence,hyphae induction,and biofilm formation treated with KAE by real time RT-PCR.Finally,the in vivo therapeutic efficacy of KAE was investigated by using the G.mellonella larvae-C.albicans SC5314 infection model,calculating the survival rate,the colony-forming units(CFU),and pathological staining.Results The MIC80 of KAE against C.albicans SC5314 was 128 μg/mL.KAE had a significant synergistic anti-FLC-resistant C.albicans activities in combination with FLC,which reduced the MIC80 of FLC in a range of 32 to 512-fold,and the MIC80 was between 0.25～4 μg/mL.160 μg/mL of KAE inhibited C.albicans 5314 hyphae growth,biofilm formation,and suppressed the expression of CSH1,ALS1,SAP5,HWP1,BCR1,EFG1,and HGC1 genes expression,and activated the expression of NRG1 and TUP1.The results of the G.mellonella larvae infection model revealed that the median survival time of the saline-administered group was 36 h,and the histopathological PAS staining showed significant fungal hyphae or yeast.KAE showed a concentration-dependent theraputic effect.The 4 mg/kg KAE increased the survival rate of larvae up to 30%,markedly reduced the CFUs and ameliorated pathologic damage and melanization.Conclusions KAE has a certain in vitro and in vivo anti-C.albicans activity,and the mechanisms involved are probably by inhibiting the hyphae and biofilm formation.
Keywords：Candida albicansG.mellonella larvaekaempferolin vivo antifungal activity
Publication Date：2025-02-28
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：7( 14-19,27 )