Abstract

This study was designed to investigate the antifungal activity of a hydroalcoholic extract from Flos Rosae Chinensis (FRC) combined with fluconazole (FCZ) against clinical isolates of Candida albicans resistant to FCZ. The minimum inhibitory concentration (MIC) of FRC was determined using a checkerboard microdilution assay. The synergistic effects of the combination of FRC and FCZ against clinical isolates of C. albicans resistant to FCZ were further confirmed by constructing time-growth curves and performing an agar diffusion test. FRC alone exerted efficient antifungal activities against C. albicans within a MIC80 ranging from 20 μg/ml to 40 μg/ml. FRC failed to enhance the effects of FCZ against sensitive C. albicans strains, although it rendered FCZ-resistant C. albicans more sensitive. These results were further confirmed by the result of in vivo study. Our study is the first to discover that FRC can inhibit the growth of C. albicans to a certain degree. An FRC antifungal mechanism study showed that FRC strengthens FCZ to inhibit the action of ergosterol biosynthesis by promoting the transformation of lanosterol to eburicol, suggesting that the antifungal mechanism of FRC involves the inhibition of ergosterol biosynthesis.

Highlights

  • In the modern society, with the increasing use of cancer chemotherapy, organ transplantation, and hematopathy and the increased incidence of diabetes and diseases of aging, broad-spectrum antibiotics, adrenal cortical hormone, cytotoxic drugs, and immunosuppressants have been clinically applied in an unreasonable manner for a long time

  • The FCZFRC combination markedly reduced the MIC80 required for FCZ-resistant C. albicans (Table 1)

  • In addition to C. albicans, synergism was observed for C. parapsilosis 160

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Summary

Introduction

With the increasing use of cancer chemotherapy, organ transplantation, and hematopathy and the increased incidence of diabetes and diseases of aging, broad-spectrum antibiotics, adrenal cortical hormone, cytotoxic drugs, and immunosuppressants have been clinically applied in an unreasonable manner for a long time. With the increasing use of FCZ, drug-resistant strains are emerging rapidly [4,5,6]. How to exploit new antifungal drugs or to identify non-resistance-forming methods of killing C. albicans remains one of the hottest issues in antifungal research. It is known that a variety of Chinese herbal medicines exert activities against pathogenic microorganisms [7,8,9,10,11]. Studies at our research center have shown that baicalein [16], berberine [17], and tetrandrine [18] could enhance the antifungal activity of FCZ against FCZresistant C. albicans. Our study was conducted to identify new compounds from Chinese herbal medicines that can synergistically potentiate the inhibitory effects of FCZ on the growth of C. albicans

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