Synergistic antifungal activity of the lipophilic fraction of Hypericum carinatum and fluconazole

Abstract

Hypericum species, Hypericaceae, are recognized as a source of therapeutical agents. Purified fractionsand isolated compounds have been shown antimicrobial activity. As the indiscriminate use of antifungalsand the increase of infections caused by emerging species are leading to the search of new alterna-tive treatments, the aim of this study was to continue the study with Hypericum carinatum Griseb.lipophilic fraction, rich in phloroglucinol derivatives, investigating the effect of its association with flu-conazole against emerging yeasts (Candida krusei, C. famata, C. parapsilosis and Cryptococcus neoformans).The synergistic activity between H. carinatum lipophilic fraction and fluconazole was assessed by twomethodologies for multiple dose–response analysis: checkerboard and isobologram. Regarding syner-gistic experiments, the effect of the association was higher than the effect of fluconazole alone againstCandida krusei and C. famata isolates (MIC fluconazole decreased about eight and four folds, respectively),suggesting that, somehow, H. carinatum lipophilic fraction compounds are facilitating the action of thisdrug. On the other hand, when tested against Cryptococcus neoformans and C. parapsilosis, fluconazoleshowed better results than the association. Thus, against Candida krusei and C. famata, the lipophilicfraction of H. carinatum was able to reduce the MIC values of fluconazole and could be considered as apotential alternative to be used against emerging yeast species.