The aim of the present study was to evaluate the in vitro activity of baicalein, the flavone constituent of Scutellaria baicalensis, and synergism of the combination of baicalein and fluconazole against Candida albicans, Candida tropicalis and Candida parapsilosis. The MIC 50 (lowest concentration at which there was 50 % inhibition of growth) of baicalein alone against six Candida strains ranged from 13 to 104 mg ml "1 . For the three species tested, exposure to baicalein at the MIC 50 concentrations obtained for each strain resulted in a high loss of viability. The fluconazole plus baicalein combination markedly reduced the MICs of both drugs for all three strains analysed. In addition, a synergistic effect between baicalein and fluconazole was observed for C. parapsilosis in terms of MIC 50 (fractional inhibitory concentration index50.207). Scanning electron microscopy analysis revealed that yeast cells exposed to baicalein at MIC 50 produced a profusely flocculent extracellular material, resembling a biofilm-like structure. In conclusion, these results showed the antifungal capability of baicalein against Candida species and highlight a promising role of baicalein when used in combination with fluconazole against Candida infections.
INTRODUCTIONCandidiasis is one of the most common fungal infections in humans caused by Candida species, most notably by Candida albicans. Currently, other species of this genus have been found to cause an increasing number of cases of candidiasis (Mokaddas et al., 2007;Pereira et al., 2010;Das et al., 2011).The therapy of invasive candidiasis remains a difficult medical problem. Despite the availability of extendedspectrum triazoles, the incidence of invasive infections and resistance to antifungal therapy continue to increase (Pfaller & Diekema, 2010). Widespread use of antifungal agents could be an explanation for the emergence of the more resistant non-albicans species of Candida, such as Candida glabrata (reviewed by Kothavade et al., 2010; Silva et al., 2012).The azole fluconazole is effective against most Candida species and is used currently as a first-line drug, although different degrees of susceptibility among species have been described. For instance, C. glabrata is inherently less susceptible to fluconazole. In addition, the emergence of fluconazole resistance has been reported in species typically susceptible to this agent, such as C. albicans, Candida tropicalis and Candida parapsilosis (Hajjeh et al., 2004;Yang et al., 2004;Lyon et al., 2010;Oxman et al., 2010; Arendrup et al., 2011), including that observed in Brazilian tertiarycare hospitals (Bruder-Nascimento et al., 2010;Favalessa et al., 2010;Pereira et al., 2010;Furlaneto et al., 2011).These factors present an urgent need to search for novel compounds with anticandidal activity. To this end, efforts have been made in the search for novel antifungal agents from various natural sources. In this regard, baicalein (5,6,7-trihydroxyflavone; Fig. 1) is a flavonoid originally isolated from the roots of the Chine...