Title

 

Authors

T. Rossi¹, A.I. Ruberto¹, L. Baroni¹, E. Bortolazzi¹ and A. Fabio². 

University of Modena and Reggio Emilia, ¹Dept of Biomedical Sciences, Section of Pharmacology, Via G. Campi 287, Modena, ²Dept of Medicine Laboratory, Via del Pozzo 71; Modena, Italy 

 

Abstract

Candidiasis is a very common fungal disease but the real problem is the presence of resistant strains which may ineffective the treatments usually performed with drugs characterised by severe side effects. New, non toxic and active compounds are needed to oppose candidiasis, a pathology more and more evident both in HIV-positive and HIV-negative people (Armstrong 2007) Recent studies performed in our laboratories showed an interesting anti-oxidative activity displayed by the flavone glabridin; moreover scientific literature demonstrated that flavones can modulate the biosynthesis of endogenous sterols and injure the fungal membrane whose integrity is crucial for fungal agent’s survival (Nerya et al., 2003). Based on this knowledge, we investigatedon the antifungal activity of the flavone glabridin. Materials and Methods: Five multi-resistant strains of Candida (albicans, parapsilosis, krusei, glabrata, tropicalis) fromclinical specimens from HIV-seropositive subjectskindly supplied by the Department of Medicine Laboratory-Ospedale Policlinico Modena, were cultured in Sabouraud Dextrose Liquid Medium (pH 5,6 ± 0,2 at 25°C) and treated with increasing concentrations (from 5 µM to 0.16 µM) of glabridin.Fluconazole was chosen as reference drug. Sensitivity tests were performed in according with the NCCLS method for agar dilution and MIC values (minimal inhibitory concentration) were calculated both for glabridin and for fluconazole. Fluconazole was added at concentrations varying from 654 microM/l to 0.3 microM/l. Results: As expected (Charlier et al., 2006), no antifungal activity was evident in cultures treated with fluconazole (strains were multiresistant and MIC values resulted >100mg/L) while, very interesting results came from the cultures treated with glabridin. The comparison of MIC values shows that two strains: C. albicansand C. kruseiare sensitive to glabridin: MICs 1.25 microM/land1.87 microM/lrespectively while fluconazole MICs on the same strains were327microM/land654microM/l.The FIC index used to estimate the interactions outcomes was also calculated. The association glabridin/fluconazole result never in synergism nor in antagonism.Conclusion. Preliminary results from the present study and those obtained from the investigations on cytotoxicity and the antioxidative effects lead to the following considerations: glabridin displays several positive activities; it is non toxic on keratinocites, prevents oxidative DNA damage from UVB radiation, is active at low concentrations against multiresistant Candidae strains. We conclude that it must be considered forconsidered further investigations since it could represent a new, non toxic natural active principle to include among skin photoprotective agents with promising applications in dermatological clinical research.

Armstrong (2007). J Antimicrob Ther. 60: 459-60.
Nerya et al (2003). Agric. Food. Chem. 51: 1201-7.
Charlier et al.(2006).JAC.57: 384-410.