Antifungal and multidrug resistance modulatory activities in extracts of medicinal plants

Disseminated fungal infections pose a serious therapeutic challenge especially in the group of patients with compromised immunity. This is related to the limited number of effective antifungals and results in high mortality rates. Of the two major human fungal pathogens Candida glabrata generally shows reduced susceptibility to the important class of azole antifungals, whereas Candida albicans often develops resistance during the course of the treatment. This is frequently related to increased efflux of antifungals via multidrug transporters of broad specificity of the ATP-binding cassette class, such as Cdr1p or Cdr2p. New antifungal treatments, especially those active against drug-resistant strains are needed. In this study a panel of extracts from medicinal plants traditionally used in the South and Southeast African regions was screened for their growth inhibitory activity against Candida albicans and Candida glabrata. The resulting MIC values, determined in growth assays using the microdilution procedure, demonstrate a potent anticandidal activity of several extracts. These include the extract of Litogyne gariepina and Anacardium occidentalis that showed increased activity against Candida glabrata (MIC in the range of 100µg/ml), a species showing reduced susceptibility to fluconazole, which was used as a positive control. Our observations indicate that this second most frequent human fungal pathogen should more often be included in natural product screening for antifungal activity. Further fractionation of selected crude extracts revealed the presence of effective non toxic modulators of Cdr1p activity in addition to its antifungal growth inhibitory substrates, illustrating the synergistic effect of antifungal medicinal plant components.

Acknowledgements: The authors thank the Science and Technology Foundation, Portugal (FCT, grant SFRH/BD/22321/2005) and the Ministry of Scientific Research and Information Technology (grant 2P05A 080 28 and funds for the Wrocław Medical University)