Antifungal activity of Uncaria tomentosa (Willd.) D.C. against resistant non-albicans Candida isolates

Abstract This study investigated in vitro antifungal activity of the hydroethanolic extract (EXT), quinovic acid glycosides (QAPF), oxindole alkaloids (OAPF), water-soluble (WSF) and insoluble fractions of polyphenols (WIF) obtained from Uncaria tomentosa bark against non- albicans Candida resistant isolates. Cytotoxicity and genotoxicity of the major fractions were also assayed. Growth inhibition was assayed by the broth microdilution method according to the CLSI M27-A3 guideline. The most active fractions were evaluated regarding cell ultrastructure, sorbitol metabolism, and infrared (FT-IR) analysis of pseudomycelia of C. krusei , C. glabrata and C. parapsilosis . Fluconazole, terbinafine and anidulafungin were used as reference drugs. EXT and all fractions were able to inhibit non- albicans C. growth at concentrations ranging from 500 to 3.9 mg/L. Nonetheless, the WIF showed the best in vitro anti- Candida activity (3.9 mg/L–15.62 mg/L). This fraction was composed mainly by high molecular mass polyphenols (70.8%) and, to a lesser extent, oxindole alkaloids (7.9%) and quinovic acid derivatives (7.8%). No significant cytotoxicity and genotoxicity was seen. As observed by scanning electron microscopy (SEM), yeasts treated with WIF presented morphological alterations and loss of integrity of the cell wall. The U. tomentosa water-insoluble fraction (WIF), composed mostly by high molecular mass polyphenols, showed significant antifungal activity in several non- albicans species, among them isolates resistant to terbinafine, fluconazole and anidulafungin. Noticeable microscopic and physicochemical changes in the cell wall indicated that it was the main target of this activity.