Evaluation of in vitro Antifungal Activity of Xylosma prockia (Turcz.) Turcz. (Salicaceae) Leaves Against Cryptococcus spp.

Abstract

Cryptococcus species are responsible for important systemic mycosis and are estimated to cause millions of new cases annually. The available therapy is limited due to the high toxicity and the increasing rates of yeast resistance to antifungal drugs. Popularly known as "sucará," Xylosma prockia (Turcz.) Turcz. (Salicaceae) is a native plant from Brazil with little information on its pharmacological potential. In this work, we evaluated in vitro anticryptococcal effects of the leaf ethanolic extract of X. prockia and its fractions against Cryptococcus gattii and Cryptococcus neoformans. We also evaluated phenotypic alterations caused by ethyl acetate fraction (EAF) (chosen according to its biological results). The liquid chromatography-mass spectrometry (LC-MS) analysis of EAF demonstrated the presence of phenolic metabolites that belong to three structurally related groups as majority compounds: caffeoylquinic acid, coumaroylglucoside, and caffeoyl-glucoside/deoxyhexosyl-caffeoyl glucoside derivatives. The minimum inhibitory concentration (MIC) values against C. gattii and C. neoformans ranged from 8 to 64 mg/L and from 0.5 to 8 mg/L, for ethanolic extract and EAF, respectively. The EAF triggered an oxidative burst and promoted lipid peroxidation. EAF also induced a reduction of ergosterol content in the pathogen cell membrane. These effects were not associated with alterations in the cell surface charge or in the thermodynamic fingerprint of the molecular interaction between EAF and the yeasts evaluated. Cytotoxic experiments with peripheral blood mononuclear cells (PBMCs) demonstrated that EAF was more selective for yeasts than was PBMCs. The results may provide evidence that X. prockia leaf extract might indeed be a potential source of antifungal agents.

Emerging Antifungal Targets and Strategies

“…These cells are called “titan cells”, and, due to their large size, including their capsule, they obstruct the removal by the immune system [ 125 ]. According to the study by Folly et al [ 95 ], the antifungal activity of Xylosma prockia leaf ethanolic extract and its fractions was investigated for the first time against C. neoformans and C. gattii . In the mentioned study, morphometric analysis showed that ethyl acetate fraction induces reduced surface/volume ratio for C. gattii and C. neoformans while also reducing the levels of ergosterol in the fungal cell membrane.…”