Antifungal Activities of Phytochemically Characterized Hydroethanolic Extracts of Sclerocarya birrea Leaves and Stem Bark against Fluconazole-Resistant Candida albicans Strains

Abstract

The study evaluated the antifungal activities of the 70% ethanol extracts of Sclerocarya birrea leaves (SBL) and stem bark (SBB) against C. albicans strains and fluconazole-resistant isolates, their antifungal effects in combination with conventional antifungals as well as their effects on the biofilms of the C. albicans strains and isolates. UPLC-QTOF-MS/MS analysis was then carried out to investigate the metabolite profile of the extracts and UPLC fingerprints developed for their routine identification as part of quality control measures. The extracts exhibited considerable antifungal activity with MIC ranging from 12.21 to 97.66 μg/mL and MFC from 12.21 to 390.63 μg/mL against the C. albicans strains and isolates. The antifungal activity of the stem bark extract was higher than the leaf extract. SBL and SBB also significantly inhibited biofilm formation ( $\text{I}{\text{C}}_{50}=12.49$ to 164.42 μg/mL) and the mature biofilms ( $\text{I}{\text{C}}_{50}=91.50$ to 685.20 μg/mL) of the strains and isolates of the C. albicans and demonstrated potential for their use in combination therapies with currently used antifungals especially the stem bark extract with nystatin. Metabolite profiling identified the presence of polyphenolic compounds in both leaves and stem bark mostly flavonoids, their derivatives, and proanthocyanidins, which contribute in part to the bioactivity of the plant. Whereas flavonoids like quercetin, myricetin, and their derivatives were abundant in the leaves, epicatechin monomers with their condensed tannins, including procyanidin B2 and procyanidin C, were abundant in the stem bark. Fingerprints of SBL and SBB were developed and validated and could be used as qualitative tools to authenticate the plant. The outcomes of the study show the promise of the leaf and stem bark extracts of S. birrea to be studied further and developed as antifungal agents.