Phytochemical Profile, Acute Toxicity, and Fluconazole-modulating Antifungal Activity of Stem and Barck Extracts of Adansonia digitata L. (Bombacaceae) against Nakaseomyces glabratus Isolates in Côte d’Ivoire

Abstract

Background &Aim: Nakaseomyces glabratus (formerly Candida glabrata) is an opportunistic yeast associated with invasive candidiasis and reduced susceptibility to azole antifungals. Plant-derived extracts are being investigated as potential modulators of antifungal activity, but evidence depends on the fungal strain, extract composition, and experimental method. This study evaluated the phytochemical profile, safety, in vitro antifungal activity, and interaction with fluconazole of aqueous and hydroethanolic extracts prepared from the stem and root bark of Adansonia digitata against N. glabratus isolates in Côte d’Ivoire. Materials: Four extracts were evaluated: aqueous stem (EAET) and root (EAER) bark, and hydroethanolic stem (EOHET) and root (EOHER) bark. Antifungal activity was assessed against two N. glabratus strains using agar incorporation and 2% glucose RPMI microdilution. Fluconazole-extract interactions were assessed by checkerboard testing and the fractional inhibitory concentration index (FICI). Acute oral toxicity was assessed after a single 5,000 mg/kg dose in female rats. Results: Phytochemical screening revealed sterols and polyterpenes, polyphenols, flavonoids, alkaloids, and tannins. Aqueous extracts showed lower MICs than hydroethanolic extracts in the agar-incorporation assay (125 versus 1,000 mg/mL for both strains). Corresponding MFCs were 500 and 1,000 mg/mL, with MFC/MIC ratios of 4 and 1. In combination with extracts, fluconazole MIC decreased from 8 to 4 mg/L for the reference strain and from 4 to 1 mg/L for the clinical isolate. FICI values ranged from 0.52 to 0.83 for the reference strain (additive) and from 0.26 to 0.33 for the clinical isolate (synergistic) under the prespecified thresholds. No mortality or major clinical signs were observed at 5,000 mg/kg; however, ASAT activity was significantly altered in the EOHET group. Conclusion: Aqueous extracts showed greater inhibitory potency, whereas hydroethanolic extracts showed a lower MFC/MIC ratio. The interaction with fluconazole was isolate-dependent, ranging from additive to synergistic. These preliminary in vitro findings, obtained from two strains, do not establish clinical efficacy or therapeutic applicability. Larger isolate panels, quantitative chemical profiling, mechanistic studies, reproducibility assessment, and appropriately designed in vivo studies are required.