Activity of Fabaceae species extracts against fungi and Leishmania: vatacarpan as a novel potent anti-Candida agent

AbstractLeishmaniasis and fungal infection treatment efficacy is limited by toxicity and ever increasing resistance to available drugs, requiring development of alternative compounds. The richness of Cerrado plant antimicrobial secondary metabolites justifies screening of Fabaceae species extracts: Enterolobium ellipticum Benth., Sclerolobium aureum (Tul.) Baill. and Vatairea macrocarpa(Benth.) Ducke, against Leishmania(Leishmania) amazonensis, yeasts and dermatophytes. Among the 26 extracts tested, more than 50% of the total demonstrated significant antifungal activity in comparison to the drug controls (minimal inhibitory concentration 0.12 to ≤31.25 µg/ml). Six extracts capable of complete parasitic growth inhibition had the inhibitory concentration index for 50% values from 9.23 to 78.65 µg/ml. The results led to the selection of the V. macrocarpa ethyl acetate root bark extract for chemical fractionation. This plant, traditionally referred to as angelim-do-cerrado or maleiteira, is used to treat superficial mycoses in Amazonia. A previously unreported pterocarpan vatacarpan together with the known compound musizin was isolated. Vatacarpan demonstrated a minimal inhibitory concentration value of 0.98 µg/ml against Candida albicans ATCC 10231, and thus comparable or superior to fluconazole and amphotericin B. The results add to literature's information the ability of pterocarpans to act as antimicrobial agents.

Hippocratic screening and subchronic oral toxicity assessments of the methanol extract of Vatairea macrocarpa heartwood in rodents

Vatairea macrocarpa (Benth.) Ducke, Fabaceae, is popularly known as 'angelim'. Its heartwood macerate is used to treat inflammation, gastric ulcer, diabetes and infections. The oral acute and subchronic toxicity of the methanol extract of V. macrocarpa heartwood (MEVm) was evaluated. In the Hippocratic screening, a single administration of MEVm was given orally to mice at doses ranging from 100 to 5000 mg/kg. In the subchronic study, MEVm was given orally as a daily administration for thirty days to Wistar rats at doses of 20, 100 and 500 mg/kg. In Hippocrtaic screening, doses of MEVm up to 5000 mg/kg did not cause any relevant behavioral changes or deaths thus making it impossible to establish the LD50. In subchronic assay, body weight gains and food intake were significantly reduced at the last week of treatment with 20 and 500 mg/kg dose. Serum triacylglycerides, total proteins and γ-glutamyltransferase activity were significantly reduced, while alkaline phosphatase activity was elevated. In hematological parameters, MEVm increased the percentage of segmented neutrophils cells at the highest dose. All alterations observed were minor in nature and were not accompanied by any relevant clinical signs or any histopathological changes. In conclusion, the results demonstrate relative safety profile of MEVm in the experimental animals.