Eumycetoma and Plant-based Pharmacotherapy Candidates

Abstract

Mycetoma is a chronic, inflammatory, granulomatous infection that is present worldwide and endemic in tropical and subtropical regions, caused by the traumatic inoculation of a fungus (eumycetoma) or a bacterium (actinomycetoma). Sudan is famous for being an endemic area of mycetoma and may be the homeland of the disease with Gezira state of central Sudan, being the focal point. Medical treatment of eumycetoma by conventional antifungal therapies is quite disappointing. Surgical debridement may be necessary, and amputation is sometimes the only solution. This study was an attempt to find a safe cure of natural origin. The methanolic extracts of seven selected local plants were screened for their antimycetomal activity using the Microbroth Dilution method. All seven plant extracts were able to inhibit Madurella mycetomatis growth at a concentration of 50 µg/ml or less, point to an important property that for the first time to be disclosed. Three plant species out of the seven managed to inhibit the growth of Madurella mycetomatis at a concentration as low as 0.781 µg/ml; these were: Boswellia papyrifera, Acacia nubica and Nigella sativa. MICs of these extracts and /or fractions on 13 mycetoma strains were determined using the standard cellular viability XTT-assay. Results revealed that almost all extracts and fractions exhibited antifungal activity (MIC-50 = 1- 4µg/ml). The methanolic extract from the gum resin of Boswellia papyrifera exhibited the best potential anti-mycetoma activity. Boswellia extract was fractionated using different organic solvents of variant polarities, and was then biological tested; results showed presence of good anti-mycetomal activity in the crude methanol and the ethyl acetate fraction. Gas-Liquid-Chromatography hybrid Mass-Spectrophotometer (GC-MS) analysis of these fractions; showed the occurrence of four phytoconstituents, triterpenoid in nature: Beta-amyrin, Beta-amyrone, Beta-Sitosterol and Stigmatriene. Biological evaluation of these triterpenes against 12 Madurella mycetomatis strains revealed that each individual triterpene phytoconstituent had some anti-mycetoma activity, but Stigmatriene was the best to show anti-mycetoma activity at an MIC equal to 32 µg/ml. In conclusion these results are quite encouraging for further evaluation of crude extracts and the identified isolates which represent an important class of drugs that have potential for clinical use for prevention and treatment of eumycetoma and other invasive fungal infections.