Synergistic Antimycobacterial Actions ofKnowltonia vesicatoria(L.f) Sims

Abstract

Euclea natalensisA.DC.,Knowltonia vesicatoria(L.f) Sims, andPelargonium sidoidesDC. are South African plants traditionally used to treat tuberculosis. Extracts from these plants were used in combination with isoniazid (INH) to investigate the possibility of synergy with respect to antimycobacterial activity. The ethanol extract ofK. vesicatoriawas subjected to fractionation to identify the active compounds. The activity of theKnowltoniaextract remained superior to the fractions with a minimum inhibitory concentration (MIC) of 625.0 μg/mL againstMycobacterium smegmatisand an MIC of 50.00 μg/mL againstM. tuberculosis. TheK. vesicatoriaextract was tested against two different drug-resistant strains ofM. tuberculosis, which resulted in an MIC of 50.00 μg/mL on both strains. The combination ofK. vesicatoriawith INH exhibited the best synergistic antimycobacterial activity with a fractional inhibitory concentration index of 0.25 (a combined concentration of 6.28 μg/mL). A fifty percent inhibitory concentration of this combination against U937 cells was 121.0 μg/mL. Two compounds, stigmasta-5,23-dien-3-ol (1) and 5-(hydroxymethyl)furan-2(5H)-one (2), were isolated fromK. vesicatoriaas the first report of isolation for both compounds from this plant and the first report of antimycobacterial activity. Compound (1) was active against drug-sensitiveM. tuberculosiswith an MIC of 50.00 μg/mL.