Hindawi Publishing Corporation Evidence-Based Complementary and Alternative Medicine Volume 2012, Article ID 808979, 9 pages doi:10.1155/2012/808979 Research Article Synergistic Antimycobacterial Actions of Knowltonia vesicatoria (L.f) Sims Antoinette Labuschagn´ e, 1 Ahmed A. Hussein, 1, 2 Benjam´ ın Rodr´ ıguez, 3 and Namrita Lall 1 1 Department of Plant Science, University of Pretoria, Gauteng Pretoria 0002, South Africa 2 Department of Chemistry of Medicinal Plants, National Research Center, El-Tahrir Street, Dokki, Cairo 12311, Egypt 3 Instituto de Qu´ ımica Org´ anica, Consejo Superior de Investigaciones Cient´ ıficas (CSIC), Juan de la Cierva 3, 28006 Madrid, Spain Correspondence should be addressed to Namrita Lall, namrita.lall@up.ac.za Received 18 January 2012; Accepted 19 February 2012 Academic Editor: Victor Kuete Copyright © 2012 Antoinette Labuschagn´ e et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Euclea natalensis A.DC., Knowltonia vesicatoria (L.f) Sims, and Pelargonium sidoides DC. 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 of K. vesicatoria was subjected to fractionation to identify the active compounds. The activity of the Knowltonia extract remained superior to the fractions with a minimum inhibitory concentration (MIC) of 625.0 μg/mL against Mycobacterium smegmatis and an MIC of 50.00 μg/mL against M. tuberculosis. The K. vesicatoria extract was tested against two different drug-resistant strains of M. tuberculosis, which resulted in an MIC of 50.00 μg/mL on both strains. The combination of K. vesicatoria with 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 from K. vesicatoria as the first report of isolation for both compounds from this plant and the first report of antimycobacterial activity. Compound (1) was active against drug-sensitive M. tuberculosis with an MIC of 50.00 μg/mL. 1. Introduction For the last 40 years there has been little progress in the treatment of Tuberculosis (TB). The standard albeit dated treatment regime is strict and lengthy (6–9 months) resulting in adverse side effects and inevitable patient noncompliance. It is no surprise that the emergence of multiple and exten- sively drug resistant strains of Mycobacterium tuberculosis (M. tb) is on the rise. The WHO recently reported that in some areas of the world, one in four people with TB becomes ill with a form of the disease that can no longer be treated with standard drugs [1]. In addition, HIV/AIDS increases the risk for developing active TB and renders TB difficult to diagnose and treat. The TB-HIV/AIDS coinfection rate in South Africa is distressingly high, with an estimated 73 percent of new TB patients coinfected with HIV [2]. The search for new TB treatments that are effective against resistant strains of M. tb and treatments which can augment the potential of existing drugs against the disease is more important today than at any other time in history. Without the introduction of new treatments, TB patients will run out of options for effective drugs. Plant products have received considerable attention as potential anti-TB agents with a recent review emphasizing plant products as sources of antimycobacterial extracts and compounds [3]. Most traditionally used plant therapies rely for their effects on a variety of compounds and synergy between these compounds, however, there are numerous benefits for isolating and identifying active constituents from these bioactive plants. These benefits include characterising toxicity profiles, simpler determination of modes of action, and new activities of known compound which adds to the wealth of information on phytochemicals. Combining plant extracts and current TB drugs holds advantages such as decreased toxicity profiles, increased bioavailability