Tuberculosis treatment is intrinsically associated with major challenges, such as complex and lengthy treatment. These have a direct impact on patient compliance and treatment outcome. Recently, there has been another concern regarding the increasing incidence of MDR and XDR tuberculosis[16]. As a result of the growing burden of drug-resistant genotypes of Mycobacterium tuberculosis coupled with TB-HIV coinfection, the burden of TB is now quite difficult to manage. Therefore, there is a global imperative to discover and develop new and efficacious antituberculosis agents, which should be an urgent biomedical priority[18, 19]. The plants selected in the current study are commonly used in Ugandan traditional medicine to treat tuberculosis and related ailments and have also been studied for their antimycobacterial activity against different strains of Mycobacterium tuberculosis[4, 10, 20]. However, little is known about the effects of combination of medicinal plants and conventional antituberculosis drugs.
This study is the first to report on the combination effect of Zanthoxylum leprieurii and Rubia cordifolia with standard antituberculosis drugs in Uganda. Previous studies have only focused on the antimycobacterial activities of these plants. It has been demonstrated that when used in combination, drugs with significantly low efficacy have therapeutic effects, even against drug-resistant strains[3]. Drug combination treatment has long been employed as a standard treatment strategy for many chronic diseases, including tuberculosis. With an objective to elucidate any potential synergistic interactions of the two commonly used medicinal plant extracts with standard first-line anti-TB drugs, we evaluated the antimycobacterial activity (percentage inhibition) of Z. leprieurii and R. cordifolia methanol extracts in combination with rifampicin, isoniazid, ethambutol and streptomycin against M. tuberculosis (H37Rv and MDR) strains.
Rifampicin alone exhibited 100% and 29% growth inhibition at 1 µg/mL against pansensitive H37Rv and MDR strains, respectively. On combination with Z. leprieurii and R. cordifolia extracts at a concentration of 50 µg/mL, an increase in growth inhibition was observed at 86% and 63% respectively against MDR-MTB. When each of the extracts at a concentration of 50% µg/mL was combined with isoniazid at 0.2 µg/mL, an additive effect was observed against the MDR- strain, resulting in 91% and 62% inhibition by Z. leprieurii and R. cordifolia against the MDR strain, respectively. The mechanism contributing to this synergistic effect against MDR strains is not yet known; however, there is a likelihood that since isoniazid inhibits mycolic acid synthesis, these plant extracts inhibit cell wall synthesis[3, 21].
All anti-TB drugs used in this study, rifampicin at 1 µg/mL, isoniazid at 0.2 µg/mL, ethambutol at 7.5 µg/mL and streptomycin at 2 µg/mL, exhibited a growth inhibition of not more than 52% against the MDR strain. However, a synergistic effect was observed when the standard drugs were combined with both extracts at even lower concentrations. They exhibited mycobacterial growth inhibition of between 62% and 100% against the MDR strain. This finding was consistent with other standard anti-TB drugs studied against MDR strains. This is in tandem with other previous studies that indicated that extracts of Z. leprieurii and R. cordifolia inhibited the growth of the MDR strain of Mycobacterium tuberculosis[4, 20, 22].
This study demonstrated that extracts of Z. leprieurii and R. cordifolia possess significant in vitro antimycobacterial activities against both pansensitive (H37Rv) and multidrug-resistant (MDR) MTB strains. Additionally, the extracts exhibited additive and/or synergistic interactions when combined with standard anti-tuberculosis drugs, more remarkably against MDR-MTB. This implies that pure compounds of these plants have the capability of reducing the doses and duration of treatment when combined with conventional anti-TB drugs. This may result in a multitude of advantages, ranging from preventing the emergence of resistance, increased compliancy and general reduction in global tuberculosis burden.