Evaluation of antimycobacterial activity of Zanthoxylum leprieurii guill. & Perr. and Rubia cordifolia l and their interaction with conventional anti- tuberculosis drugs used for the treatment of tuberculosis in Uganda

Abstract

Background: Tuberculosis (TB) remains a public health challenge and one of the leading causes of death worldwide. TB is preventable and curable. However, treatment of tuberculosis has continued to be difficult as a result of rapid emergence of multidrug resistant (MDR) and extensively drug resistant (XDR) strains of Mycobacterium tuberculosis (MTB). Medicinal plants have for centuries been traditionally used in treatment Of tuberculosis and similar ailments globally. They possess antimicrobial properties which render them a new hope as a source of novel bioactive leads in the development of antimycobacterial agents. Additionally, despite the increasing acceptance of medicinal plant use in combination with conventional antituberculosis drugs in treatment Of tuberculosis (TB) in Uganda, there is paucity or knowledge On their combination effect. Methods: Two plant species commonly used traditionally for the treatment Of tuberculosis in Uganda, Zanthoxylum leprieurii Guill- & perr. and Rubia cordifolia L. were screened for in vitro antimycobacterial activity against Mycobacterium tuberculosis strains; pan sensitive MTB H37Rv, Rifampicin resistant TMC 331 strain and two wild strains (one rifampicin resistant and another one rifampicin susceptible). Antimycobacterial activity of aqueous, ethanolic and methanolic plant extracts was determined using Resazurin Microtiter Assay (REMA). We also determined the combination activity of both medicinal plant extracts at varying concentrations and standard antituberculosis drugs against H37Rv and MDR (TMC 331) strains. cytotoxic effect of the active plant extracts was determined against the mouse BALB/C monocyte-macrophage (J774.2) cells using Microculture Tetrazolium (MIT) assay. Results: Both plant extracts exhibited significant in vitro antimycobacterial activity against all MTB strains. Minimum inhibitory concentrations (MIC) of methanolic crude extracts of both plants ranged from 23.4gg/mL to 187.5gg/mL. Comparatively, methanol extracts of both plants possessed superior antimycobacterial activity against all the strains. Drug-extract combinations showed good combination activity against Mycobacterium tuberculosis Strains when compared with individual Standard anti-TB drugs especially against MDR-MTB strain. All extracts exhibited moderate to weak cytotoxicity against J774.2 mouse macrophage monocyte cell line in a dose dependent manner. Conclusions: Our findings indicated that both plants exhibited activity against susceptible and resistant strains Of Mycobacterium tuberculosis. While antimycobacterial activity Of Z leprieurii confirms results from previous studies, activity of the extracts Of R. cordifolia is reported for the first time in East Africa. Zanthoxylum leprieurii and Rubia cordifolia in combination with standard anti-TB drugs exhibited increased in vitro activity against Mycobacterium tuberculosis especially MI)R-MTB strain. This verifies the local use of these plants in traditional treatment of tuberculosis in Uganda.