In vitro antimycobacterial activity of medicinal plants Lantana camara, Cryptolepis sanguinolenta, and Zanthoxylum leprieurii.

Background: Imperative need exists to search for new anti-TB drugs that are safer, and more effective against drug-resistant strains. Medicinal plants have been the source of active ingredients for drug development. However, the slow growth and biosafety level requirements of M. tuberculosis culture are considerable challenges. M. smegmatis can be used as a surrogate for M. tuberculosis. In the current study, preliminary phytochemical screening and antimycobacterial activity evaluation of crude methanolic extracts of medicinal plants against M. smegmatis, and two M. tuberculosis strains, were conducted. Materials and Methods: Crude methanolic extracts, obtained from the leaves of L. camara, roots of C. sanguinolenta, and stem barks of Z. leprieurii, were tested for antimycobacterial activity against M. smegmatis (mc2155), pan-sensitive (H37Rv), and rifampicin-resistant (TMC-331) M. tuberculosis, using visual Resazurin Microtiter Assay (REMA) on 96 well plates. Preliminary qualitative phytochemical screening tests were performed using standard chemical methods. Results: The three methanolic extracts inhibited mycobacterial growth in vitro. They were more active against rifampicin-resistant strain with MICs of 176, 97, and 45 µg/mL for L. camara, C. sanguinolenta, and Z. leprieurii extracts, respectively. The lowest activity was observed against M. smegmatis with MICs of 574, 325, and 520 µg/mL, respectively. Against H37Rv, activity was intermediate to those of TMC-331 and mc2155. However, L. camara extract showed the same activity against H37Rv and M. smegmatis. Preliminary phytochemical analysis revealed alkaloids, flavonoids, phenolic compounds, saponins, tannins, and terpenoids. Conclusions: Leaves of L. camara, roots of C. sanguinolenta, and stem barks of Z. leprieurii exhibit antimycobacterial activity against M. smegmatis, pan-sensitive, and rifampicin-resistant M. tuberculosis. This offers the possibilities for novel therapeutic opportunities against TB including multidrug-resistant TB. Further investigations on safety and mechanisms of action are required. These studies could be done using M. smegmatis as a surrogate for the highly pathogenic M. tuberculosis.

Three promising antimycobacterial medicinal plants reviewed as potential sources of drug hit candidates against multidrug-resistant tuberculosis.

Regimens of current drugs for tuberculosis are lengthy and are associated with many adverse effects. Currently, the emergence of different resistant strains has been observed. This urges a need for the discovery and development of novel drugs. The main sources of drug lead candidates are based on natural products. Zanthoxylum leprieurii, Lantana camara, and Cryptolepis Sanguinolenta are among the plants that have antimycobacterial activity. Recent technological methods, such as metabolomics, can rapidly detect and identify active compounds from medicinal plants. In this review, we aim to provide an overview and discussion of the antimycobacterial activity, phytochemical analysis and toxicity profile of these plants and their products as well as the potential of metabolomic fingerprinting of medicinal plants with a given activity on microbes, in the search for the potential drug hit molecules. The information for this review was extracted from databases such as Excerpta Medica Database, Google Scholar, Springer, and PubMed Central. Primary studies, using a combination of the keywords antimycobacterial medicinal plant, multidrug-resistant tuberculosis, phytochemistry, toxicity, Zanthoxylum leprieurii, Lantana camara, Cryptolepis sanguinolenta, and plant metabolomics/metabolic fingerprinting of plant extracts, have been considered. The above-mentioned plant species showed antimycobacterial activity against drug-resistant strains of M. tuberculosis. They may provide potential candidates for novel drugs against multidrug-resistant tuberculosis. However, extensive work is still needed. To our knowledge, there is no or limited literature that reports the metabolic fingerprints of these plants. The analysis of the metabolite fingerprints of medicinal plants with similar antimicrobial activity could be important to determine whether the activity results from common metabolites within different plant species. This review shows that these plants are potential candidates to provide drug hits against multidrug-resistant tuberculosis strains. Future studies of compound optimization, in vivo safety and efficacy, as well as of the specific mechanisms of action are however required.

Application of metabolomics to drug discovery and understanding the mechanisms of action of medicinal plants with anti-tuberculosis activity.

Human tuberculosis (TB) is amongst the oldest and deadliest human bacterial diseases that pose major health, social and economic burden at a global level. Current regimens for TB treatment are lengthy, expensive and ineffective to emerging drug resistant strains. Thus, there is an urgent need for identification and development of novel TB drugs and drug regimens with comprehensive and specific mechanisms of action. Many medicinal plants are traditionally used for TB treatment. While some of their phytochemical composition has been elucidated, their mechanisms of action are not well understood. Insufficient knowledge on Mycobacterium tuberculosis (M.tb) biology and the complex nature of its infection limit the effectiveness of current screening-based methods used for TB drug discovery. Nonetheless, application of metabolomics tools within the 'omics' approaches, could provide an alternative method of elucidating the mechanism of action of medicinal plants. Metabolomics aims at high throughput detection, quantification and identification of metabolites in biological samples. Changes in the concentration of specific metabolites in a biological sample indicate changes in the metabolic pathways. In this paper review and discuss novel methods that involve application of metabolomics to drug discovery and the understanding of mechanisms of action of medicinal plants with anti-TB activity. Current knowledge on TB infection, anti-TB drugs and mechanisms of action are also included. We further highlight metabolism of M. tuberculosis and the potential drug targets, as well as current approaches in the development of anti-TB drugs.