Safety evaluation and bioassay-guided isolation of antimycobacterial compounds from Morella salicifolia root ethanolic extract.

ETHNOPHARMACOLOGICAL RELEVANCE: Although the available medicines can cure almost all tuberculosis drug-susceptible patients some problems including the emergence of multi-drug resistant and extensively drug-resistant strains press for the need of new anti-TB medicines. Morella salicifolia is a common plant that is widely used in traditional medicine for managing HIV and AIDS-related conditions including tuberculosis but no studies have been done to evaluate its safety and efficacy. AIM OF THE STUDY: This study was designed to investigate the antimycobacterial activity and safety of M. salicifolia extract and its constituents. MATERIAL AND METHODS: Antimycobacterial activity of the crude extract was tested against non-pathogenic mycobacteria including Mycobacterium aurum (MA), Mycobacterium indicus pranii (MIP) and Mycobacterium madagascariense (MM) using the broth microdilution method. Bioassay-guided fractionation was employed to isolate the active compounds. Some of the isolated active compounds were tested for antimycobacterial activity against the standard and selected clinical isolates of M. tuberculosis. Safety of the crude extract was assessed using cytotoxicity assay and oral acute toxicity testing. RESULTS: The crude extract exhibited antimycobacterial activity against all the species used. The study led to isolation of six compounds; four pentacyclic triterpenoids; (3ß)-3-Hydroxyolean-12-en-28-oic acid (Oleanolic acid) (1), (2α,3ß)-2,3-Dihydroxyolean-12-en-28-oic acid (maslinic acid) (2), D-Friedoolean-14-ene-3ß,28-diol (taraxerol) (3), and D-Friedoolean-14-en-3ß-ol (myricadiol) (4), and two diarylheptanoids; (±)-myricanol (5) and myricanone (6). The six compounds exhibited activity against three nonpathogenic mycobacteria species. Compound 2, was the most active, with MICs of 17, 28 and 56 µg/ml against MM, standard a M. tuberculosis strain H37RV and rifampicin resistant M. tuberculosis clinical isolates, respectively. The crude extract did not show toxicity on peripheral blood mononuclear cells and it was safe in mice following acute oral toxicity test. CONCLUSION: The results from this study indicate that some isolated compounds in Morella salicifolia could form potential scaffolds for drug development efforts targeting M. tuberculosis. More studies are needed to further explore the potential of the plant extract and its secondary metabolites in the management of HIV and AIDS-related conditions using in-vivo models.

An Annotated Inventory of Tanzanian Medicinal Plants Traditionally Used for the Treatment of Respiratory Bacterial Infections.

This review comprehensively covers and analyzes scientific information on plants used in Tanzanian traditional medicine against respiratory diseases. It covers ethnobotanical and ethnopharmacological information extracted from SciFinder, Google Scholar, and Reaxys as well as the literature collected at the Institute of Traditional Medicine in Dar-es-Salaam. Crude extracts and fractions of 133 plant species have literature reports on antimicrobial bioassays. Of these, 16 plant species had a minimum inhibitory activity of MIC ≤ 50 µg/mL. Structurally diverse compounds were reported for 49 plant species, of which 7 had constituents with MIC ≤ 5 µg/mL against various bacteria: Bryophyllum pinnatum (Lam.) Oken, Warburgia ugandensis Sprague, Diospyros mespiliformis Hochst. ex DC., Cassia abbreviata Oliv., Entada abyssinica A. Rich., Strychnos spinosa Lam., and Milicia excelsa (Welw.) C.C. Berg. The low number of antimicrobial active extracts and compounds suggests that antibacterial and antimycobacterial drug discovery needs to have a fresh look at ethnobotanical information, diverting from too reductionist an approach and better taking into account that the descriptions of symptoms and concepts of underlying diseases are different in traditional African and modern Western medicine. Nevertheless, some structurally diverse compounds found in anti-infective plants are highlighted in this review as worthy of detailed study and chemical modification.