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 drugsusceptible patients some problems including the emergence of multi-drug resistant and extensively drugresistant 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; (38)-3-Hydroxyolean-12-en-28-oic acid (Oleanolic acid) (1), (2a,38)-2,3-Dihydroxyolean-12-en-28-oic acid (maslinic acid) (2), D-Friedoolean-14-ene-38,28-diol (taraxerol) (3), and D-Friedoolean-14-en-38-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 mu g/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 AIDSrelated conditions using in-vivo models.

Automated summary

The extract of Morella salicifolia exhibited antimycobacterial activity against different mycobacteria species, and the isolated compounds showed potential for drug development targeting M. tuberculosis. The most active compound, maslinic acid, displayed activity against rifampicin-resistant clinical isolates. Additionally, the crude extract showed good safety profile in vitro and in vivo.