Antimycobacterial activity of Citrullus colocynthis (L.) Schrad. against drug sensitive and drug resistant Mycobacterium tuberculosis and MOTT clinical isolates

•The study provides scientific rationale for the traditional use of Citrullus colocynthis in the treatment of tuberculosis in India.•Ursolic acid, cucurbitacin E 2-0-β-d-glucopyranoside and cucurbitacin I 2-0-β-d-glucopyranoside were isolated from Citrullus colocynthis.•The isolated compounds showed activity against drug sensitive, drug resistant, MDR and XDR Mycobacterium tuberculosis and two MOTT clinical isolates.•Bioactive fractions showed better antitubercular activity than the isolated compounds which may be due to the synergistic effect of the other constituents.

Ethnopharmacological relevanceCitrullus colocynthis (Cucurbitaceae), a folk herbal medicine and traditionally used natural remedy for tuberculosis in India has been studied to validate its antitubercular activity against drug sensitive and drug resistant (including multidrug resistant) Mycobacterium tuberculosis and Mycobacterium other than tuberculosis (MOTT) bacilli.Materials and methodsInhibitory and bactericidal activities of crude extracts, fractions and compounds of Citrullus colocynthis plant, consisting of aerial parts and ripe deseeded fruits were performed against the drug sensitive standard strain of Mycobacterium tuberculosis H37Rv (ATCC 27294), 16 drug resistant strains of Mycobacterium tuberculosis and two MOTT strains, using radiometric BACTEC 460TB system.ResultsMethanolic extract of ripe deseeded fruit of Citrullus colocynthis has shown good activity (MIC≤62.5 µg/ml), whereas among the bioactive fractions, FC IX demonstrated the best activity (MIC 31.2 µg/ml) against Mycobacterium tuberculosis H37Rv. Bioactive FC III, IX and X also inhibited 16 clinical isolates of Mycobacterium tuberculosis consisting of seven non-multidrug resistants, eight multidrug resistants, one extensively drug resistant and two of MOTTs with MICs in the range of 50-125, 31.2-125 and 62.5-125 µg/ml, respectively. Ursolic acid and cucurbitacin E 2-0-β-d-glucopyranoside were identified as the main biomarkers active against Mycobacterium tuberculosis H37Rv (MICs 50 and 25 µg/ml respectively), as well as against the 18 clinical isolates. FC III and FC IX showed better inhibition of drug resistant and MOTT clinical isolates. Minimal bactericidal concentrations of extracts, fractions and compound C-2 were ≥two-fold MIC values.ConclusionsThe study provides a scientific rationale for the traditional use of Citrullus colocynthis fruit in the treatment of tuberculosis. In addition, the study elucidates a broad spectrum antimycobacterial action of Citrullus colocynthis fruit, which can contribute to the development of improved preparation of an antitubercular natural drug for the treatment of drug resistant tuberculosis and MOTT infection as well.

Graphical abstractDownload high-res image (127KB)Download full-size image