In vitro effect of ursolic acid on the inhibition of Mycobacterium tuberculosis and its cell wall mycolic acid.

Mycobacterium tuberculosis is a dangerous intracellular pathogen. In order to protect against mycobacterium infection, novel agents with anti-mycobacterial activity should be given emergency priority for evaluation. Ursolic acid (UA), a plant triterpenoid, shows promising bioactivities, including anti-mycobacterial potency. In this study, the action of UA against Mycobacterium tuberculosis H37Ra was evaluated, and the inhibitory concentration was found to range between 10 and 20 μg/ml in a resazurin assay and MGIT 960 instrument. The total mycolic acid in UA-treated H37Ra was detected and compared with INH-treated and non-treated bacterium by LC-MS/MS. Quantitative LC-MS/MS data confirmed that both UA and INH decreased mycolic acid biosynthesis in a dose-dependent manner. Thin-layer chromatogram (TLC) analysis showed that all mycolic acid subtypes were affected by UA treatment in the wild type but not in strains resistant to UA. Electron microscopy images also confirmed that UA treatment affected both H37Ra cell and intracellular content of H37Ra. Altogether, these data confirmed the promise of the inhibitory action of UA in mycolic acid, which might further delineate the mechanistic pathway of mycobacterial inhibition by UA.