Antimycobacterials from Lovage Root (Ligusticum officinale Koch)

The n-hexane extract of Lovage root was found to significantly inhibit the growth of both Mycobacterium smegmatis mc(2)155 and Mycobacterium bovis BCG, and therefore a bioassay-guided isolation strategy was undertaken. (Z)-Ligustilide, (Z)-3-butylidenephthalide, (E)-3-butylidenephthalide, 3-butylphthalide, -prethapsenol, falcarindiol, levistolide A, psoralen and bergapten were isolated by chromatographic techniques, characterized by NMR spectroscopy and MS, and evaluated for their growth inhibition activity against Mycobacterium tuberculosis H(37)Rv using the whole-cell phenotypic spot culture growth inhibition assay (SPOTi). Cytotoxicity against RAW 264.7 murine macrophage cells was employed for assessing their degree of selectivity. Falcarindiol was the most potent compound with a minimum inhibitory concentration (MIC) value of 20 mg/L against the virulent H(37)Rv strain; however, it was found to be cytotoxic with a half-growth inhibitory concentration (GIC(50)) in the same order of magnitude (SI<1). Interestingly the sesquiterpene alcohol -prethapsenol was found to inhibit the growth of the pathogenic mycobacteria with an MIC value of 60 mg/L, being more specific towards mycobacteria than mammalian cells (SI similar to 2). Colony forming unit analysis at different concentrations of this phytochemical showed mycobacteriostatic mode of action. Copyright (c) 2012 John Wiley & Sons, Ltd.