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 mc²155 and Mycobacterium bovis BCG, and therefore a bioassay-guided isolation strategy was undertaken. (Z)-Ligustilide, (Z)-3-butylidenephthalide, (E)-3-butylidenephthalide, 3-butylphthalide, α-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 H₃₇Rv 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 H₃₇Rv strain; however, it was found to be cytotoxic with a half-growth inhibitory concentration (GIC₅₀) in the same order of magnitude (SI < 1). Interestingly the sesquiterpene alcohol α-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 ~ 2). Colony forming unit analysis at different concentrations of this phytochemical showed mycobacteriostatic mode of action.
Mycobacteria Research Laboratory, Department of Biological Sciences, Institute of Structural and Molecular Biology, Birkbeck, University of London, Malet Street, London WC1E 7HX, UK.
Juan David
JD
Guzman
Dimitrios
D
Evangelopoulos
Antima
A
Gupta
Jose M
JM
Prieto
Simon
S
Gibbons
Sanjib
S
Bhakta
D015107:4-Butyrolactone / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000904:Antibiotics, Antitubercular / Q000302:isolation & purification / Q000494:pharmacology*; D003603:Cytotoxins / Q000737:chemistry / Q000494:pharmacology*; D053280:Diynes / Q000494:pharmacology / Q000627:therapeutic use; D005233:Fatty Alcohols / Q000494:pharmacology / Q000627:therapeutic use; D011564:Furocoumarins / Q000494:pharmacology / Q000627:therapeutic use; D030004:Ligusticum / Q000737:chemistry*; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D009163:Mycobacterium bovis / Q000187:drug effects*; D020102:Mycobacterium smegmatis / Q000187:drug effects*; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology*; D018517:Plant Roots / Q000737:chemistry; D012717:Sesquiterpenes / Q000494:pharmacology / Q000627:therapeutic use
D000904:Antibiotics, Antitubercular; D003603:Cytotoxins; D053280:Diynes; D005233:Fatty Alcohols; D011564:Furocoumarins; D010936:Plant Extracts; D012717:Sesquiterpenes; C027820:ligustilide; C034379:falcarindiol; D015107:4-Butyrolactone