Reports have shown that oleanolic acid (OA), a triterpenoid, exists widely in food, medicinal herbs and other plants, and that it has antimycobacterial activity against the Mycobacterium tuberculosis strain H37Rv (ATCC 27294). In this study it was found that OA had antimycobacterial properties against eight clinical isolates of M. tuberculosis and that the MICs of OA against drug-sensitive and drug-resistant isolates were 50–100 and 100–200 μg ml−1, respectively. The combination of OA with isoniazid (INH), rifampicin (RMP) or ethambutol (EMB) showed favourable synergistic antimycobacterial effects against six drug-resistant strains, with fractional inhibitory concentration indices of 0.121–0.347, 0.113–0.168 and 0.093–0.266, respectively. The combination treatments of OA/INH, OA/RMP and OA/EMB displayed either a synergistic interaction or did not show any interaction against two drug-sensitive strains. No antagonism resulting from the OA/INH, OA/RMP or OA/EMB combination was observed for any of the strains tested. OA exhibited a relatively low cytotoxicity in Vero cells. These results indicate that OA may serve as a promising lead compound for future antimycobacterial drug development.
BamuambaK.,
GammonD. W.,
MeyersP.,
Dijoux-FrancaM. G.,
ScottG.2008; Anti-mycobacterial activity of five plant species used as traditional medicines in the Western Cape Province (South Africa). J Ethnopharmacol 117:385–390[CrossRef]
BannoN.,
AkihisaT.,
TokudaH.,
YasukawaK.,
HigashiharaH.,
UkiyaM.,
WatanabeK.,
KimuraY.,
HasegawaJ.,
NishinoH.2004; Triterpene acids from the leaves of Perilla frutescens and their anti-inflammatory and antitumor-promoting effects. Biosci Biotechnol Biochem 68:85–90[CrossRef]
De LoguA.,
OnnisV.,
SaddiB.,
CongiuC.,
SchivoM. L.,
CoccoM. T.2002; Activity of a new class of isonicotinoylhydrazones used alone and in combination with isoniazid, rifampicin, ethambutol, para-aminosalicylic acid and clofazimine against Mycobacterium tuberculosis
. J Antimicrob Chemother 49:275–282[CrossRef]
De LoguA.,
SaddiM.,
OnnisV.,
SannaC.,
CongiuC.,
BorgnaR.,
CoccoM. T.2005; In vitro antimycobacterial activity of newly synthesised S -alkylisothiosemicarbazone derivatives and synergistic interactions in combination with rifamycins against Mycobacterium avium
. Int J Antimicrob Agents 26:28–32[CrossRef]
GuJ. Q.,
WangY.,
FranzblauS. G.,
MontenegroG.,
TimmermannB. N.2004; Constituents of Quinchamalium majus with potential antitubercular activity. Z Naturforsch C 59:797–802
KentR. J.,
BakhtiarM.,
ShansonD. C.1992; The in-vitro bactericidal activities of combinations of antimicrobial agents against clinical isolates of Mycobacterium avium-intracellulare
. J Antimicrob Chemother 30:643–650[CrossRef]
MosmannT.1983; Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 65:55–63[CrossRef]
StrattonC. W.,
CookseyR. C.1991; Susceptibility tests: special tests. In The Manual of Clinical Microbiology , 5th edn. pp 1153–1165 Edited by
BalowsA.,
HauslerW. J.Jr,
HermannK. L.,
IsenbergH. D.,
ShadomyH. J.
Washington, DC: American Society for Microbiology;
YoonY. H.,
JungK. H.,
SadunA. A.,
ShinH. C.,
KohJ. Y.2000; Ethambutol-induced vacuolar changes and neuronal loss in rat retinal cell culture: mediation by endogenous zinc. Toxicol Appl Pharmacol 162:107–114[CrossRef]