In vitro synergistic interactions of oleanolic acid in combination with isoniazid, rifampicin or ethambutol against Mycobacterium tuberculosis.
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 microg 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.
Ge
Fa
F
Key Laboratory of Zoonosis, Ministry of Education, Institute of Zoonosis, College of Animal Science and Veterinary Medicine, Jilin University, Changchun 130062, PR China.
Zeng
Fanli
F
Department of Animal Science Technology, Jilin Agricultural University, Changchun 130118, PR China.
Liu
Siguo
S
Division of Bacterial Diseases, Harbin Veterinary Research Institute, Harbin 150001, PR China.
Guo
Na
N
Laboratory of Nutrition and Functional Food, Jilin University, Changchun 130062, PR China.
Ye
Haiqing
H
Laboratory of Nutrition and Functional Food, Jilin University, Changchun 130062, PR China.
Song
Yu
Y
Key Laboratory of Zoonosis, Ministry of Education, Institute of Zoonosis, College of Animal Science and Veterinary Medicine, Jilin University, Changchun 130062, PR China.
Fan
Junwen
J
Laboratory Animal Center, Academy of Military Medical Sciences, Beijing 100071, PR China.
Wu
Xiuping
X
Key Laboratory of Zoonosis, Ministry of Education, Institute of Zoonosis, College of Animal Science and Veterinary Medicine, Jilin University, Changchun 130062, PR China.
Wang
Xuelin
X
Key Laboratory of Zoonosis, Ministry of Education, Institute of Zoonosis, College of Animal Science and Veterinary Medicine, Jilin University, Changchun 130062, PR China.
Deng
Xuming
X
Key Laboratory of Zoonosis, Ministry of Education, Institute of Zoonosis, College of Animal Science and Veterinary Medicine, Jilin University, Changchun 130062, PR China.
Jin
Qi
Q
Institute of Pathogen Biology, Chinese Academy of Medical Sciences, Beijing 100730, PR China.
Yu
Lu
L
Key Laboratory of Zoonosis, Ministry of Education, Institute of Zoonosis, College of Animal Science and Veterinary Medicine, Jilin University, Changchun 130062, PR China.
D000995:Antitubercular Agents / Q000494:pharmacology*; D004357:Drug Synergism; D004977:Ethambutol / Q000494:pharmacology*; D006801:Humans; D007538:Isoniazid / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000302:isolation & purification; D009828:Oleanolic Acid / Q000494:pharmacology*; D012293:Rifampin / Q000494:pharmacology*; D014376:Tuberculosis / Q000382:microbiology
D000995:Antitubercular Agents; D009828:Oleanolic Acid; D004977:Ethambutol; D007538:Isoniazid; D012293:Rifampin