Ursolic and oleanolic acids as antimicrobial and immunomodulatory compounds for tuberculosis treatment

BMC Complementary and Alternative Medicine

Rogelio Hernández-Pando¹  Javier Torres⁴  Brenda Marquina¹  Dulce Mata-Espinosa¹  Mariana Meckes-Fischer³  María Eugenia Castro-Mussot²  Sonia López-García²  Jorge Cornejo-Garrido³  Julieta Luna-Herrera²  Adelina Jiménez-Arellanes³ 

[1]Sección de Patología Experimental, Departamento de Patología, Instituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán”, Secretaría de Salud, Vasco de Quiroga 15, Col. Sección XVI, Tlalpan 14000 D.F, México

[2]Laboratorio de Inmunoquímica II, Depto. Inmunología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, México 11340 D.F, México

[3]Unidad de Investigación Médica en Farmacología, Hospital de Especialidades, CMN Siglo XXI, IMSS, Ave Cuauhtémoc 330, Col. Doctores, México 06720 D.F, México

[4]Unidad de Investigación Médica en Enfermedades Infecciosas y Parasitarias, Hospital de Pediatría, CMN Siglo XXI, IMSS, Ave Cuauhtémoc 330, Col. Doctores, México 06720 D.F, México

关键词: Medicinal plants;    Antimycobacterial activity;    Antitubercular activity;    Triterpenoids;   

Others  :  1220902
DOI  :  10.1186/1472-6882-13-258

 received in 2013-02-21, accepted in 2013-09-24,  发布年份 2013

【 摘 要 】

Background

New alternatives for the treatment of Tuberculosis (TB) are urgently needed and medicinal plants represent a potential option. Chamaedora tepejilote and Lantana hispida are medicinal plants from Mexico and their hexanic extracts have shown antimycobacterial activity. Bioguided investigation of these extracts showed that the active compounds were ursolic acid (UA) and oleanolic acid (OA).

Methods

The activity of UA and OA against Mycobacterium tuberculosis H37Rv, four monoresistant strains, and two drug-resistant clinical isolates were determined by MABA test. The intracellular activity of UA and OA against M. tuberculosis H37Rv and a MDR clinical isolate were evaluated in a macrophage cell line. Finally, the antitubercular activity of UA and OA was tested in BALB/c mice infected with M. tuberculosis H37Rv or a MDR strain, by determining pulmonary bacilli loads, tissue damage by automated histomorphometry, and expression of IFN-γ, TNF-α, and iNOS by quantitative RT-PCR.

Results

The in vitro assay showed that the UA/OA mixture has synergistic activity. The intracellular activity of these compounds against M. tuberculosis H37Rv and a MDR clinical isolate in a macrophage cell line showed that both compounds, alone and in combination, were active against intracellular mycobacteria even at low doses. Moreover, when both compounds were used to treat BALB/c mice with TB induced by H37Rv or MDR bacilli, a significant reduction of bacterial loads and pneumonia were observed compared to the control. Interestingly, animals treated with UA and OA showed a higher expression of IFN-γ and TNF-α in their lungs, than control animals.

Conclusion

UA and OA showed antimicrobial activity plus an immune-stimulatory effect that permitted the control of experimental pulmonary TB.

【 授权许可】

   
2013 Jiménez-Arellanes et al.; licensee BioMed Central Ltd.

【 图 表 】

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