Ursolic and oleanolic acids as antimicrobial and immunomodulatory compounds for tuberculosis treatment View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2013-10-07

AUTHORS

Adelina Jiménez-Arellanes, Julieta Luna-Herrera, Jorge Cornejo-Garrido, Sonia López-García, María Eugenia Castro-Mussot, Mariana Meckes-Fischer, Dulce Mata-Espinosa, Brenda Marquina, Javier Torres, Rogelio Hernández-Pando

ABSTRACT

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. More... »

PAGES

258-258

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/1472-6882-13-258

DOI

http://dx.doi.org/10.1186/1472-6882-13-258

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1047117525

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/24098949


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25 schema:description 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.
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34 Chamaedora tepejilote
35 H37Rv
36 IFN
37 Lantana hispida
38 MABA test
39 MDR bacilli
40 MDR clinical isolates
41 MDR strains
42 Mexico
43 Mycobacterium tuberculosis H37Rv
44 OA mixture
45 RT-PCR
46 TNF
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48 acid
49 active compounds
50 activity
51 activity of UA
52 alternative
53 animals
54 antimicrobial activity
55 antimycobacterial activity
56 antitubercular activity
57 bacilli
58 bacilli load
59 bacterial load
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65 control
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78 histomorphometry
79 iNOS
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81 immunomodulatory compounds
82 intracellular activity
83 intracellular mycobacteria
84 investigation
85 isolates
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87 load
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89 lung
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91 medicinal plants
92 mice
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94 monoresistant strains
95 mycobacteria
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97 oleanolic acid
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102 pulmonary TB
103 pulmonary bacilli loads
104 quantitative RT-PCR
105 reduction
106 significant reduction
107 strains
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109 tepejilote
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