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Evaluation of the anti-mycobacterium tuberculosis activity and in vivo acute toxicity of Annona sylvatic

BACKGROUND: The recent emergence of extensively multidrug-resistant Mycobacterium tuberculosis strains has further complicated the control of tuberculosis. There is an urgent need for the development of new molecular candidates antitubercular drugs. Medicinal plants have been an excellent source of...

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Autores principales: Araujo, Rafaele CP, Neves, Francisco AR, Formagio, Anelise SN, Kassuya, Candida AL, Stefanello, Maria EA, Souza, Vanessa V, Pavan, Fernando R, Croda, Julio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4082671/
https://www.ncbi.nlm.nih.gov/pubmed/24974069
http://dx.doi.org/10.1186/1472-6882-14-209
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author Araujo, Rafaele CP
Neves, Francisco AR
Formagio, Anelise SN
Kassuya, Candida AL
Stefanello, Maria EA
Souza, Vanessa V
Pavan, Fernando R
Croda, Julio
author_facet Araujo, Rafaele CP
Neves, Francisco AR
Formagio, Anelise SN
Kassuya, Candida AL
Stefanello, Maria EA
Souza, Vanessa V
Pavan, Fernando R
Croda, Julio
author_sort Araujo, Rafaele CP
collection PubMed
description BACKGROUND: The recent emergence of extensively multidrug-resistant Mycobacterium tuberculosis strains has further complicated the control of tuberculosis. There is an urgent need for the development of new molecular candidates antitubercular drugs. Medicinal plants have been an excellent source of leads for the development of drugs. The aim of this study was to evaluate the in vitro activity of 28 alcoholic extracts and essential oils of native and exotic Brazilian plants against Mycobacterium tuberculosis and to further study these extracts through chemical fractionation, the isolation of their constituents, and an evaluation of the in vivo acute toxicity of the active extracts. To the best of our knowledge this is the first chemical characterization, antituberculosis activity and acute toxicity evaluation of Annona sylvatica. METHODS: The anti-mycobacterial activity of these extracts and their constituent compounds was evaluated using the resazurin reduction microtiter assay (REMA). To investigate the acute toxicity of these extracts in vivo, female Swiss mice were treated with the extracts at doses of 500, 1000 and 2000 mg · kg(-1) of body weight. The extracts were characterized by LC-MS, and the constituents were isolated and identified by chromatographic analysis of spectroscopic data. RESULTS: Of the 28 extracts, the methanol extract obtained from the leaves of Annona sylvatica showed anti-mycobacterial activity with an minimal inhibitory concentration (MIC) of 184.33 μg/mL, and the ethyl acetate fraction (EAF) resulting from liquid-liquid partitioning of the A. sylvatica extract showed an MIC of 115.2 μg/mL. The characterization of this extract by LC-MS identified flavonoids and acetogenins as its main constituents. The phytochemical study of the A. sylvatica EAF resulted in the isolation of quercetin, luteolin, and almunequin. CONCLUSIONS: Among the compounds isolated from the EAF, luteolin and almunequin were the most promising, with MICs of 236.8 μg/mL (827.28 μM) and 209.9 μg/mL (328.48 μM), respectively. The acute administration of the EAF fraction in doses of 500, 1000, and 2000 mg · kg(-1) of body weight did not cause signs of toxicity in the treated animals.
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spelling pubmed-40826712014-07-06 Evaluation of the anti-mycobacterium tuberculosis activity and in vivo acute toxicity of Annona sylvatic Araujo, Rafaele CP Neves, Francisco AR Formagio, Anelise SN Kassuya, Candida AL Stefanello, Maria EA Souza, Vanessa V Pavan, Fernando R Croda, Julio BMC Complement Altern Med Research Article BACKGROUND: The recent emergence of extensively multidrug-resistant Mycobacterium tuberculosis strains has further complicated the control of tuberculosis. There is an urgent need for the development of new molecular candidates antitubercular drugs. Medicinal plants have been an excellent source of leads for the development of drugs. The aim of this study was to evaluate the in vitro activity of 28 alcoholic extracts and essential oils of native and exotic Brazilian plants against Mycobacterium tuberculosis and to further study these extracts through chemical fractionation, the isolation of their constituents, and an evaluation of the in vivo acute toxicity of the active extracts. To the best of our knowledge this is the first chemical characterization, antituberculosis activity and acute toxicity evaluation of Annona sylvatica. METHODS: The anti-mycobacterial activity of these extracts and their constituent compounds was evaluated using the resazurin reduction microtiter assay (REMA). To investigate the acute toxicity of these extracts in vivo, female Swiss mice were treated with the extracts at doses of 500, 1000 and 2000 mg · kg(-1) of body weight. The extracts were characterized by LC-MS, and the constituents were isolated and identified by chromatographic analysis of spectroscopic data. RESULTS: Of the 28 extracts, the methanol extract obtained from the leaves of Annona sylvatica showed anti-mycobacterial activity with an minimal inhibitory concentration (MIC) of 184.33 μg/mL, and the ethyl acetate fraction (EAF) resulting from liquid-liquid partitioning of the A. sylvatica extract showed an MIC of 115.2 μg/mL. The characterization of this extract by LC-MS identified flavonoids and acetogenins as its main constituents. The phytochemical study of the A. sylvatica EAF resulted in the isolation of quercetin, luteolin, and almunequin. CONCLUSIONS: Among the compounds isolated from the EAF, luteolin and almunequin were the most promising, with MICs of 236.8 μg/mL (827.28 μM) and 209.9 μg/mL (328.48 μM), respectively. The acute administration of the EAF fraction in doses of 500, 1000, and 2000 mg · kg(-1) of body weight did not cause signs of toxicity in the treated animals. BioMed Central 2014-06-28 /pmc/articles/PMC4082671/ /pubmed/24974069 http://dx.doi.org/10.1186/1472-6882-14-209 Text en Copyright © 2014 Araujo et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Araujo, Rafaele CP
Neves, Francisco AR
Formagio, Anelise SN
Kassuya, Candida AL
Stefanello, Maria EA
Souza, Vanessa V
Pavan, Fernando R
Croda, Julio
Evaluation of the anti-mycobacterium tuberculosis activity and in vivo acute toxicity of Annona sylvatic
title Evaluation of the anti-mycobacterium tuberculosis activity and in vivo acute toxicity of Annona sylvatic
title_full Evaluation of the anti-mycobacterium tuberculosis activity and in vivo acute toxicity of Annona sylvatic
title_fullStr Evaluation of the anti-mycobacterium tuberculosis activity and in vivo acute toxicity of Annona sylvatic
title_full_unstemmed Evaluation of the anti-mycobacterium tuberculosis activity and in vivo acute toxicity of Annona sylvatic
title_short Evaluation of the anti-mycobacterium tuberculosis activity and in vivo acute toxicity of Annona sylvatic
title_sort evaluation of the anti-mycobacterium tuberculosis activity and in vivo acute toxicity of annona sylvatic
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4082671/
https://www.ncbi.nlm.nih.gov/pubmed/24974069
http://dx.doi.org/10.1186/1472-6882-14-209
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