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The cytotoxic effects of brown Cuban propolis depend on the nemorosone content and may be mediated by mitochondrial uncoupling.

Abstract

Three main types of Cuban propolis directly related to their secondary metabolite composition have been identified: brown, red and yellow propolis; the former is majoritarian and is characterized by the presence of nemorosone. In this study, brown Cuban propolis extracts were found cytotoxic against HepG2 cells and primary rat hepatocytes, in close association with the nemorosone contents. In mitochondria isolated from rat liver the extracts displayed uncoupling activity, which was demonstrated by the increase in succinate-supported state 4 respiration rates, dissipation of mitochondrial membrane potential, Ca(2+) release from Ca(2+)-loaded mitochondria, and a marked ATP depletion. As in cells, the degree of such mitotoxic events was closely correlated to the nemorosone content. The propolis extracts that do not contain nemorosone were neither cytotoxic nor mitotoxic, except R-29, whose detrimental effect upon cells and mitochondria could be mediated by its isoflavonoids and chalcones components, well known mitochondrial uncouplers. Our results at least partly unravel the cytotoxic mechanism of Cuban propolis, particularly regarding brown propolis, and raise concerns about the toxicological implication of Cuban propolis consumption.

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  • Authors+Show Affiliations

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    Centro de Estudio para las Investigaciones y Evaluaciones Biológicas, Instituto de Farmacia y Alimentos de La Universidad de La Habana, La Habana, Cuba. Electronic address: gpardo@ifal.uh.cu.

    ,

    Departamento de Física e Química, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil.

    ,

    Departamento de Física e Química, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil.

    ,

    Centro para las Investigaciones y Desarrollo de Medicamentos, Ciudad Habana, Cuba.

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    Centro de Estudio para las Investigaciones y Evaluaciones Biológicas, Instituto de Farmacia y Alimentos de La Universidad de La Habana, La Habana, Cuba.

    ,

    Departamento de Analises Clinicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil; Núcleo de Pesquisas em Produtos Naturais e Sintéticos (NPPNS), Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil.

    ,

    Departamento de Física e Química, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil; Núcleo de Pesquisas em Produtos Naturais e Sintéticos (NPPNS), Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil.

    Departamento de Física e Química, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil; Núcleo de Pesquisas em Produtos Naturais e Sintéticos (NPPNS), Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil.

    Source

    Chemico-biological interactions 228: 2015 Feb 25 pg 28-34

    MeSH

    Animals
    Benzophenones
    Calcium
    Cell Survival
    Cuba
    Dose-Response Relationship, Drug
    Hep G2 Cells
    Hepatocytes
    Humans
    Membrane Potential, Mitochondrial
    Mitochondria, Liver
    Plant Extracts
    Propolis
    Rats
    Structure-Activity Relationship
    Uncoupling Agents

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    25617483

    Citation

    Pardo Andreu, Gilberto L., et al. "The Cytotoxic Effects of Brown Cuban Propolis Depend On the Nemorosone Content and May Be Mediated By Mitochondrial Uncoupling." Chemico-biological Interactions, vol. 228, 2015, pp. 28-34.
    Pardo Andreu GL, Reis FH, Dalalio FM, et al. The cytotoxic effects of brown Cuban propolis depend on the nemorosone content and may be mediated by mitochondrial uncoupling. Chem Biol Interact. 2015;228:28-34.
    Pardo Andreu, G. L., Reis, F. H., Dalalio, F. M., Nuñez Figueredo, Y., Cuesta Rubio, O., Uyemura, S. A., ... Alberici, L. C. (2015). The cytotoxic effects of brown Cuban propolis depend on the nemorosone content and may be mediated by mitochondrial uncoupling. Chemico-biological Interactions, 228, pp. 28-34. doi:10.1016/j.cbi.2015.01.010.
    Pardo Andreu GL, et al. The Cytotoxic Effects of Brown Cuban Propolis Depend On the Nemorosone Content and May Be Mediated By Mitochondrial Uncoupling. Chem Biol Interact. 2015 Feb 25;228:28-34. PubMed PMID: 25617483.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - The cytotoxic effects of brown Cuban propolis depend on the nemorosone content and may be mediated by mitochondrial uncoupling. AU - Pardo Andreu,Gilberto L, AU - Reis,Felippe H Z, AU - Dalalio,Felipe M, AU - Nuñez Figueredo,Yanier, AU - Cuesta Rubio,Osmany, AU - Uyemura,Sergio A, AU - Curti,Carlos, AU - Alberici,Luciane C, Y1 - 2015/01/21/ PY - 2014/10/19/received PY - 2014/12/28/revised PY - 2015/01/07/accepted PY - 2015/1/25/entrez PY - 2015/1/27/pubmed PY - 2015/4/23/medline KW - Cuban propolis KW - Cytotoxic KW - Mitochondria KW - Nemorosone KW - Toxicity KW - Uncoupling SP - 28 EP - 34 JF - Chemico-biological interactions JO - Chem. Biol. Interact. VL - 228 N2 - Three main types of Cuban propolis directly related to their secondary metabolite composition have been identified: brown, red and yellow propolis; the former is majoritarian and is characterized by the presence of nemorosone. In this study, brown Cuban propolis extracts were found cytotoxic against HepG2 cells and primary rat hepatocytes, in close association with the nemorosone contents. In mitochondria isolated from rat liver the extracts displayed uncoupling activity, which was demonstrated by the increase in succinate-supported state 4 respiration rates, dissipation of mitochondrial membrane potential, Ca(2+) release from Ca(2+)-loaded mitochondria, and a marked ATP depletion. As in cells, the degree of such mitotoxic events was closely correlated to the nemorosone content. The propolis extracts that do not contain nemorosone were neither cytotoxic nor mitotoxic, except R-29, whose detrimental effect upon cells and mitochondria could be mediated by its isoflavonoids and chalcones components, well known mitochondrial uncouplers. Our results at least partly unravel the cytotoxic mechanism of Cuban propolis, particularly regarding brown propolis, and raise concerns about the toxicological implication of Cuban propolis consumption. SN - 1872-7786 UR - https://www.unboundmedicine.com/medline/citation/25617483/The_cytotoxic_effects_of_brown_Cuban_propolis_depend_on_the_nemorosone_content_and_may_be_mediated_by_mitochondrial_uncoupling_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0009-2797(15)00016-2 DB - PRIME DP - Unbound Medicine ER -