title: Vimang (Mangifera indica L. extract) induces permeability transition in isolated mitochondria, closely reproducing the effect of mangiferin, Vimang's main component.
abstract: Mitochondrial permeability transition (MPT) is a Ca(2+)-dependent, cyclosporin A (CsA)-sensitive, non-selective inner membrane permeabilization process. It is often associated with apoptotic cell death, and is induced by a wide range of agents or conditions, usually involving reactive oxygen species (ROS). In this study, we demonstrated that Mangifera indica L. extract (Vimang), in the presence of 20 microM Ca(2+), induces MPT in isolated rat liver mitochondria, assessed as CsA-sensitive mitochondrial swelling, closely reproducing the same effect of mangiferin, the main component of the extract, as well as MPT-linked processes like oxidation of membrane protein thiols, mitochondrial membrane potential dissipation and Ca(2+) release from organelles. The flavonoid catechin, the second main component of Vimang, also induces MPT, although to a lesser extent; the minor, but still representative Vimang extract components, gallic and benzoic acids, show respectively, low and high MPT inducing abilities. Nevertheless, following exposure to H(2)O(2)/horseradish peroxidase, the visible spectra of these compounds does not present the same changes previously reported for mangiferin. It is concluded that Vimang-induced MPT closely reproduces mangiferin effects, and proposed that this xanthone is the main agent responsible for the extract's MPT inducing ability, by the action on mitochondrial membrane protein thiols of products arising as a consequence of the mangiferin's antioxidant activity. While this effect would oppose the beneficial effect of Vimang's antioxidant activity, it could nevertheless benefit cells exposed to over-production of ROS as occurring in cancer cells, in which triggering of MPT-mediated apoptosis may represent an important defense mechanism to their host.
authors.affiliation: Departamento de Física e Química, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, 14040-903 Ribeirão Preto, SP, Brazil. g031071@yahoo.com
authors.forename: Gilberto L
authors.initials: GL
authors.lastname: Pardo-Andreu
authors.forename: Daniel Junqueira
authors.initials: DJ
authors.lastname: Dorta
authors.forename: René
authors.initials: R
authors.lastname: Delgado
authors.forename: Renata A
authors.initials: RA
authors.lastname: Cavalheiro
authors.forename: Antonio C
authors.initials: AC
authors.lastname: Santos
authors.forename: Anibal E
authors.initials: AE
authors.lastname: Vercesi
authors.forename: Carlos
authors.initials: C
authors.lastname: Curti
mesh_terms: D000818:Animals; D019817:Benzoic Acid / Q000494:pharmacology; D002392:Catechin / Q000494:pharmacology; D016572:Cyclosporine / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D005033:Ethylmaleimide / Q000494:pharmacology; D005707:Gallic Acid / Q000494:pharmacology; D006735:Horseradish Peroxidase / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000494:pharmacology; D031022:Mangifera / Q000737:chemistry*; D008930:Mitochondria, Liver / Q000187:drug effects*; D008933:Mitochondrial Swelling / Q000187:drug effects; D010539:Permeability / Q000187:drug effects*; D010936:Plant Extracts / Q000494:pharmacology*; D051381:Rats; D044004:Xanthones / Q000494:pharmacology*
chemical_list: D010936:Plant Extracts; D044004:Xanthones; C013592:mangiferin; D004533:Egtazic Acid; D005707:Gallic Acid; D016572:Cyclosporine; D002392:Catechin; D019817:Benzoic Acid; D006861:Hydrogen Peroxide; D006735:Horseradish Peroxidase; D005033:Ethylmaleimide