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维芒(芒果提取物)可诱导分离的线粒体发生通透性转换,与维芒的主要成分芒果苷的作用极为相似。

Vimang (Mangifera indica L. extract) induces permeability transition in isolated mitochondria, closely reproducing the effect of mangiferin, Vimang's main component.

作者信息

Pardo-Andreu Gilberto L, Dorta Daniel Junqueira, Delgado René, Cavalheiro Renata A, Santos Antonio C, Vercesi Anibal E, Curti Carlos

机构信息

Departamento de Física e Química, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, 14040-903 Ribeirão Preto, SP, Brazil.

出版信息

Chem Biol Interact. 2006 Feb 1;159(2):141-8. doi: 10.1016/j.cbi.2005.10.109. Epub 2005 Dec 13.

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.

摘要

线粒体通透性转换(MPT)是一种依赖钙离子、对环孢素A(CsA)敏感的非选择性内膜通透性增加过程。它常与凋亡性细胞死亡相关,可由多种因素或条件诱导,通常涉及活性氧(ROS)。在本研究中,我们证明了在20微摩尔钙离子存在的情况下,芒果提取物(Vimang)可诱导分离的大鼠肝线粒体发生MPT,通过对CsA敏感的线粒体肿胀来评估,这与提取物的主要成分芒果苷的作用极为相似,同时也与MPT相关过程相似,如膜蛋白硫醇的氧化、线粒体膜电位耗散以及细胞器内钙离子释放。Vimang的第二主要成分黄酮类儿茶素也能诱导MPT,尽管程度较轻;Vimang提取物中的次要但仍具代表性的成分没食子酸和苯甲酸,分别表现出低和高的MPT诱导能力。然而,在暴露于过氧化氢/辣根过氧化物酶后,这些化合物的可见光谱并未呈现出先前报道的芒果苷那样的变化。得出的结论是,Vimang诱导的MPT与芒果苷的作用极为相似,并提出这种呫吨酮是提取物MPT诱导能力的主要作用剂,其作用机制是通过芒果苷抗氧化活性产生的产物作用于线粒体膜蛋白硫醇。虽然这种作用可能与Vimang抗氧化活性的有益作用相悖,但它可能对暴露于癌细胞中过量产生的ROS的细胞有益,在癌细胞中,触发MPT介导的凋亡可能是宿主的一种重要防御机制。

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