Saiko Philipp, Szakmary Akos, Jaeger Walter, Szekeres Thomas
Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Vienna, General Hospital of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria.
Department of Medicine I, Division of Cancer Research, Medical University of Vienna, Borschkegasse 8a, A-1090 Vienna, Austria.
Mutat Res. 2008 Jan-Feb;658(1-2):68-94. doi: 10.1016/j.mrrev.2007.08.004. Epub 2007 Aug 17.
Resveratrol (3,5,4'-trihydroxy-trans-stilbene; RV), a dietary constituent found in grapes and wine, exerts a wide variety of pharmacological activities. Because the grape skins are not fermented in the production process of white wines, only red wines contain considerable amounts of this compound. RV is metabolized into sulfated and glucuronidated forms within approximately 15min of entering the bloodstream, and moderate consumption of red wine results in serum levels of RV that barely reach the micromolar concentrations. In contrast, its metabolites, which may be the active principle, circulate in serum for up to 9h. RV has been identified as an effective candidate for cancer chemoprevention due its ability to block each step in the carcinogenesis process by inhibiting several molecular targets such as kinases, cyclooxygenases, ribonucleotide reductase, and DNA polymerases. In addition, RV protects the cardiovascular system by a large number of mechanisms, including defense against ischemic-reperfusion injury, promotion of vasorelaxation, protection and maintenance of intact endothelium, anti-atherosclerotic properties, inhibition of low-density lipoprotein oxidation, and suppression of platelet aggregation, thereby strongly supporting its role in the prevention of coronary disease. Promising data within the use of RV have also been obtained regarding progressive neurodegenerative maladies such as Alzheimer's, Huntington's, and Parkinson's diseases. Because neurotoxicity is often related to mitochondrial dysfunction and may be ameliorated through the inclusion of metabolic modifiers and/or antioxidants, RV may provide an alternative (and early) intervention approach that could prevent further damage. RV induces a multitude of effects that depend on the cell type (e.g., NF-kappaB modulation in cancer cells vs. neural cells), cellular condition (normal, stressed, or malignant), and concentration (proliferative vs. growth arrest), and it can have opposing activities. RV affects whole pathways and sets of intracellular events rather than a single enzyme and, therefore, may be an effective therapy to restore homoestasis. Nonetheless, the question of whether RV or its metabolites can accumulate to bioactive levels in target organs remains to be addressed.
白藜芦醇（3,5,4'-三羟基反式芪；RV）是一种存在于葡萄和葡萄酒中的膳食成分，具有多种药理活性。由于在白葡萄酒的生产过程中葡萄皮未经过发酵，只有红葡萄酒含有大量这种化合物。RV进入血液后约15分钟内会代谢为硫酸化和葡萄糖醛酸化形式，适量饮用红葡萄酒导致血清中RV水平 barely reach the micromolar concentrations。相比之下，其代谢产物（可能是活性成分）可在血清中循环长达9小时。由于RV能够通过抑制多种分子靶点（如激酶、环氧化酶、核糖核苷酸还原酶和DNA聚合酶）来阻断致癌过程的每一步，因此已被确定为癌症化学预防的有效候选物。此外，RV通过多种机制保护心血管系统，包括抵御缺血再灌注损伤、促进血管舒张、保护和维持完整的内皮、抗动脉粥样硬化特性、抑制低密度脂蛋白氧化以及抑制血小板聚集，从而有力地支持了其在预防冠心病中的作用。在使用RV治疗诸如阿尔茨海默病、亨廷顿病和帕金森病等进行性神经退行性疾病方面也获得了有前景的数据。由于神经毒性通常与线粒体功能障碍有关，并且可能通过添加代谢调节剂和/或抗氧化剂得到改善，RV可能提供一种替代的（早期）干预方法，以防止进一步损伤。RV会产生多种取决于细胞类型（例如癌细胞与神经细胞中的NF-κB调节）、细胞状态（正常、应激或恶性）和浓度（增殖与生长停滞）的效应，并且它可能具有相反的活性。RV影响整个信号通路和一系列细胞内事件，而不是单一酶，因此可能是恢复体内平衡的有效疗法。尽管如此，RV或其代谢产物是否能在靶器官中积累到生物活性水平的问题仍有待解决。
