Mitochondrial uptake and redox activities of anthocyanins

花青素是一种类黄酮类化合物，可以赋予浆果和红酒以红色/紫色。已知花青素在试管中具有很强的抗氧化活性，食用富含花青素的食物或饮料与防止衰老和与年龄相关的疾病有关，包括大脑中的神经退化。然而，关于花青素的作用方式，哪些花青素是最具保护作用的，在哪些身体器官中是最具保护作用的，以及生物活性是否源于花青素本身或其消化和代谢的生物活性产物，仍存在许多问题。我们假设，一旦进入我们的身体，不含糖的花青素(称为花青素)形式会被我们细胞的线粒体专门吸收，在那里它们积累并发挥抗氧化剂和生物活性。线粒体是膜性细胞器，通过使用我们呼吸的氧气来燃烧我们所吃的燃料，为我们的细胞提供能量，比如肌肉收缩和神经传递。线粒体的效率并不是100%，其中一些氧被转化为超氧化物和过氧化氢等活性氧物种(ROS)，这会破坏线粒体和细胞的组成部分，并可能导致衰老和细胞死亡。如果花青素能够清除或阻止这些ROS的形成，它们就可以帮助保护线粒体和细胞。我们还假设花青素与维生素C和维生素E一起起作用。维生素C是水溶性的，维生素E在膜脂中，花青素是中间体，可能作用于膜的界面。因此，它们可能在所谓的抗氧化网络中协同工作，在这个网络中，花青素将电子从维生素C传递到维生素E，在维生素E中和脂质过氧化基后再生维生素E。在拟议的研究中，我们将研究花青素/花青素在不同生物环境中的稳定性，花青素/花青素的线粒体摄取和活性，以及花青素与维生素C和维生素E的合作能力。我们还将研究一类名为吡喃花青素的花青素，这种花青素存在于波尔图葡萄酒等陈年葡萄酒中，其生物活性研究较少。这些研究将包括使用从大鼠肝脏和大脑分离的线粒体的试管研究，使用培养细胞(肠道细胞、肝细胞和神经元)的研究，以及将花青素输送到食物中或直接进入血液的动物研究。这项研究的结果将加深我们对花色苷生物活性的理解，以及它们限制线粒体来源的氧化应激和年龄相关疾病的能力。这些信息将有助于营养和农业食品界，以及开发营养食品的潜力。

The anthocyanins are a class of flavonoids that give the red/purple colour to berries and red wine. Anthocyanins are known to have strong antioxidant activity in the test tube, and consumption of anthocyanin-rich foods or drinks have been linked to protection from aging and age-related diseases, including neurodegeneration in the brain. However there are many questions as to how anthocyanins might work, which ones are the most protective and in which body organs, and whether the biological activities are due to the anthocyanins themselves or to bioactive products of their digestion and metabolism. We hypothesize that once entering our body, the form of anthocyanins without a sugar attached (called anthocyanidins), are specifically taken up by the mitochondria of our cells, where they accumulate and exert antioxidant and biological activities. Mitochondria are membranous organelles that provide energy to our cells, for things like muscle contraction and neurotransmission, by using the oxygen that we breathe to burn fuels that we eat. Mitochondria are not 100% efficient, and some of the oxygen gets converted to reactive oxygen species (ROS) such as superoxide and peroxides, that are damaging to the mitochondria and components of cells, and may contribute to aging and cell death. If anthocyanidins are able to scavenge or prevent formation of these ROS, they can help protect the mitochondria and the cell. We also hypothesize that anthocyanidins work together with vitamin C and vitamin E. While vitamin C is water soluble and vitamin E is in membrane lipids, anthocyanidins are intermediate and may work at the interface of membranes. Therefore they may work together in what is called an antioxidant network, whereby anthocyanidins pass electrons from vitamin C to vitamin E to regenerate vitamin E after it has neutralized a lipid peroxide radical. In the proposed research we will be investigating the stability of anthocyanins/anthocyanidins in different biological environments, the mitochondrial uptake and activities of anthocyanins/ anthocyanidins, and the ability of anthocyanidins to cooperate with vitamin C and vitamin E. We will also study a class of anthocyanins called pyranoanthocyanins, which are found in aged wines such as port wine, and have been little studied for their biological activities. The studies will include test tube studies using mitochondria isolated from rat liver and brain, studies with cultured cells (intestinal cells, liver cells, and neurons), and animal studies where the anthocyanins are delivered in the food or directly to the blood. The results of this research will advance our understanding of the biological activities of anthocyanins, and their ability to limit mitochondria-derived oxidative stress and age-related diseases. The information will be useful to the nutrition and agri-food communities, and to the potential for developing nutraceuticals.