Mitochondrial uptake and redox activities of anthocyanins

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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.