Mitochondrial uptake of anthocyanidins and protection from oxidative stress

Abstract

The anthocyanins show efficient antioxidant properties and free radical scavenging properties which result in various health-promoting benefits. This research investigated the ability of anthocyanidins to distribute into mitochondria and protect mitochondria from oxidative stress. In an in vitro study, the uptake of pure cyanidin and quercetin, and their 3-glucosylated forms into isolated rat liver mitochondria was tested, along with their effects on mitochondrial oxidative stress parameters. The absorption of cyanidin was significantly higher (67% uptake of 125 µM) than the other three flavonoids. Measurements indicated that the cyanidin was taken up into or tightly bound by mitochondria. Also, results suggested that cyanidin uptake was partially dependent on membrane potential. When incubated together (internally and externally) with mitochondria all tested flavonoids decreased reactive oxygen species (ROS) generation during mitochondrial respiration, and inhibited lipid peroxidation to different extents. Importantly, pre-loaded CY showed much stronger effects against oxidative stress in two analyses than other flavonoids. Due to its greater uptake by mitochondria, cyanidin may provide greater protection in vivo. In an in vivo study, cyanidin, quercetin and their 3-glucosides were administered into rat tail vein to give a dose of 7.6 µmol/Kg body weight. Cyanidin and its glucoside had greater affinity to liver and kidney than did quercetin and its glucoside; particularly, all test tissues contained a significantly higher amount of cyanidin than other test flavonoids. Also, cyanidin accumulated more in liver mitochondria than other flavonoids, and consistent with in vitro results was present in mitochondria to a much greater extent than cyanidin glucoside. However, delivery of the flavonoids at this dose did not significantly affect the liver mitochondria susceptibility to lipid peroxidation or the level of endogenous tissue oxidative damage. Altogether the results show that cyanidin can rapidly and efficiently accumulate in mitochondria, wherein it exhibits strong bio-antioxidant activity against oxidative stress and may help protect mitochondrial function and integrity. Also, the anthocyanidin and its 3-glucoside have greater ability than flavonols to accumulate in organs; especially cyanidin presented in liver mitochondria to a much greater extent. Cyanidin could be a potent natural antioxidant compound that is effective in mitochondria-protective therapies.