Endothelial dysfunction causes the development of atherosclerosis, which can results in heart health problems such as stroke and heart attacks. The endothelial function is linked with the production of several enzymes including heme oxygenase, dimethylarginine dimethylaminohydrolase and nitric oxide synthase. Heme oxygenase is an enzyme that catalyzes the degradation of heme, resulting in the production of biliverdin, iron, and carbon monoxide. Dimethylarginine dimethylaminohydrolase inhibits the generation of nitric oxide. The nitric oxide synthase is an enzyme that contributes to the immune system and to dilating blood vessels. It plays an important role in maintaining blood pressure homeostasis and vascular integrity. Inducible nitric oxide synthase is found in the cardiovascular system and causes oxidative stress. Endothelial nitric oxide synthase generates nitric oxide in blood vessels and regulates vascular function. Increased nitric oxide expression in endothelial cells may help to ameliorate endothelial dysfunction, harmonize blood pressure, and prevent atherosclerosis.
Treatment of cultured endothelial cells with cyanidin showed favorable protective effects: the levels of endothelial nitric oxide synthase and heme oxygenase were increased in a dose-dependent manner. Higher concentration of the phytochemical, at levels which could hardly be reached in physiological conditions, resulted in the production of inducible nitric oxide synthase and causes oxidative stress. [1] Xu et al. also demonstrated this protective affect on cultured endothelial cells [3]. Treatment of the cells with cyanidin-3-glucoside increased expression of endothelial nitric oxide synthase and an increased production of nitric oxide, up by 100% after a incubation period of 24 hours. Cyanidin-3-glucoside stimulated the phosphorylation of the tyrosine kinase SRC and extracellular signal-regulated kinase 1/2. Drinking of red wine has long been linked to improved heart health. The main flavonoids which are responsible for this possible health benefit are delphinidin and cyanidin, both of which contain hydroxyl residue at position 3'. In an in-vivo study with cultured vascular smooth muscle, these phytochemicals inhibited the formation of reactive oxygen species induced by platelet derived growth factor, a protein which has been linked to the development of atherosclerosis. Delphinidin and cyanidin inhibited expression of vascular endothelial growth factor, induced by platelet derived growth factor, by preventing the activation of the kinases p38 MAPK and JNK [2].
Serraino et al. found that blackberry juice, naturally containing cyanidin-3-O-glucoside, was a scavenger of peroxynitrite and that it exerted a protective effect against peroxynitrite-induced endothelial dysfunction and vascular failure. They found that blackberry juice and found that cyanidin-3-O-glucoside represents about 80% of the total anthocyanin. Cultured endothelial cells, which were exposed to the oxidant peroxynitrite showed a suppression of mitochondrial respiration , an increase in DNA damage and activation of the nuclear enzyme poly-ADP-ribose synthetase (PARS). All these changes were reverted by the addition of blackberry juice. This juice also attenuated in vascular rings the vascular disfunctioning induced by acetylcholine or norepinephrine [4].
[1] Sorrenti V, Mazza F, Campisi A, Di Giacomo C, Acquaviva R, Vanella L, Galvano F. "Heme oxygenase induction by cyanidin 3-O-beta-glucoside in cultured human endothelial cells." Mol Nutr Food Res. 2007 May;51(5):580-6.
[2] Oak MH, Bedoui JE, Madeira SV, Chalupsky K, Schini-Kerth VB. " Delphinidin and cyanidin inhibit PDGF(AB)-induced VEGF release in vascular smooth muscle cells by preventing activation of p38 MAPK and JNK." Br J Pharmacol. 2006 Oct;149(3):283-90.
[3] Xu JW, Ikeda K, Yamori Y. " Upregulation of endothelial nitric oxide synthase by cyanidin-3-glucoside, a typical anthocyanin pigment." Hypertension. 2004 Aug;44(2):217-22.
[4] Serraino I, Dugo L, Dugo P, Mondello L, Mazzon E, Dugo G, Caputi AP, Cuzzocrea S. " Protective effects of cyanidin-3-O-glucoside from blackberry extract against peroxynitrite-induced endothelial dysfunction and vascular failure." Life Sci. 2003 Jul 18;73(9):1097-114.
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