Delphinidin, an active compound of red wine, inhibits endothelial cell apoptosis via nitric oxide pathway and regulation of calcium homeostasis

• Published in: British journal of pharmacology Vol. 139; no. 6; pp. 1095 - 1102
• Main Authors: Martin, Sophie, Giannone, Grégory, Andriantsitohaina, Ramaroson, Carmen Martinez, M
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.07.2003; Nature Publishing; Wiley
• Subjects: Animals; Anthocyanins - pharmacology; Apoptosis - drug effects; Apoptosis - physiology; Biological and medical sciences; Ca2+ handling; Calcium - physiology; Cattle; Cell death; Cells, Cultured; cGMP; delphinidin; Endothelial Cells - drug effects; Endothelial Cells - physiology; endothelium; Homeostasis - drug effects; Homeostasis - physiology; Life Sciences; MAP kinases; Medical sciences; Nitric Oxide - physiology; Nitric Oxide Synthase - biosynthesis; Nitric Oxide Synthase Type III; Wine; NO; endothelium; Cell death; Ca2+ handling; MAP kinases; cGMP; delphinidin
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1038/sj.bjp.0705347

Epidemiological studies have suggested that moderate consumption of natural dietary polyphenolic compounds might reduce the risk of cardiovascular disease and also protect against cancer. The present study investigates the effects of delphinidin, an anthocyanin present in red wine, on bovine aortic endothelial cells apoptosis. Based on flow cytometry, terminal deoxynucleotidyl transferase‐mediated dUTP nick‐end labeling analysis and detection of mitochondrial cytochrome c release, we show that delphinidin (10−2 g l−1) alone had no effect either on necrosis or on apoptosis, but it significantly reduced apoptosis elicited by actinomycin D (1 μg ml−1, 24 h) and 7β‐hydroxycholesterol (10 μg ml−1, 18 h). The protective effect of delphinidin was abolished by inhibitors of nitric oxide‐synthase (NOS) (L‐NA, 100 μM and SMT, 100 μM), guanylyl cyclase (ODQ, 100 μM) and MAP kinase (PD98059, 30 μM). Western blot analysis and protein detection by confocal microscopy demonstrate that the antiapoptotic effect of delphinidin was associated with an increased endothelial NOS expression mediated by a MAP kinase pathway. Finally, delphinidin alone had no effect on cytosolic‐free calcium ([Ca2+]i), but normalized the changes in [Ca2+]i produced by actinomycin D towards the control values, suggesting that the antiapoptotic effect of delphinidin is associated with the maintenance of [Ca2+]i in the physiological range. All of the observed effects of delphinidin may preserve endothelium integrity, the alteration of which lead to pathologies including cardiovascular diseases, such as atherosclerosis, and is often associated with cancers. In conclusion, the protective effect of delphinidin against endothelial cell apoptosis contributes to understand the potential benefits of a consumption rich in polyphenols. British Journal of Pharmacology (2003) 139, 1095–1102. doi:10.1038/sj.bjp.0705347