Delphinidin, an active compound of red wine, inhibits endothelial cell apoptosis via nitric oxide pathway and regulation of calcium homeostasis.
British Journal of Pharmacology. 2003-07-01; 139(6): 1095-1102
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1. Br J Pharmacol. 2003 Jul;139(6):1095-102.
Delphinidin, an active compound of red wine, inhibits endothelial cell apoptosis
via nitric oxide pathway and regulation of calcium homeostasis.
Martin S(1), Giannone G, Andriantsitohaina R, Martinez MC.
(1)Pharmacologie et Physico-Chimie des Interactions Cellulaires et Moléculaires,
UMR CNRS 7034, Faculté de Pharmacie, Université Louis Pasteur, 67401 Illkirch,
1. 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. 2. 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 micro g ml(-1), 24 h) and
7beta-hydroxycholesterol (10 micro g ml(-1), 18 h). 3. The protective effect of
delphinidin was abolished by inhibitors of nitric oxide-synthase (NOS) (L-NA, 100
micro M and SMT, 100 micro M), guanylyl cyclase (ODQ, 100 micro M) and MAP kinase
(PD98059, 30 micro M). 4. 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. 5. Finally, delphinidin alone had no effect on cytosolic-free calcium
([Ca(2+)](i)), but normalized the changes in [Ca(2+)](i) produced by actinomycin
D towards the control values, suggesting that the antiapoptotic effect of
delphinidin is associated with the maintenance of [Ca(2+)](i) in the
physiological range. 6. 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.
PMID: 12871827 [Indexed for MEDLINE]