Strawberry extract caused endothelium-dependent relaxation through the activation of PI3 kinase/Akt

Polyphenolic compounds are vasodilators and help to lower the risk of cardiovascular diseases. We hypothesized that a freeze-dried strawberry powder that is rich in polyphenolic compounds would cause an endothelium-dependent relaxation (EDR) through the activation of phosphatidylinositol-3 (PI3)-kinase/protein kinase B (Akt) in rabbit aorta. The powder was prepared by freeze drying a homogenate of ripe California strawberry fruits. An aqueous extract of strawberry powder was applied to rabbit aortic rings suspended in organ baths containing Krebs-Henseleit buffer maintained at 37 degrees C. In aortic rings precontacted with norepinephrine, the extract produced a dose-dependent relaxation. The maximum relaxations elicited by the extract (73.1 +/- 1.0%) were similar to those elicited by acetylcholine (68.2 +/- 1.5%) ( n = 14 for each). The relaxation by strawberry extract was abolished by removal of the endothelium and by prior incubation with N omega-nitro- l-arginine methyl ester hydrochloride (L-NAME), confirming the essential role of endothelial nitric oxide synthase (eNOS). The responses to the strawberry were also abolished by incubation with wortmannin and LY294002, which are inhibitors of PI3 kinase. Using immunoblotting, we also demonstrated that the strawberry extract induced the phosphorylation of both Akt and eNOS in human umbilical vein endothelial cells (HUVECs) via PI3 kinase/Akt pathway. Taken together, our novel findings suggest that the EDR induced by the strawberry extract was mediated by activation of the PI3 kinase/Akt signaling pathway, resulting in phosphorylation of eNOS.