Ex vivo to in vivo extrapolation of syringic acid and ferulic acid as grape juice proxies for endothelium-dependent vasodilation: Redefining vasoprotective resveratrol of the French paradox

Resveratrol, in wines, has been implicated to be primarily responsible for the French paradox, remaining controversial. Herein, we elucidated the representative vasodilation-increasing polyphenols from concord grape juice (CGJ) using ex vivo-to-in vivo extrapolation (EVIVE). We verified the interference-free antioxidant response of CGJ post-dose supernatant of deproteinated serum (CPSDS, as ex vivo proxy) in isolated aortic rings, and in healthy, and H2O2-treated endothelial cells (H-ECs). Syringic acid and ferulic acid (SF) were detected in CGJ and post-dose rat serum (PRS). In isolated aortic rings and H-ECs, polyphenols alone, or in combination, at doses equivalent to those detected in PRS, quantitatively reflected endothelium-dependent vasodilation of CPSDS, as evidenced by nitric oxide (NO) formation-mediated antioxidation-sensitive activation of Src kinase with subsequent PI3/Akt-dependent phosphorylation of endothelial NO synthase. Using EVIVE, SF closely reflected CGJ in coronary flow-mediated vasodilation. Hence, SF application in precision ethnomedicine may redefine antioxidant-sensitive vasoprotective resveratrol of the French paradox.

Automated summary

The study revealed that syringic acid and ferulic acid in concord grape juice have vasodilation effects in vivo through regulating pathways like nitric oxide and Src kinase. This could potentially redefine the antioxidant-sensitive vasoprotective pathway associated with resveratrol in the French paradox.