Vasodilating Procyanidins Derived from Grape Seeds

Abstract

We have shown in previous work that extracts of grape seeds (GSE) and skins, grape juice, and many red wines exhibit endothelium-dependent relaxing (EDR) activity in vitro. This EDR activity involves endothelial nitric oxide (NO) release and subsequent increase in cyclic GMP levels in the vascular smooth muscle cells. The NO/cyclic GMP pathway is known to be involved in many cardiovascular-protective roles. The current study focuses on the isolation and identification of EDR-active compounds (procyanidins) from GSE. Crushed Concord grape seeds were extracted with methanol and the extract was separated into seven fractions (A-G) on a Toyopearl TSK-HW-40 column. EDR-active fractions (D-G) were further separated into 25 individual compound peaks by HPLC, 16 of which were EDR active (threshold for relaxation ranged between less than 0.5 microg/mL and greater than 4 microg/mL). Procyanidin identification was accomplished by electrospray-ion trap mass spectrometry (ES-ITMS), MS/MS, and by tannase treatment and acid thiolysis, followed by HPLC and ES-ITMS of the products. Activity of isolated procyanidins tended to increase with degree of polymerization, epicatechin content, and with galloylation. These EDR-active compounds (many of which also possess antioxidant activity), individually or in the form of wines, juices, or nutritional supplements, may be useful in preventing or treating cardiovascular diseases.

Renoprotective Effect of Grape Seed Extract against Oxidative Stress Induced by Gentamicin and Hypercholesterolemia in Rats

“…64 This study showed that supplementation of GSE to GM or GM HC rats significantly elevated the suppressed plasma levels of NO and cGMP. These results are confirmed by the findings of Fitzpatrick et al 66 GSE reduced platelet aggregation, releasing NO from endothelial cells, activating the guanylate cyclase, increasing the cGMP production, and finally inducing vascular relaxation. 67 Providing both GM and GM HC rats with GSE significantly lowered the elevated superoxide anion and LPO in renal tissue, while it markedly raised the attenuated level of GSH and the activities of SOD, GSH-Px, and CAT.…”

Effects of Grape Seed Proanthocyanidin Extracts on Aortic Pulse Wave Velocity in Streptozocin Induced Diabetic Rats

“…GSPEs were useful in preventing and treating cardiovascular diseases. 45) In summary, chronic hyperglycemia can cause overexpression of the AGE-RAGE system in the aortas of STZ-induced diabetic rats. Hyperglycemia-induced activation of the AGE-RAGE pathway may have an important role in the pathogenesis of diabetic aortic stiffness.…”

Plant derived therapeutics for the treatment of Metabolic Syndrome

“…Interestingly, through bioassay-guided fractionation of crude GSE using the rat aortic vasorelaxation model, increasing EDR activity was demonstrated to correlate with increased concentrations of procyanidin oligomerization [56,57]. This finding suggests that highly polymerized polyphenols (Figure 1f), although not studied extensively in other botanicals, may play a significant role in the hypotensive activities of GSEs [56,57].…”

“…Several in vitro studies have demonstrated endothelium-dependent relaxation (EDR) as the primary mechanism of action for GSE [55][56][57]. Interestingly, through bioassay-guided fractionation of crude GSE using the rat aortic vasorelaxation model, increasing EDR activity was demonstrated to correlate with increased concentrations of procyanidin oligomerization [56,57].…”