title: 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.
authors.affiliation: Department of Pharmacology, College of Medicine, University of South Florida, Tampa, Florida 33612-4799, USA. dfitzpat@hsc.usf.edu
authors.forename: David F
authors.initials: DF
authors.lastname: Fitzpatrick
authors.forename: Bettye
authors.initials: B
authors.lastname: Bing
authors.forename: David A
authors.initials: DA
authors.lastname: Maggi
authors.forename: Richard C
authors.initials: RC
authors.lastname: Fleming
authors.forename: Rebecca M
authors.initials: RM
authors.lastname: O'Malley
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects; D044946:Biflavonoids; D002392:Catechin / Q000494:pharmacology*; D005591:Chemical Fractionation; D002851:Chromatography, High Pressure Liquid; D004730:Endothelium, Vascular / Q000187:drug effects; D006801:Humans; D008297:Male; D010936:Plant Extracts / Q000494:pharmacology*; D044945:Proanthocyanidins; D051381:Rats; D017207:Rats, Sprague-Dawley; D012639:Seeds / Q000737:chemistry*; D014664:Vasodilation; D014665:Vasodilator Agents / Q000494:pharmacology*; D027843:Vitis / Q000737:chemistry*
chemical_list: D044946:Biflavonoids; D010936:Plant Extracts; D044945:Proanthocyanidins; D014665:Vasodilator Agents; C017674:procyanidin; D002392:Catechin