Effect of a standardized grape seed extract on low-density lipoprotein susceptibility to oxidation in heavy smokers

Vigna, Giovanni Battista; Costantini, Fabrizio; Aldini, Giancarlo; Carini, Marina; Catapano, Alberico L.; Schena, Fabio; Tangerini, A.; Zanca, R.; Bombardelli, E.; Morazzoni, Paolo; Mezzetti, Andrea; Fellin, Renato; Facino, Roberto Maffei

doi:10.1016/s0026-0495(03)00192-6

Cited by 103 publications

(81 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…An inexpensive GSE standardized to smaller size oligomeric procyanidins and complexed with soy phospholipids into phytosomes to improve bioavailability (leucoselect) is available over the counter. Leucoselect had been shown to improve the total antioxidant capacity of plasma and reduce LDL susceptibility to oxidative stress in heavy smokers (24). As such, we evaluated its efficacy in our preclinical study, using an A549 lung cancer xenograft nude mouse model, and demonstrated significant efficacy in tumor growth inhibition (25).…”

Section: Discussionmentioning

confidence: 99%

Grape Seed Procyanidin Extract Mediates Antineoplastic Effects against Lung Cancer via Modulations of Prostacyclin and 15-HETE Eicosanoid Pathways

Mao

Smoake

Park

et al. 2016

Cancer Prevention Research

View full text Add to dashboard Cite

Grape seed procyanidin extract (GSE) has been reported to exert antineoplastic properties via the inhibition of cyclooxygenase-2 (COX-2)/prostaglandin E 2 (PGE 2 ) eicosanoid pathways. In addition, ample data link carcinogenesis to inflammatory events involving other major eicosanoid metabolic pathways, including prostacyclin (PGI 2 ) and 15-hydroxyeicosatetraenoic acid (15-HETE). We therefore evaluated the effects of GSE on prostacyclin synthase (PTGIS)/PGI 2 and 15-lipoxigenase-2 (15-LOX-2)/15-HETE productions by human lung premalignant and malignant cells and correlated the findings with antiproliferative or proapoptotic effects of GSE. The effects of GSE on PGI 2 and 15-HETE productions by human bronchoalveolar lavage (BAL) cells ex vivo were also determined. We further evaluated the bioactivity of oral administration of leucoselect phytosome (a standardized GSE) in the lungs of subjects participating in a lung cancer chemoprevention trial, by comparing the antiproliferative effects of coculturing matched pre-versus posttreatment BAL fluids with lung premalignant and malignant cells. GSE significantly increased PGI 2 (as measured by 6-keto PGF1a) and 15-HETE productions by these cells. Transfections of PTGIS or 15-LOX-2-specific siRNA partially abrogated the antiproliferative or proapoptotic effects of GSE in lung premalignant and malignant cells, respectively. GSE also increased PTGIS and inhibition of caspase-3, and transfection of 15-LOX-2 siRNA abrogated the GSEinduced apoptosis in A549 cells. In addition, culture supernatants from ex vivo GSE-treated baseline BAL cells, as well as BAL fluids from subjects treated with leucoselect phytosome, significantly decreased proliferations of lung premalignant and malignant cells. Our findings support the continued investigation of GSE as an anti-neoplastic and chemopreventive agent against lung cancer. Cancer Prev Res; 9(12); 925-32. Ó2016 AACR.

show abstract

Section: Discussionmentioning

confidence: 99%

Grape Seed Procyanidin Extract Mediates Antineoplastic Effects against Lung Cancer via Modulations of Prostacyclin and 15-HETE Eicosanoid Pathways

Mao

Smoake

Park

et al. 2016

Cancer Prevention Research

View full text Add to dashboard Cite

show abstract

“…It is known that alcohol has pro-oxidant effects. Studies performed with dealcoholized wine, grapes, and GSE have shown strong antioxidant effects, indicating that the polyphenol content contributes critically to the antioxidant abilities of wine (Young et al 2000, Abu-Amsha Caccetta et al 2001, Bagchi et al 2002, Durak et al 2002, O'Byrne et al 2002, Park et al 2003, Vigna et al 2003, Ko et al 2005, Zern et al 2005, Castilla et al 2006. The antioxidant effects of red wine and of its major polyphenols have been demonstrated with in vitro systems, in cell culture, and in human subjects (Soleas et al 1997, Fernandez-Pachon et al 2006, Modun et al 2008.…”

Section: Antioxidant Effectsmentioning

confidence: 99%

Wine and Health: A Review

Guilford

Pezzuto

2011

Am. J. Enol. Vitic.

166

View full text Add to dashboard Cite

Abstract:As indicated by epidemiological studies, regular and moderate wine consumption, particularly red wine, has been associated with health benefits. Clinical studies and work performed with animal models indicate that wine may protect against cardiovascular disease, atherosclerosis, hypertension, certain types of cancer, type 2 diabetes, neurological disorders, and metabolic syndrome. The mechanism of action has been attributed to antioxidant, lipid regulating, and anti-inflammatory effects. A variety of wine constituents have been studied in various disease models. Both the alcoholic and polyphenolic components of wine are believed to contribute to these beneficial effects. As wine is a complex mixture, it is likely that a multitude of chemical constituents, as well as their metabolites, work synergistically to impact human health. In sum, although wine drinking may be contraindicated in certain individuals, in healthy people, regular consumption of moderate amounts of wine may protect against certain chronic health conditions.

show abstract

“…More recently, there have been reports showing the preservation of serum PON activity and protection against LDL oxidation by wine flavonoids in mice [79,80]. A recent clinical trial demonstrated the beneficial effects of grape extract on the susceptibility of LDL oxidation in heavy smokers [81].…”

Section: Frequency Of Ethanol Intake In Cardioprotectionmentioning

confidence: 99%

Is alcohol beneficial or harmful for cardioprotection?

et al. 2009

View full text Add to dashboard Cite

While the effects of chronic ethanol consumption on liver have been well studied and documented, its effect on the cardiovascular system is bimodal. Thus, moderate drinking in many population studies is related to lower prevalence of coronary artery disease (CAD). In contrast, heavy drinking correlates with higher prevalence of CAD. In several other studies of cardiovascular mortalities, abstainers and heavy drinkers are at higher risk than light or moderate drinkers. The composite of this disparate relation in several population studies of cardiovascular mortality has been a ''U-'' or ''J-''shaped curve. Apart from its ability to eliminate cholesterol from the intima of the arteries by reverse cholesterol transport, another major mechanism by which HDL may have this cardioprotective property is by virtue of the ability of its component enzyme paraoxonase1 (PON1) to inhibit LDL oxidation and/or inactivate OxLDL. Therefore, PON1 plays a central role in the disposal of OxLDL and thus is antiatherogenic. Furthermore, PON1 is a multifunctional antioxidant enzyme that can also detoxify the homocysteine metabolite, homocysteine thiolactone (HTL), which can pathologically cause protein damage by homocysteinylation of the lysine residues, thereby leading to atherosclerosis. We demonstrated that moderate alcohol up regulates liver PON1 gene expression and serum activity, whereas heavy alcohol consumption had the opposite effects in both animal models and in humans. The increase in PON1 activity in light drinkers was not due to preferential distribution of high PON1 genotype in this group. It is well known that wine consumption in several countries shows a remarkable inverse correlation to local rates of CAD mortality. Significantly, apart from its alcohol content, red wine also has polyphenols such as quercetin and resveratrol that are also known to have cardioprotective effects. We have shown that quercetin also up regulates PON1 gene in rats and in human liver cells. The action of quercetin seems to be mediated via the active form of the nuclear lipogenic transcription factor, sterol-regulatory element-binding protein 2 (SREBP2) that is translocated from endoplasmic reticulum to the nucleus. However, the mechanism of action of ethanol-mediated up-regulation of PON1 gene remains to be elucidated. We conclude that both moderate ethanol and quercetin, the two major components of red wine, exhibit cardioprotective properties via the up-regulation of the antiatherogenic gene PON1.

show abstract

Effect of a standardized grape seed extract on low-density lipoprotein susceptibility to oxidation in heavy smokers

Cited by 103 publications

References 48 publications

Grape Seed Procyanidin Extract Mediates Antineoplastic Effects against Lung Cancer via Modulations of Prostacyclin and 15-HETE Eicosanoid Pathways

Grape Seed Procyanidin Extract Mediates Antineoplastic Effects against Lung Cancer via Modulations of Prostacyclin and 15-HETE Eicosanoid Pathways

Wine and Health: A Review

Is alcohol beneficial or harmful for cardioprotection?

Contact Info

Product

Resources

About