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Life Extension Magazine June 2012


Pomegranate juice protects nitric oxide against oxidative destruction and enhances the biological actions of nitric oxide.

Pomegranate juice (PJ), which is a rich source of potent flavonoid antioxidants, was tested for its capacity to protect nitric oxide (NO) against oxidative destruction and enhance the biological actions of NO. Employing chemiluminescence headspace analysis, PJ was found to be a potent inhibitor of superoxide anion-mediated disappearance of NO. PJ was much more potent than Concord grape juice, blueberry juice, red wine, ascorbic acid, and DL-alpha-tocopherol. As little as 3 microl of a 6-fold dilution of PJ, in a reaction volume of 5,000 microl, produced a marked antioxidant effect, whereas 300 microl of undiluted blueberry juice or nearly 1,000 microl of undiluted Concord grape juice were required to produce similar effects. PJ and other antioxidant-containing products were found to augment the anti-proliferative action of NO (DETA/NO) on vascular smooth muscle cell (rat aorta) proliferation. PJ was much more effective than the other products tested and elicited no effects when tested alone in the absence of added NO. Similarly, neither PJ nor the other products enhanced the anti-proliferative action of alpha-difluoromethylornithine, a stable substance that inhibits cell growth by NO-independent mechanisms. In order to determine whether PJ is capable of increasing the production of NO by vascular endothelial cells, PJ was tested for its capacity to upregulate and/or activate endothelial NO synthase (eNOS) in bovine pulmonary artery endothelial cells. PJ elicited no effects on eNOS protein expression or catalytic activity. Moreover, PJ did not enhance promoter activity in the eNOS gene (COS-7 cells transfected with eNOS). These observations indicate that PJ possesses potent antioxidant activity that results in marked protection of NO against oxidative destruction, thereby resulting in augmentation of the biological actions of NO.

Nitric Oxide. 2006 Sep;15(2):93-102

Effects of pomegranate juice consumption on myocardial perfusion in patients with coronary heart disease.

Pomegranate juice contains antioxidants such as soluble polyphenols, tannins, and anthocyanins and may have antiatherosclerotic properties. However, no study has investigated the effects of pomegranate juice on patients who have ischemic coronary heart disease (CHD). We investigated whether daily consumption of pomegranate juice for 3 months would affect myocardial perfusion in 45 patients who had CHD and myocardial ischemia in a randomized, placebo-controlled, double-blind study. Patients were randomly assigned into 1 of 2 groups: a pomegranate juice group (240 ml/day) or a placebo group that drank a beverage of similar caloric content, amount, flavor, and color. Participants underwent electrocardiographic-gated myocardial perfusion single-photon emission computed tomographic technetium-99m tetrofosmin scintigraphy at rest and during stress at baseline and 3 months. Visual scoring of images using standardized segmentation and nomenclature (17 segments, scale 0 to 4) was performed by a blinded independent nuclear cardiologist. To assess the amount of inducible ischemia, the summed difference score (SDS) was calculated by subtracting the summed score at rest from the summed stress score. The experimental and control groups showed similar levels of stress-induced ischemia (SDS) at baseline (p >0.05). After 3 months, the extent of stress-induced ischemia decreased in the pomegranate group (SDS -0.8 +/- 2.7) but increased in the control group (SDS 1.2 +/- 3.1, p <0.05). This benefit was observed without changes in cardiac medications, blood sugar, hemoglobin A1c, weight, or blood pressure in either group. In conclusion, daily consumption of pomegranate juice may improve stress-induced myocardial ischemia in patients who have CHD.

Am J Cardiol. 2005 Sep 15;96(6):810-4

Cardioprotective effect of whole fruit extract of pomegranate on doxorubicin-induced toxicity in rat.

CONTEXT: Cardioprotective effects of various plants are generally attributed to their antioxidant activity. The whole fruit extract of pomegranate (WFEP), Punica granatum L. (Punicaceae), has a potent antioxidant activity. Objective: To investigate cardioprotective effect of WFEP against doxorubicin (Dox)-induced cardiotoxicity in rats. MATERIALS AND METHODS: Male Wistar rats were divided randomly into three groups of eight rats each: control (water, 5 mL/kg); Dox (10 mg/kg i.v.) and WFEP (100 mg/kg). Dox was administered in Dox and WFEP groups. After anesthetizing the animals on the last day, electrocardiogram was recorded and blood was analyzed for creatine kinase-MB isoenzyme (CK-MB), lactate dehydrogenase (LDH) and aspartate aminotransferase (AST) activities. Determinations of superoxide dismutase (SOD), reduced glutathione (GSH), lipid peroxidation (LPO) and histopathology of the heart tissues were carried out. RESULTS: The WFEP group showed decreased QT and increase in heart rate (p < 0.05) compared to the Dox group. Significant decrease in CK-MB (p < 0.01), LDH (p < 0.05) and no such significant decrease in AST were observed as compared to the Dox group. There was significant increase in the level of GSH (p < 0.05), whereas inhibition of LPO and increase in SOD concentration was not significant in the WFEP group compared to the Dox group. Histopathological study of the WFEP-treated group showed slight protection against myocardial toxicity induced by Dox. CONCLUSION: Results indicate that WFEP has cardioprotective effect against Dox-induced cardiotoxicity in rats.

Pharm Biol. 2011 Apr;49(4):377-82

Acute and long term effects of grape and pomegranate juice consumption on endothelial dysfunction in pediatric metabolic syndrome.

BACKGROUND: This study aimed to determine the short- and long-term effects of consumption of grape and pomegranate juices on markers of endothelial function and inflammation in adolescents with metabolic syndrome (MetS). METHODS: In a non-pharmacologic randomized controlled trial, 30 individuals were randomly assigned to two groups of drinking natural grape or pomegranate juice for 1 month. Measurements of inflammatory factors [Hs-CRP, sE-selectin, sICAM-1, sVCAM, and interleukin 6 (IL-6)] and flow-mediated dilation (FMD) were made at baseline, 4 hours after first juice consumption and after one month of juice consumption. RESULTS: The percent changes of FMD were significant in both groups in the short- and long-term. Hs-CRP had a nonsignificant decrease. sE selectin had a significant decrease after 4 hours in total and in the pomegranate juice group, followed by a significant decrease after 1 month in both groups. After 4 hours, sICAM-1 significantly decreased in the pomegranate juice group, and after 1 month it decreased in total and pomegranate juice group. Interleulkin-6 (IL-6) had a significant constant decrease at 4-hour and 1-month measurements after drinking pomegranate juice, and in both groups after 1 month. Significant negative correlations of changes in sICAM-1 and sE-selectin with changes in FMD were found in both periods of follow-up; and at 1 month for IL-6. CONCLUSIONS: Decline in inflammation was associated with improvement in FMD without changes in conventional risk factors. Daily consumption of natural antioxidants may improve endothelial function in adolescents with MetS.

J Res Med Sci. 2011 Mar;16(3):245-53

Acute and long-term effects of grape and pomegranate juice consumption on vascular reactivity in paediatric metabolic syndrome.

OBJECTIVES: This study, which to the best of our knowledge is the first of its kind, aimed to determine the acute and long-term effects of the consumption of grape and pomegranate juices on endothelium function in adolescents with metabolic syndrome, and to compare the effects of these two kinds of juices. METHODS: This randomised controlled clinical trial was conducted in 2008 among 30 adolescents, aged 12-15 years, with metabolic syndrome. Participants were randomly assigned to two groups of equal number; one group was asked to drink 18 millilitre per kilogram per day of natural grape juice and the other group was asked to drink 240 millilitre per day of natural pomegranate juice once daily for 1 month. Juices were homemade without any added sweetener. Basal brachial artery dimension and flow-mediated dilation as an index of endothelial function and endothelial-dependent dilation after receiving nitoglycerin spray were evaluated by high-resolution B mode ultrasonography before juice consumption, 4 hours and 30 days after regular daily consumption. RESULTS: Flow-mediated dilation at 90 seconds and after nitoglycerin significantly improved at 4 hours and at 1 month after drinking both kinds of juices, without significant difference between the two groups. The change at 1 month versus 4 hours was significant only in the grape juice group. CONCLUSION: Daily consumption of diets rich in antioxidants might improve endothelial function in adolescents with metabolic syndrome. These effects began as soon as 4 hours after juice consumption. Such beneficial effects should be considered in dietary recommendations for the paediatric age group, notably in obese individuals.

Cardiol Young. 2010 Feb;20(1):73-7

Effects of consumption of pomegranate juice on carotid intima-media thickness in men and women at moderate risk for coronary heart disease.

This randomized, double-blind, parallel trial assessed the influence of pomegranate juice consumption on anterior and posterior carotid intima-media thickness (CIMT) progression rates in subjects at moderate risk for coronary heart disease. Subjects were men (45 to 74 years old) and women (55 to 74 years old) with > or =1 major coronary heart disease risk factor and baseline posterior wall CIMT 0.7 to 2.0 mm, without significant stenosis. Participants consumed 240 ml/day of pomegranate juice (n = 146) or a control beverage (n = 143) for up to 18 months. No significant difference in overall CIMT progression rate was observed between pomegranate juice and control treatments. In exploratory analyses, in subjects in the most adverse tertiles for baseline serum lipid peroxides, triglycerides (TGs), high-density lipoprotein (HDL) cholesterol, TGs/HDL cholesterol, total cholesterol/HDL cholesterol, and apolipoprotein-B100, those in the pomegranate juice group had significantly less anterior wall and/or composite CIMT progression versus control subjects. In conclusion, these results suggest that in subjects at moderate coronary heart disease risk, pomegranate juice consumption had no significant effect on overall CIMT progression rate but may have slowed CIMT progression in subjects with increased oxidative stress and disturbances in the TG-rich lipoprotein/HDL axis.

Am J Cardiol. 2009 Oct 1;104(7):936-42

Effects of pomegranate juice and extract polyphenols on platelet function.

Several studies have shown that polyphenols reduce cardiovascular accidents in high-risk patients; in particular, the inhibition of platelet function may be responsible for part of this benefit. This research studied the antiplatelet effect of Wonderful variety pomegranate (Punica granatum) products, which contain primarily hydrolyzed tannins such as ellagitannins. We have investigated in vitro the effects of treatment with either pomegranate juice (PJ) or the polyphenol-rich extract from pomegranate fruit (POMx) on platelet aggregation, calcium mobilization, thromboxane A(2) production, and hydrogen peroxide formation, induced by collagen and arachidonic acid. PJ and POMx reduce all the platelet responses studied. POMx showed a stronger action in reducing platelet activation; moreover, POMx is active at the concentration that it is possible to obtain after polyphenol-rich food intake (2 microM). These results demonstrated that the cardiovascular health benefits of pomegranate may in part be related to the ability of polyphenols to inhibit platelet function. In fact, PJ and pomegranate extract have similar effects at concentrations expected for normal intake.

J Med Food. 2009 Apr;12(2):334-9

Pomegranate seed oil, a rich source of punicic acid, prevents diet-induced obesity and insulin resistance in mice.

BACKGROUND: Pomegranate seed oil has been shown to protect against diet induced obesity and insulin resistance. OBJECTIVE: To characterize the metabolic effects of punicic acid on high fat diet induced obesity and insulin resistance. DESIGN: High-fat diet or high-fat diet with 1% Pomegranate seed oil (PUA) was fed for 12 weeks to induce obesity and insulin resistance. We assessed body weight and composition (pSABRE DEXA-scan), energy expenditure (Columbus Instruments) and insulin sensitivity at the end of the 12 weeks. RESULTS: PSO intake resulted in a lower body weight, 30.5±2.9 vs 33.8±3.2 g PSO vs HFD respectively, p=0.02, without affecting food intake or energy expenditure. The lower body weight was fully explained by a decreased body fat mass, 3.3±2.3 vs 6.7±2.7 g for PSO and HFD fed mice, respectively, p=0.02. Insulin clamps showed that PSO did not affect liver insulin sensitivity but clearly improved peripheral insulin sensitivity, 164±52% vs 92±24% for PSO and HFD fed mice respectively, p=0.01. CONCLUSIONS: We conclude that dietary PSO ameliorates high-fat diet induced obesity and insulin resistance in mice, independent of changes in food intake or energy expenditure.

Food Chem Toxicol. 2011 Jun;49(6):1426-30

Obesity: The preventive role of the pomegranate (Punica granatum).

Obesity represents a rapidly growing threat to the health of populations in an increasing number of countries. Diet intervention has been proposed as one of the strategies for weight loss and weight maintenance. Traditionally, the pomegranate, including its roots, tree bark, fruit juice, leaves, and flowers, has been used to treat some conditions such as diarrhea, hemorrhage, acidosis, and microbial infections. Pomegranate extracts have been found to have strong anti-inflammatory, antioxidant, and even antitumor properties in vivo and in vitro. More recently, positive effects on fat reduction have been shown using the pomegranate and its extracts. Many of the beneficial effects are related to the presence of anthocyanins, tannins, and very high levels of antioxidants, including polyphenols and flavonoids. Many studies have explored the effects of the pomegranate in obesity, and various mechanisms have been proposed as to how these different extracts help in fat reduction. This article provides an overview of the work done addressing the potential benefits of the pomegranate on obesity and assesses the efficacy of intervention by means of the pomegranate and its extracts. Human studies in this field are still limited and need more attention that would help in understanding the preventive and protective roles pomegranate extracts have on obesity.

Nutrition. 2012 Feb 16