Effects of a Pomegranate Fruit Extract rich in punicalagin on oxidation-sensitive genes and eNOS activity at sites of perturbed shear stress and atherogenesis

Atherosclerosis is enhanced in arterial segments exposed to disturbed flow. Perturbed shear stress increases the expression of oxidation-sensitive responsive genes (such as ELK-1 and p-CREB). Polyphenolic antioxidants contained in the juice derived from the pomegranate contribute to the reduction of oxidative stress and atherogenesis during disturbed shear stress.

Aim of the study: To evaluate the effects of intervention with the Pomegranate Fruit Extract (PFE) rich in polyphones (punicalagin, which is a potent antioxidant) on ELK-1, p-CREB, and endothelial nitric oxide synthase (eNOS) expression induced by high shear stress in vitro and in vivo.

Results: At the doses used in the study, both the PFE and the regular pomegranate juice concentrate reduced the activation of ELK-1 and p-CREB and increased eNOS expression (which was decreased by perturbed shear stress) in cultured human endothelial cells and in atherosclerosis-prone areas of hypercholesterolemic mice. PFE and pomegranate juice increased cyclic GMP levels while there was no significant effect of both compounds on the conversion of L-arginine to L-citrulline. Administration of these compounds to hypercholesterolemic mice significantly reduced the progression of atherosclerosis and isoprostane levels and increased nitrates. This protective effect was relevant with PFE. Vasomotor reactivity was improved and EC₂₅ values in response to Ach and NONOate were significantly increased in treated mice in comparison to controls.

Conclusion: This study indicates that the proatherogenic effects induced by perturbed shear stress can be also reversed by chronic administration of PFE.

http://cardiovascres.oxfordjournals.org/content/73/2/414.full

Pomegranate: How To Clean Your Arteries With One Simple Fruit

The future of cardiovascular disease prevention and treatment will not be found in your medicine cabinet, rather in your kitchen cupboard or in your back yard growing on a tree.

Pomegranate Found To Prevent Coronary Artery Disease Progression

A new study published in the journal Atherosclerosis confirms that pomegranate extract may prevent and/or reverse the primary pathology associated with cardiac mortality: the progressive thickening of the coronary arteries caused by the accumulation of fatty materials known as atherosclerosis.[i]

Mice with a genetic susceptibility towards spontaneous coronary artery blockages were given pomegranate extract via their drinking water for two weeks, beginning at three weeks of age. Despite the fact that pomegranate treatment actually increased cholesterol levels associated with very low density lipoprotein-sized particles, the treatment both reduced the size of the atherosclerotic plaques in the aortic sinus (the dilated opening above the aortic valve) and reduced the proportion of coronary arteries with occlusive atherosclerotic plaques.

Remarkably, the researchers also found that pomegranate extract treatment resulted in the following beneficial effects:

• Reduced levels of oxidative stress
• Reduced monocytie chemotactic protein-1, a chemical messenger (chemokine) associated with inflammatory processes within the arteries.  
• Reduced lipid accumulation in the heart muscle
• Reduced macrophage infiltration in the heart muscle
• Reduced levels of monocyte chemotactic protein-1 and fibrosis in the myocardium
• Reduced cardiac enlargement
• Reduced ECG abnormalities

How can something as benign and commonplace as a fruit extract reverse so many aspects of coronary artery disease, simultaneously, as evidenced by the study above?  The answer may lie in the fact that our ancestors co-evolved with certain foods (fruits in particular) for so long that a lack of adequate quantities of these foods may directly result in deteriorating organ function.  Indeed, two-time Nobel Prize winner Linus Pauling argued that vitamin C deficiency is a fundamental cause of cardiovascular disease, owing to the fact that our hominid primate ancestors once had year-round access to fruits, and as a result lost the ability to synthesize it. 

Discussion

This study adds to the already extant body of clinical research indicating that pomegranate can help unclog your arteries.  For instance, back in 2004, the journal Clinical Nutrition published the results of a three year clinical trial in an Israeli population, finding that the daily consumption of pomegranate juice reversed carotid artery stenosis by up to 29% within 1 year.  Remarkably, the blockages in the control group increased 9%, indicating that pomegranate's artery unblocking effects were even greater than at first apparent. [ii]

Pomegranate's value in cardiovascular disease is quite broad, as evidenced by the following experimentally confirmed properties:

• Anti-inflammatory: Like many chronic degenerative diseases, inflammation plays a significant role in cardiovascular disease pathogenesis. There are five studies on GreenMedInfo.com indicating pomegranate's anti-inflammatory properties.[iii]
• Blood-Pressure Lowering: Pomegranate juice has natural angiotensin converting enzyme inhibiting properties, [iv] and is a nitric oxide enhancer, two well-known pathways for reducing blood pressure. [v] Finally, pomegranate extract rich in punicalagin has been found reduce the adverse effects of perturbed stress on arterial segments exposed to disturbed flow.[vi]
• Anti-Infective: Plaque buildup in the arteries often involves secondary viral and bacterial infection, including hepatitis C and Chlamydia pneumoniae.[vii] Pomegranate has a broad range of anti-bacterial and anti-viral properties.
• Antioxidant: One of the ways in which blood lipids become heart disease-promoting (atherogenic) is through oxidation. LDL, for instance, may be technically 'elevated' but harmless as long as it does not readily oxidize. Pomegranate has been found to reduce the oxidative stress in the blood, as measured by serum paraoxonase levels.  One study in mice found this decrease in oxidative stress was associated with 44% reduction in the size of atherosclerotic lesions. [viii]

For additional research on pomegranate's heart friendly properties read our article: Research: Pomegranate May Reverse Blocked Arteries

Also, view our dedicated research section on reversing arterial plaque: Clogged Arteries

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Resources

• [i] Aishah Al-Jarallah, Fatima Igdoura, Yi Zhang, Christine B Tenedero, Elizabeth J White, Melissa E Macdonald, Suleiman A Igdoura, Bernardo L Trigatti. The effect of pomegranate extract on coronary artery atherosclerosis in SR-BI/APOE double knockout mice. Atherosclerosis. 2013 May ;228(1):80-9. Epub 2013 Mar 7. PMID: 23528829

• [ii] Michael Aviram, Mira Rosenblat, Diana Gaitini, Samy Nitecki, Aaron Hoffman, Leslie Dornfeld, Nina Volkova, Dita Presser, Judith Attias, Harley Liker, Tony Hayek. Pomegranate juice consumption for 3 years by patients with carotid artery stenosis reduces common carotid intima-media thickness, blood pressure and LDL oxidation. Clin Nutr. 2004 Jun;23(3):423-33. PMID: 15158307

• [iii] GreenMedInfo.com, Pomegranate's Anti-Inflammatory Properties

• [iv] Mahalaxmi Mohan, Harshal Waghulde, Sanjay Kasture. Effect of pomegranate juice on Angiotensin II-induced hypertension in diabetic Wistar rats. Phytother Res. 2009 Dec 17. PMID: 20020514

• [v] Filomena de Nigris, Maria Luisa Balestrieri, Sharon Williams-Ignarro, Francesco P D'Armiento, Carmela Fiorito, Louis J Ignarro, Claudio Napoli. The influence of pomegranate fruit extract in comparison to regular pomegranate juice and seed oil on nitric oxide and arterial function in obese Zucker rats. Nitric Oxide. 2007 Aug ;17(1):50-4. Epub 2007 May 5. PMID: 17553710

• [vi] Filomena de Nigris, Sharon Williams-Ignarro, Vincenzo Sica, Lilach O Lerman, Francesco P D'Armiento, Russell E Byrns, Amelia Casamassimi, Daniela Carpentiero, Concetta Schiano, Daigo Sumi, Carmela Fiorito, Louis J Ignarro, Claudio Napoli. Effects of a pomegranate fruit extract rich in punicalagin on oxidation-sensitive genes and eNOS activity at sites of perturbed shear stress and atherogenesis. Cardiovasc Res. 2007 Jan 15;73(2):414-23. Epub 2006 Sep 1. PMID: 17014835

• [vii] Yasunori Sawayama, Kyoko Okada, Shinji Maeda, Hachiro Ohnishi, Norihiro Furusyo, Jun Hayashi. Both hepatitis C virus and Chlamydia pneumoniae infection are related to the progression of carotid atherosclerosis in patients undergoing lipid lowering therapy.Fukuoka Igaku Zasshi. 2006 Aug;97(8):245-55. PMID: 17087362

• [viii] M Aviram, L Dornfeld, M Rosenblat, N Volkova, M Kaplan, R Coleman, T Hayek, D Presser, B Fuhrman. Pomegranate juice consumption reduces oxidative stress, atherogenic modifications to LDL, and platelet aggregation: studies in humans and in atherosclerotic apolipoprotein E-deficient mice. Am J Clin Nutr. 2000 May ;71(5):1062-76. PMID: 10799367