Pomegranate Extract Blocks Ritonavir-Induced Endothelial Dysfunction In Porcine Pulmonary Arteries
Introduction:
While the development of highly active antiretroviral therapy (HAART) has allowed improved survival in patients infected with HIV, the medications themselves have been implicated in the increased incidence of cardiovascular and pulmonary arterial disease observed in these patients. The protease inhibitor ritonavir (RTV) has been shown to cause endothelial dysfunction which is likely mediated through oxidative stress and eNOS downregulation. Pomegranate extract is known to have potent antioxidant properties, and in this study we assessed the effects of pomegranate extract on RTV-induced endothelial dysfunction in porcine pulmonary artery endothelial cells.
Methods:
Myograph analysis was performed on porcine pulmonary artery (PA) rings after treatment for 18 hours with RTV alone or RTV plus varying concentrations of pomegranate extract. The rings were suspended in an organ bath, and a standard pretension was applied; then, the thromboxane analogue U46619 was added to induce maximal vasocontraction. Progressively increasing concentrations of bradykinin were used to induce endothelium-dependent, nitric oxide-derived vasodilation. Endothelium-independent relaxation was measured after sodium nitroprusside (SNP) administration. Lucigenin assay was performed to assess for superoxide anion levels. Porcine PA eNOS mRNA and protein levels were measured using real time PCR and mmunohistochemistry, respectively.
Results:
Maximal contraction was reduced in porcine PA rings by 53% after treatment with RTV (15 µM), which was partially reversed when rings were also incubated in 1% pomegranate extract by 30% (p<0.05). Endothelial-dependent vasorelaxation was likewise reduced by RTV treatment by 21% (p<0.05) in response to bradykinin (10-6 M), and this was again restored in a dose-dependent manner after pomegranate administration. With lucigenin assay, it was determined that treating porcine PA rings with RTV led to a significant increase in superoxide anion production, which was reversed by treatment with 1% pomegranate extract. eNOS mRNA levels were found to be significantly reduced in porcine PA rings treated with RTV, while co-treatment with pomegranate extract at 0.001%, 0.01% and 1% reversed this reduction in a dose-dependent manner. Immunostaining for eNOS revealed diminished endothelial eNOS staining after RTV treatment, which was again reversed when pomegranate extract treatment was done along with RTV.
Conclusions:
Naturally occurring pomegranate juice is a powerful antioxidant, and administration of pomegranate extract can reduce the deleterious effects of RTV in porcine PAs, a process thought to be mediated by an elevation in oxidative stress. These data suggest an exciting new use of pomegranate extract in the prevention of HAART-associated endothelial dysfunction and the sequelae of cardiovascular disease and pulmonary arterial disease in patients being treated with RTV.
Baylor College Of Medicine One Baylor Plaza, BCM391 Surgery (R413) Houston, TX USA
Primary Author - S. M. Weakley1 Additional Author - T. J. Beadle , C. Cheng, X. Wang, J. Jiang, P. Kougias, P. H. Lin, Q. Yao Senior Author - C. Chen
A Spanish pomegranate juice has been chosen by Kansas State University for a worldwide consumer study
The study will assess the properties, quality and consumer acceptance of the fruit juice with more antioxidants than any other on the market.
A Spanish pomegranate juice has been chosen by Kansas State University for a worldwide consumer study.
• The USA is one of the countries in which the cultivation and consumption of the pomegranate and its derivatives (juice, nectar, capsules, beauty products, etc.) has increased the most in recent years.
• The United States, Estonia and Spain, selected for growing the Mollar Elche variety, the most highly valued in the world due to its sweetness, colour and softness of its seeds, will all participate in the study.
• The Grantum plus (1) range of pomegranate juices will be presented on the 26th and 27th of October at the 1st Congress on the Pomegranate to be held in the European Union, organised by Miguel Hernández University, consisting of various conferences in which experts from CSIC (Spanish board for scientific investigations) will explain their latest discoveries regarding the beneficial effects the properties of this fruit can have on our health.
Madrid, 25th October 2010.- Researchers from Kansas State University have chosen Granatum Plus pomegranate juice, developed within the Granatum Europa project, from among juices from all over the world for a worldwide consumer study.
This comparative study will be carried out using three brands of juice produced in the United States, one from the European Union (Granatum Plus) and an Estonian brand. Among the American juices are those with the highest number of consumers, such as the brand Pom Wonderful (2), which has launched a surprising television advertising campaign in the United States this October, worth 10 million dollars and inspired upon the garden of Eden and Greek mythology.
Granatum Plus pomegranate juice has been chosen due to its quality and the fact that it is made exclusively using pomegranates of the Mollar Elche variety, grown in the Valencia and Murcia regions, the most valued type of pomegranate in the world thanks to its unique sweetness, colour and the softness of its seeds, making Mollar Elche the perfect variety for producing all kinds of derivatives that enable it to be consumed all year round.
Joining Kansas State University (3) in the study are Tallin University (Estonia) (4), and the Food Quality and Safety Group from Miguel Hernández University, Elche (5), led by Prof. Ángel Carbonell.
According to Prof. Carbonell, “The researchers from the Sensory Analysis Center at Kansas State University were captivated by the pomegranate’s potential during a visit they paid us in early 2009. Since then, they haven’t stopped investigating and investing their knowledge, time and money in this fruit and its derivative products, mainly juice. Their first task was to come up with specific vocabulary to be able to give a precise description of the sensory properties of pomegranate juice (colour, smell, flavour, aftertaste, etc). Now they are about to carry out a study with over 300 consumers, involving 5 juices that they have chosen from around the world. With the data from this study, they will be able to decide which properties or attributes of pomegranate juice are most highly valued by the European and/or American consumer. It is important to understand the characteristics of the appearance and flavour of pomegranate juice so that companies in that sector can use these attributes in the development of their products (with a high guarantee of success), improve their existing products and establish measures for quality control and the shelf-life of the product”.
The pomegranate is a great source of vitamins C and E and minerals and also contains a high amount of polyphenols, meaning that this fruit has a higher level of antioxidants than any other, containing three times more than green tea or red wine.
The Granatum Europa project, formed by Spanish and European food and agriculture companies and Miguel Hernández University, bases the development of its products on research carried out by Miguel Hernández University (Agriculture and Food Technology Department, Food Quality and Safety Group) and by other prestigious scientists from Spanish and European Universities. All of the raw materials used come from crops grown by farming cooperatives in the Valencia and Murcia regions, such as Albafruits and Coopelche. With an annual turnover of 40,000 tonnes, 95% of the pomegranates grown in the European Union are concentrated in these regions. The plant where the pomegranate juice is packaged is located in Archena (Murcia).
Although pomegranates and their derivatives are widely consumed and accepted by European consumers, 99% of the products available in Europe are made from pomegranates grown outside of the European Union. However, Granatum Plus only make products from pomegranates grown in Spain.
According to Eduardo Vidal, Granatum Europa Project Manager, “this study offers a unique opportunity for our project, as well as for Spanish agriculture. It is important for the consumer to be aware of the properties of the pomegranate and its derivatives and in this sense, Miguel Hernández University has made a great effort by organising the 1st National Pomegranate Conference (6) this coming 26th and 27th of October, where researchers from CSIC and CEBAS (Centre for edaphology and applied biology) in the Murcia region, one of the pioneers and leading centres in the world in advances in research into the properties of the pomegranate (7), and Dr. Gilberto Chéchile, head uroandrologist from the Institute for Prostate Diseases, at the Dexeus Institute in Barcelona (8), will hold several conferences in which they explain the pharmacological, neurological, therapeutical, urological and anti-inflammatory benefits, among others, of this 100% Spanish fruit. At the congress, there will be an official presentation of the Granatum plus product range, the first European brand to market juices, nectars, syrups, capsules, etc. made exclusively from pomegranates grown within the borders of the European Union.
The Food Quality and Safety Group at Miguel Hernández University, Elche, have revealed in a recent study carried out with capsules containing pomegranate skin extract that:
The Mollar Elche variety of pomegranate has 10 times more antioxidant capacity in its skin than in its edible interior. • The project “Granatum Europa”, in collaboration with Miguel Hernández University, promotes the consumption of the pomegranate and derived products which triple the antioxidant power of green tea or red wine. • For the first time, products made from Mollar Elche pomegranates cultivated in Spain will be made available to Spanish consumers. • The pomegranate is a great source of vitamin C and E and potassium, as well as containing the polyphenols responsible for its high level of antioxidant activity. • At 40,000 tonnes a year, 95% of the production of pomegranates in the European Union is concentrated in Alicante.
Madrid, 25nd of June 2010. The study, carried out by the Food Quality and Safety Group of Miguel Hernández University, Elche (UMH), in collaboration with the laboratories Antioxidantes Naturales del Mediterráneo in Murcia, a member of the “Granatum Europa” project, has shown that the pomegranate’s greatest antioxidant capacity is in its skin and not in its edible centre as believed up to now.
The pomegranate is a great source of vitamin C and E and minerals like potassium, as well as containing the polyphenols responsible for its high level of antioxidant activity, the main component of which are punicalagins. The antioxidant power of the pomegranate is almost three times greater than that of green tea or red wine. “Granatum Plus” capsules, made exclusively from Mollar Elche pomegranates grown in Spain, contain around 30% punicalagins with 50% polyphenols and around 80% pomegranate extract.
According to Professor Ángel Carbonell of UMH who has led this research “Taking one “Granatum Plus” capsule would equate to drinking 100 ml of juice squeezed from fruit of this variety. This research, along with other research carried out in recent years by prestigious universities around the world, has come to show that the antioxidant capacity of the pomegranate’s skin is 10 times higher than that of its edible interior.”
The project Granatum Europa, formed by Spanish and European food technology companies and Miguel Hernández University, combines both research and development.
With an investment of 5 million Euros, Granatum Europa develop their products based upon research carried out by Miguel Hernández University (Food Technology Department, Food Quality and Safety Group) directed by Professor Ángel Carbonell and other prestigious scientists from Spanish and European universities. All of the prime materials used come from farming cooperatives in the Alicante province which, with a volume of 40,000 tonnes a year, make up 95% of the pomegranates cultivated in the European Union.
According to Dr. Ruiz de la Roja, urologist and director of the Madrid Urological Institute, “the antioxidant polyphenols contained in the pomegranate’s skin and fruit, such as ellagic acid, have not only proven to interfere with the development of prostate cancer, but it has also been shown that their effect goes beyond that, increasing the production of nitric oxide in the blood vessels, improving the circulation of the blood on all levels, meaning that heart and sexual functions are improved.”
The pomegranate, which originates from the Middle East, is produced in many other countries, particularly Mediterranean countries, Spain being the top producer of pomegranates in Europe, and their production is almost exclusive to the Valencia region, especially Elche and the surrounding area.
For Eduardo Vidal, project manager, “this research implies significant progress as the extract taken from the skin of the Granatum Plus pomegranate is soluble and will serve to enrich the products that we are working on such as juices, nectars, jams, syrups and capsules, all from pomegranates cultivated in Spain.”
Although pomegranates and derived products are widely consumed and accepted by a proportion of European consumers, 99% of the products available in our country are made from pomegranates originating from outside of the borders of the European Union. The Granatum Plus product line will be the first to go on the market which is made from pomegranates cultivated in Spain.
Professor of Medicine and Public Health of the Centre for Human Nutrition of the University of California, David Heber, in the prologue to the book “Pomegranates: Ancient Roots to Modern Medicine” assures that “The biochemistry of the pomegranate is fascinating, and the classes of components that it contains are highly varied. The reddish purple colour of the anthocyanins gives the skin its intense colour. Anthocyanins are also found in the arils (the term for the scientific part of widely consumed plants, including their flesh and seeds), together with remains of a family of astringent compounds known as hydrolysable tannins. The pomegranate juice, which is made from the fruit as a whole, is a rich source of polyphenol antioxydants and an ellagitannin known as punicalagin.”
