Scientific Publication of Olive Polyphenols and Hydroxytyrosol

Genes Nutr. 2011 Sep 28. [Epub ahead of print]

Investigation into the biological properties of the olive polyphenol, hydroxytyrosol: mechanistic insights by genome-wide mRNA-Seq analysis.

Rafehi H, Smith AJ, Balcerczyk A, Ziemann M, Ooi J, Loveridge SJ, Baker EK, El-Osta A, Karagiannis TC.

Source

Epigenomic Medicine, Baker IDI Heart and Diabetes Institute, The Alfred Medical Research and Education Precinct, 75 Commercial Road, Melbourne, VIC, Australia.

Abstract

The medicinal properties of the leaves and fruit of Olea Europaea (olive tree) have been known since antiquity. Numerous contemporary studies have linked the Mediterranean diet with increased health. In particular, consumption of olive oil has been associated with a decreased risk of cardiovascular disease and certain cancers. Increasingly, there has been an interest in the biological properties of polyphenols, which are minor constituents of olive oil. For example, hydroxytyrosol has been shown to be a potent antioxidant and has anti-atherogenic and anti-cancer properties. The overall aim of this study was to provide insights into the molecular mechanisms of action of hydroxytyrosol using genome-wide mRNA-Seq. Initial experiments were aimed at assessing cytotoxicity, apoptosis and cell cycle effects of hydroxytyrosol in various cell lines. The findings indicated a dose-dependent reduction in cell viability in human erythroleukemic K562 and human keratinocytes. When comparing the viability in parental CEM-CCRF and R100 cells (which overexpress the P-glycoprotein pump), it was determined that the R100 cells were more resistant to effects of hydroxytyrosol suggesting efflux by the multi-drug resistance pump. By comparing the uptake of Hoechst 33342 in the two cell lines that had been pretreated with hydroxytyrosol, it was determined that the polyphenol may have P-glycoprotein-modulating activity. Further, initial studies indicated modest radioprotective effects of relatively low doses of hydroxytyrosol in human keratinocytes. Analysis of mRNA sequencing data identified that treatment of keratinocytes with 20 μM hydroxytyrosol results in the upregulation of numerous antioxidant proteins and enzymes, including heme oxygenase-1 (15.46-fold upregulation), glutaredoxin (1.65) and glutathione peroxidase (1.53). This may account for the radioprotective activity of the compound, and reduction in oxidative stress suggests a mechanism for chemoprevention of cancer by hydroxytyrosol. Alteration in the expression of transcription factors may also contribute to the anti-cancer effects described in numerous studies. These include changes in the expression of STAT3, STAT6, SMAD7 and ETS-1. The telomerase subunit TERT was also found to be downregulated in K562 cells. Overall, our findings provide insights into the mechanisms of action of hydroxytyrosol, and more generally, we identify potential gene candidates for further exploration.

PMID:

21953375

[PubMed - as supplied by publisher]

For more information please visit: http://www.ncbi.nlm.nih.gov/pubmed/21953375

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Europe’s EFSA validates CREAGRI®, Inc. claims about Olive Polyphenol efficacy in protecting LDL particles from oxidative damage.

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It marks a milestone in the history of dietary supplements and it is the first time that something other than olive oil is formally recognized as a viable source of hydroxytyrosol and antioxidant polyphenol

WEBWIRE – Thursday, September 15, 2011

Hayward, Sept. 14, 2011 - First reported in a 1999 study by Francesco Visioli et all on behalf of the Italian Institute of Pharmacological Science, and subsequently supported by 10 years of research in the field of olive polyphenol conducted by CREAGRI® Inc., the notion that olive polyphenol are effective in protecting LDL particles from oxidative damage is now being confirmed by the European Food Safety Authority (EFSA).
Following on a request by the European Commission, on 4/8/20, EFSA’s Panel on Dietetic Products, Nutrition and Allergies has concluded that a cause/effect relationship has been established between the consumption of olive polyphenol (standardized by the content of hydroxytyrosol and its derivatives) and protection of LDL particles from oxidative damage. The olive constituents subject to the health claims include the olive fruit, olive mill waste waters, olive oil and olive leafs, and is supported for polyphenol such as hydroxytyrosol and oleuropein.
The panel has also established that to benefit from olive polyphenol’s antioxidant properties, a minimum of 5 mg of hydroxytyrosol and its derivatives should be consumed daily. The panel noted also that the concentrations of polyphenol’s in some olive oil maybe too low to allow for the consumption of the suggested minimum dosage.
“This is the validation of CREAGRI®’s decade long research with the use of olive polyphenol derived from the juice of organic olives to improve cardiovascular health, and to manage cholesterol,” affirms Roberto Crea, CREAGRI®’s founder and CEO, “It marks a milestone in the history of dietary supplements and it is the first time that something other than olive oil is formally recognized as a viable source of hydroxytyrosol and antioxidant polyphenol. The stamp of approval of the top European Safety Authority for dietary supplements can now be attached to hydroxytyrosol based ingredients and products such as Hidrox™ and Olivenol™ Plus. In addition, it opens the unique opportunity for companies (especially CREAGRI®) to expand on beneficial claims based upon positive clinical experience”.
CREAGRI®, which produces Hidrox™, a patented formulation of hyrdroxytyrosol, and the Olivenol™ Plus line of dietary supplements, has been at the forefront of the research and the development of products featuring the power olive polyphenol, and had already established almost 7 years ago that hydroxytyrosl is effective at concentrations as low as 5 mg per daily serving. In recognition of CREAGRI®’s leadership in the field of antioxidant polyphenol recently Nutraceutical Business Technology magazine has named the company among the finalists for the NBT Awards in two categories: Most Innovative Ingredient; and Outstanding Application in Health Management. One of the most sought after awards in the nutraceutical industry the NBT Awards are bestowed on companies which express a clear leadership in their field of activity and have a knack for innovation. The awards will be conferred on May 11, 2001 in Geneva during the VitaFoods Europe Exhibit and Conference.
About Hidrox
HIDROX™ is CREAGRI®’s trademarked hydroxytyrosol formulation, a powerful polyphenol scientifically recognized for its anti-oxidant properties and efficacy in heart and joint health. HIDROX™ is the only olive polyphenol formulation with GRAS certification, meaning that it has been subjected to the most comprehensive set of safety and clinical efficacy tests. HIDROX™ is also covered by the largest number of international patents for applications that include hydroxytyrosol and olive polyphenol. It is available in three forms to fulfill a variety of applications: HIDROX™ 12% Total Polyphenol (6% hydroxytyrosol) freeze dried powder, HIDROX™ 6% Total Polyphenol (3% hydroxytyrosol) powder and liquid HIDROX™ 0.5% total Polyphenol. All products are available in volumes ranging from kilograms to metric tons and can be ordered directly from CREAGRI®.
ABOUT Olivenol™ Plus 2X
A stronger formulation of the already popular Olivenol™ line of dietary supplements, the new Olivenol™ Plus 2X is the latest result of the safety and efficacy research conducted by CREAGRIⓇ in the field of olive polyphenol and hydroxytyrosol. Totally safe, natural and derived from the juice of organic olives, each capsule Olivenol™ Plus 2X delivers double the concentration of hydroxytyrosol and sets a new bar for any existing dietary supplement available on the market today for a true, bioavailable antioxidant, anti-inflammatory and immune modulating natural formula.
About CREAGRI
CREAGRI® Inc., a California company, is the leading manufacturer of HIDROX®, a proprietary hydroxytyrosol-rich ingredient. Its goal is to promote health and wellness by creating superior natural products that strike a balance between nature and technology. The company develops science-based processes that are environmentally friendly and compatible with sustainable agricultural methods.
ABOUT The NBT Awards
The NBT Awards, in partnership with Vitafoods, recognize excellence in R&D, marketing, business and technology within the nutraceutical industry, across the entire sector, looking at ingredients, production, finished products, applications and business practices. The mission is to deliver a set of benchmarks that will provide a pan-European/global audience of nutraceutical professionals the opportunity to recognize significant developments in quality of service, health management, research and development, and relationship management, and will also provide a recognized and tangible reward for the successful companies.
ABOUT EFSA
The European Food Safety Authority (EFSA) is the keystone of European Union (EU) risk assessment regarding food and feed safety. In close collaboration with national authorities and in open consultation with its stakeholders, EFSA provides independent scientific advice and clear communication on existing and emerging risks.
For more information about CREAGRI®, visit www.CREAGRI.com
For more information about OLIVENOL™ Plus 2X, visit www.olivenolplus.com
For more information about the awards visit http://www.nbtawards.com/nbta/index.html
For more information about EFSA visit www.efsa.europa.eu

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Hydroxytyrosol Inactivates Staphyloccoccus aureus Bacteria and Staphylococcal Enterotoxin A

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USDA Say CREAGRI HIDROX® Effective Against Staphylococcus aureus Bacteria and Staphylococcus Enterotoxin A

A ground-breaking research conducted at the Albany, California, Western Regional Center, by a group of USDA researchers has found that HIDROX®, CREAGRI Inc. hydroxytyrosol based formulation of olive polyphenols, inactivates both Staphylococcus aureus pathogens and the toxin produced by these pathogens.
 

	For the complete article please visit: http://www.ars.usda.gov/research/publications/publications.htm?seq_no_115=265117 Research Project: MOLECULAR BIOLOGY AND GENOMICS OF FOODBORNE PATHOGENS Location: Produce Safety and Microbiology Research Title: The Olive Compound 4-Hydroxytyrosol Inactivates Staphyloccoccus aureus Bacteria and Staphylococcal Enterotoxin A (SEA) Authors FRIEDMAN, MENDEL RASOOLY, REUVEN DO, PAULA HENIKA, PHILIP Submitted to: Journal of Food Science Publication Type: Peer Reviewed Journal Publication Acceptance Date: July 25, 2011 Publication Date: N/A Interpretive Summary: Staphylococcus aureus is a major bacterial pathogen that develops resistance to medical antibiotics. It has been reported to cause clinical infections and contamination of a broad variety of foods, including canned mushroom, breaded chicken products, cheese, and raw milk as well on handles of shopping carts causing 185 000 cases of foodborne illnesses in the United States each year. Staphylococcus aureus produces the virulent staphylococcal enterotoxin A, a single chain protein which consists of 233 amino acid residues. It has been estimated that the toxin that is secreted by the bacteria is associated with 78% of staphylococcal outbreaks. The results of the present study show that the pure olive compound 4-hydroxytyrosol inactivated both Staphylococcus aureus pathogens and the toxin produced by these pathogens. A commercial organic olive powder donated by the producer, the CreAgri Company, Hayward, California, also inactivated the pathogens. However, because it was cytotoxic to the spleen cells used in the assay, it was not possible to separate the antimicrobial from the antitoxin effects. The described findings suggest that olive compounds have the potential to counteract adverse effects caused by Staphylococcus aureus bacteria and the virulent toxin produced by these pathogens. To our knowledge, this is the first report on the potential of a safe, edible plant compound to inactivate both pathogens and toxins. Technical Abstract: The foodborne pathogen Staphylococcus aureus produces the virulent staphylococcal enterotoxin A (SEA), a single chain protein which consists of 233 amino acid residues with a molecular weight of 27,078 Da. SEA is a superantigen that is reported to contribute to animal (mastitis) and human (emesis, diarrhea, atopic dermatitis, arthritis, toxic shock) syndromes. Changes of the native structural integrity may inactivate the toxin by preventing molecular interaction with cell membrane receptor sites of their host cells. In the present study, we evaluated the ability of the pure olive compound 4-hydroxytyrosol and a commercial olive powder called Hidrox-12 prepared by freeze-drying olive juice to inhibit S. aureus bacteria and SEA"s biological activity. Dilutions of both test substances inactivated the pathogens. Two independent cell assays (BrdU incorporation into newly synthesized DNA and glycyl-phenylalanyl-aminofluorocoumarin (GF-AFC) proteolysis) demonstrated that the olive compound also inactivated the biological activity of SEA at concentrations that were not toxic to the spleen cells as determined in the MTT assay. However, efforts to determine inhibition of the toxin by Hidrox-12 were not successful because the olive powder was cytotoxic to the spleen cells at concentrations found to be effective against the bacteria. The results suggest that food-compatible and safe anti-toxin olive compounds can be used to inactivate both pathogens and toxins produced by the pathogens. Project Team MANDRELL, ROBERT - ROB FRIEDMAN, MENDEL LAZO, GERARD QUIÑONES, BEATRIZ FAGERQUIST, CLIFTON - KEITH MILLER, WILLIAM - BILL PARKER, CRAIG Publications Publications Related National Programs Food Safety, (animal and plant products) (108) Last Modified: 09/25/2011

Europe;s EFSA validates CreAgri, Inc research and work of Dr. Roberto Crea.

Europe’s EFSA validates CREAGRI®, Inc. claims about Olive Polyphenol efficacy in protecting LDL particles from oxidative damage

It marks a milestone in the history of dietary supplements and it is the first time that something other than olive oil is formally recognized as a viable source of hydroxytyrosol and antioxidant polyphenol

WEBWIRE – Thursday, September 15, 2011

Hayward, Sept. 14, 2011 - First reported in a 1999 study by Francesco Visioli et all on behalf of the Italian Institute of Pharmacological Science, and subsequently supported by 10 years of research in the field of olive polyphenol conducted by CREAGRI® Inc., the notion that olive polyphenol are effective in protecting LDL particles from oxidative damage is now being confirmed by the European Food Safety Authority (EFSA).

Following on a request by the European Commission, on 4/8/20, EFSA’s Panel on Dietetic Products, Nutrition and Allergies has concluded that a cause/effect relationship has been established between the consumption of olive polyphenol (standardized by the content of hydroxytyrosol and its derivatives) and protection of LDL particles from oxidative damage. The olive constituents subject to the health claims include the olive fruit, olive mill waste waters, olive oil and olive leafs, and is supported for polyphenol such as hydroxytyrosol and oleuropein.

The panel has also established that to benefit from olive polyphenol’s antioxidant properties, a minimum of 5 mg of hydroxytyrosol and its derivatives should be consumed daily. The panel noted also that the concentrations of polyphenol’s in some olive oil maybe too low to allow for the consumption of the suggested minimum dosage.

“This is the validation of CREAGRI®’s decade long research with the use of olive polyphenol derived from the juice of organic olives to improve cardiovascular health, and to manage cholesterol,” affirms Roberto Crea, CREAGRI®’s founder and CEO, “It marks a milestone in the history of dietary supplements and it is the first time that something other than olive oil is formally recognized as a viable source of hydroxytyrosol and antioxidant polyphenol. The stamp of approval of the top European Safety Authority for dietary supplements can now be attached to hydroxytyrosol based ingredients and products such as Hidrox™ and Olivenol™ Plus. In addition, it opens the unique opportunity for companies (especially CREAGRI®) to expand on beneficial claims based upon positive clinical experience”.

CREAGRI®, which produces Hidrox™, a patented formulation of hyrdroxytyrosol, and the Olivenol™ Plus line of dietary supplements, has been at the forefront of the research and the development of products featuring the power olive polyphenol, and had already established almost 7 years ago that hydroxytyrosl is effective at concentrations as low as 5 mg per daily serving. In recognition of CREAGRI®’s leadership in the field of antioxidant polyphenol recently Nutraceutical Business Technology magazine has named the company among the finalists for the NBT Awards in two categories: Most Innovative Ingredient; and Outstanding Application in Health Management. One of the most sought after awards in the nutraceutical industry the NBT Awards are bestowed on companies which express a clear leadership in their field of activity and have a knack for innovation. The awards will be conferred on May 11, 2001 in Geneva during the VitaFoods Europe Exhibit and Conference.


About Hidrox

HIDROX™ is CREAGRI®’s trademarked hydroxytyrosol formulation, a powerful polyphenol scientifically recognized for its anti-oxidant properties and efficacy in heart and joint health. HIDROX™ is the only olive polyphenol formulation with GRAS certification, meaning that it has been subjected to the most comprehensive set of safety and clinical efficacy tests. HIDROX™ is also covered by the largest number of international patents for applications that include hydroxytyrosol and olive polyphenol. It is available in three forms to fulfill a variety of applications: HIDROX™ 12% Total Polyphenol (6% hydroxytyrosol) freeze dried powder, HIDROX™ 6% Total Polyphenol (3% hydroxytyrosol) powder and liquid HIDROX™ 0.5% total Polyphenol. All products are available in volumes ranging from kilograms to metric tons and can be ordered directly from CREAGRI®.


ABOUT Olivenol™ Plus 2X

A stronger formulation of the already popular Olivenol™ line of dietary supplements, the new Olivenol™ Plus 2X is the latest result of the safety and efficacy research conducted by CREAGRIⓇ in the field of olive polyphenol and hydroxytyrosol. Totally safe, natural and derived from the juice of organic olives, each capsule Olivenol™ Plus 2X delivers double the concentration of hydroxytyrosol and sets a new bar for any existing dietary supplement available on the market today for a true, bioavailable antioxidant, anti-inflammatory and immune modulating natural formula.


About CREAGRI

CREAGRI® Inc., a California company, is the leading manufacturer of HIDROX®, a proprietary hydroxytyrosol-rich ingredient. Its goal is to promote health and wellness by creating superior natural products that strike a balance between nature and technology. The company develops science-based processes that are environmentally friendly and compatible with sustainable agricultural methods.


ABOUT The NBT Awards

The NBT Awards, in partnership with Vitafoods, recognize excellence in R&D, marketing, business and technology within the nutraceutical industry, across the entire sector, looking at ingredients, production, finished products, applications and business practices. The mission is to deliver a set of benchmarks that will provide a pan-European/global audience of nutraceutical professionals the opportunity to recognize significant developments in quality of service, health management, research and development, and relationship management, and will also provide a recognized and tangible reward for the successful companies.


ABOUT EFSA

The European Food Safety Authority (EFSA) is the keystone of European Union (EU) risk assessment regarding food and feed safety. In close collaboration with national authorities and in open consultation with its stakeholders, EFSA provides independent scientific advice and clear communication on existing and emerging risks.


For more information about CREAGRI®, visit www.CREAGRI.com

For more information about OLIVENOL™ Plus 2X, visit www.olivenolplus.com

For more information about the awards visit http://www.nbtawards.com/nbta/index.html

For more information about EFSA visit www.efsa.europa.eu

         olive polyphenols
         antioxidant
         EFSA
         LDL
         oxidative

Contact Information

Paolo Pontoniere

Director of Communications and Marketing

Creagri, Inc.

(1) 510-732-6478

ppontoniere@creagri.com

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Benefits of Hydroxytyrosol

Metabolism of the olive oil phenols hydroxytyrosol, tyrosol, and hydroxytyrosyl acetate by human hepatoma HepG2 cells. Journal of Agricultural and Food Chemistry. 2005 December 28;53(26):9897-905
This in vitro study investigated the metabolism of the polyphenols hydroxytyrosol, tyrosol and hydroxytyrosyl acetate by liver cells. The liver cells were incubated for 2 and 18 hours in a culture media with HepG2 liver cells. After 18 hours methylated, glucuronidated and methylglucuronidated forms of hydroxytyrosol were detected. Hydroxytyrosyl acetate was mainly hydrolyzed to free hydroxytyrosol.

Hydroxytyrosol, a natural antioxidant from olive oil, prevents protein damage induced by long-wave ultraviolet radiation in melanoma cells.
Free Radical Biology and Medicine. 2005 April 1;38(7):908-19
In is known that UV-A radiation results in damage to skin cells caused by an increased production of free radicals and depletion of antioxidants. The damage results in increased levels of lipid peroxidation products (TBARS) and abnormal L-isoaspartyl residues. The aim of this in vivo study was to investigate the protective effect of hydroxytyrosol on human melanoma cells exposed to UV-B radiation. The researchers found that hydroxytyrosol reduced lipid peroxidation and other markers of oxidative stress. However, at higher levels of hydoxytyrosol, cell differentiation was stopped. The study concluded that the effect of hydroxytyrosol on melanoma cells depends on the used dosage.

The in vivo fate of hydroxytyrosol and tyrosol, antioxidant phenolic constituents of olive oil, after intravenous and oral dosing of labeled compounds to rats. The Journal of Nutrition. 2001 July;131(7):1993-6
This study used radiolabeling of polyphenols to study the in vivo bioavailability of hydroxytyrosol and tyrosol. The rats were fed with hydroxytyrosol and tyrosol, either dissolved in water or oil. The polyphenols were also injected. The researchers found that the oral bioavailability of hydroxytyrosol was higher when given in olive oil (99 percent) then when dosed as aqueous solution (75 percent). For tyrosol the bioavailability was 98 percent in olive oil and 71 percent in aqueous solution.

Hydroxytyrosol, a phenolic compound from virgin olive oil, prevents  macrophage activation. Naunyn Schmiedebergs Archives of Pharmacology. 2005 June;371(6):457-65
The aim of this study was to determine the effect of hydroxytyrosol on inducible nitric oxide synthase and cyclooxygenase-2 expression in macrophages, which were stimulated with lipopolysaccharide. The researchers found that incubation of macrophages with hydroxytyrosol reduced the inducible nitric oxide synthase and expression of cyclooxygenase-2 mRNA. Hydroxytyrosol also reduced inflammatory indicators. The study concluded that hydroxytyrosol may represent a natural agent for the control of inflammatory genes

Please visit www.phytochemicals.info/abstracts/hydroxytyrosol.php, for more information and complete article.

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