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ULTIMATE PROTECTOR+ BRUNSWICK LABS ORAC6.0 TEST REPORT

Dr. Hank Liers, PhDHPDI’s new product ULTIMATE PROTECTOR+ is a next generation cell protection formula that simultaneously meets the needs for high levels of Vitamin C, full spectrum antioxidants (high ORAC values), and protective enzyme activators (Nrf2 activators from plant-based polyphenols) in a single product. This potent combination of characteristics distinguishes the formula because no other single product available today offers such complete protection.

All three of ULTIMATE PROTECTOR+‘s components provide significant protection against the various types of free radicals that cause cellular damage in the body. In particular, the full spectrum of antioxidants derived from high ORAC fruits, vegetables, and herbs (as well as Vitamin C) provide extremely powerful exogenous sources of protection against oxidative stress. To obtain a quantitative measure of just how powerful these external sources are we have elected to conduct ORAC testing.

ORAC TESTS

ORAC (standing for “Oxygen Radical Absorption Capacity”) was developed by Brunswick Labs as an analytical tool for estimating the antioxidant capacity of substances. It is an in vitro test that was an important advancement in commercially available analysis of the peroxyl free-radical’s trapping ability of foods and ingredients. It has become a de facto standard in the natural products industry. However, the original ORAC method was considered to be just a starting point for comprehensive antioxidant analysis.

The fact is that there are a variety of “free radicals” that operate in humans — the most important of which are the primary radicals hydroxyl, peroxyl, peroxynitrite, singlet oxygen, and superoxide anion. Brunswick Labs has reported that even though the peroxyl is the major free radical in the body, it represents no more than 27% of the total antioxidant potential of selected fruits and vegetables. In addition, the original ORAC method favors certain antioxidant substances over others (e.g., anthocyanins over carotenoids) due to the use of a single free radical source (peroxyl radical).

These radicals are formed, behave, and are defended against differently. They all contribute to: 1) a general condition called “oxidative stress,” or cellular damage, and 2) broad human health concerns caused, for example, by inflammation, and DNA and protein damage. They are each implicated in different health problems – from cardiovascular disease to macular degeneration and Alzheimer’s disease and to skin damage and aging. Below we provide a brief summary of these free radicals.

The Peroxyl Radical is very important in many biological systems, including lipid peroxidation, DNA cleavage, and protein backbone modification. Hydroxyl is highly reactive and cannot be eliminated by our endogenous enzymes (such as SOD and glutathione). It can damage virtually all types of macromolecules: carbohydrates, nucleic acids, lipids, and amino acids. In the skin, hydroxyl radicals are created by UV exposure. Peroxynitrite is a reactive nitrogen species that is particularly harmful to proteins. It has been implicated in the development of certain cancers, hepatitis, and chronic inflammation. In the skin, peroxynitrite contributes to the breakdown of vital proteins, such as collagen.

Singlet Oxygen is generated in the skin by by UV. In vivo, it is linked to the oxidation of LDL cholesterol and cardiovascular disease. Singlet oxygen is highly unstable and durable. Carotenoids are very effective at scavenging singlet oxygen. Superoxide Anion is a precursor of all other reactive oxygen species and sometimes is referred to as “the mother of free radicals.” It is highly toxic and contributes to lipid and DNA damage. Antioxidants that scavenge superoxide anion also help prevent the formation of radicals such as hydrogen peroxide and hydroxyl. Superoxide anion has been linked to hypertension and cardiovascular damage.

Recently, Brunswick Labs has introduced a new test called ORAC6.0. This test expands the ORAC platform to measure the antioxidant capacity against each of the five primary reactive oxygen species mentioned above as well as Hypochlorite (HOCl) which is another important free radical that is commonly found in the body as a by-product of the metabolism of other free radicals. Direct reaction of HOCl with plasmid DNA gives rise to single- and double-strand breaks via chloramine-mediated reactions. ORAC6.0 substantially improves broad-spectrum antioxidant analysis and gives evidence of the diverse antioxidant potential of natural products against radicals other than just peroxyl.  Brunswick Labs’ research shows that the antioxidants found in a wide range of natural products are effective against these primary radicals, and that in many cases a preponderance of a product’s antioxidant capacity is described by performance against the six free radicals included to the ORAC6.0 panel.

RESULTS OF ULTIMATE PROTECTOR+ ORAC6.0 TEST

Recently [August/2019] Brunswick Labs has tested ULTIMATE PROTECTOR+™ using the new ORAC6.0 tests. The results reveal an incredible overall ORAC6.0 value of 272,743 µmole TE/gram (i.e., 272,743 per gram!). In addition, the results show that the formula offers excellent protection against all of the six types of free radicals. Specifically, the results show values of 3,376 µmole TE/gram for peroxyl radicals, 5,569 µmole TE/gram for hydroxyl radicals, 2,758 µmole TE/gram for peroxynitrite radicals, 221,866 µmole TE/gram for superoxide anion radicals, 34,169 µmole TE/gram for singlet oxygen radicals, and 5,005 µmole TE/gram for hypochlorite radicals. The table (below) shows for each free radical type the ORAC6.0 daily values for six capsules of ULTIMATE PROTECTOR+™ containing 3.55 grams of the formula.

The overall daily ORAC6.0™ value for six capsules  obtained by adding the values for each free radical type is 968,237 units (272,743 units x 3.55 g)! To the best of our knowledge there is no other product that even comes close to providing such complete protection both in terms of breadth of coverage and overall strength. The Brunswick Labs ORAC6.0™ test results for ULTIMATE PROTECTOR+™ are posted on our blog.


Ultimate Protector+ nrf2 activator formula

 

The bottom line is that you (or anyone) can stand to benefit dramatically from an advanced antioxidant formula that provides exceedingly high ORAC6.0 values and hence amazingly high cell protection…with just a modest daily dose of six small capsules. If you are at all interested to see how well this formula can protect your heath, then we suggest you try a bottle. See for yourself how ULTIMATE PROTECTOR+™ acts to provide you with the ultimate level of protection against free radicals. It’s 100% guaranteed.

ULTIMATE PROTECTOR+™ ORAC6.0 Units Per Serving (six capsules)

ORAC6.0 Units
Per Serving*

Free Radical Type
11,985 Peroxyl Radical is very important in many biological systems, including lipid peroxidation, DNA cleavage, and protein backbone modification.
19,770 Hydroxyl is highly reactive and cannot be eliminated by our endogenous enzymes. It damages virtually all types of macromolecules: carbohydrates, nucleic acids, lipids, and amino acids. In the skin, hydroxyl radicals are created by UV exposure.
9,791 Peroxynitrite is a reactive nitrogen species that is particularly harmful to proteins. It has been implicated in the development of certain cancers, hepatitis, and chronic inflammation. In the skin, peroxynitrite contributes to the breakdown of vital proteins, such as collagen.
121,300 Singlet Oxygen is generated in the skin by UV exposure. It is linked to the oxidation of LDL cholesterol and cardiovascular disease.
787,624 Superoxide Anion is a precursor of all other reactive oxygen species – sometimes referred to as “the mother of free radicals.” It is highly toxic and contributes to lipid and DNA damage.

17,768

Hypochlorite HOCl – direct reaction of HOCl with plasmid DNA gives rise to single- and double-strand breaks via chloramine-mediated reactions.

968,237

Total ORAC6.0 Per Daily Serving of Six Capsules (3.55 g)

View the Brunswick Labs Ultimate Protector™ ORAC6.0 Test Report Here

 

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ULTIMATE PROTECTOR INGREDIENTS – STRAWBERRIES

Dr. Hank Liers, PhD biography about us HPDI integratedhealth formulator founder CEO scientist physicist strawberriesUltimate Protector™ contains freeze dried strawberries, as well as components from 29 different fruits, vegetables, and herbs. Each of these ingredients contain substances that may be considered to be polyphenols, antioxidants, and Nrf2 activators. In this article I explore the ingredient strawberries, which is a component of VitaBerry Plus® from Futureceuticals.

VITABERRY PLUS®

VitaBerry® (N1023) is the trade name for a line of high ORAC blends of fruit powders and fruit extracts, exclusively available through FutureCeuticals.

VitaBerry® is a proprietary formula that combines wild bilberry and wild blueberry, cranberry, raspberry, strawberry, prune, cherry, and grape whole powders and extracts into lines of custom blends. High in fruit polyphenols, anthocyanins, proanthocyanins, ellagic acid, chlorogenic acid, resveratrol, and quinic acid, VitaBerry offers 6,000 ORAC units in a single gram.

VitaBerry® Plus (N81.3) combines the standard blend of VitaBerry® with resveratrol and quercetin to deliver a minimum of 12,000 ORAC units per gram.

Strawberry strawberries

HEALTH BENEFITS OF STRAWBERRIES

Strawberries long have grown wild in the world’s temperate regions. They have been cultivated for several thousand years and were prized among the ancient Romans. Most of the common varieties of strawberry derive from a hybrid (Frangaria x ananassa). Strawberries have an ORAC value of 1,540, which is very high among the fruits and vegetables tested by the USDA. They are a good source of vitamins C, K, B2, B5, B6, and folate. They also contain appreciable amounts of the minerals manganese, iodine, and potassium, as well as dietary fiber.

Like other berries, the antioxidants contained in strawberries may be useful against diseases of the heart and arteries by preventing the oxidation of lipids. The phytonutrient phenols most abundant in strawberries are anthocyanins and ellagitannins. The anthocyanins help to prevent oxidative damage from free radicals in body. The unique phenol profile of the strawberry enables it not only to protect the heart, but also to fight inflammation. Studies have shown that strawberries also protect the brain from oxidative stress and may therefore reduce age-related cognitive decline in brain function. Strawberries have been shown to be Nrf2 activators that can stimulate the endogenous production of protective enzymes in the body.

Here is a list of the antioxidant and anti-inflammatory phytonutrients in found in strawberries.

  • Anthocyanins
    • cyanidins
    • pelargonidins
  • Flavonols
    • procyanidins
    • catechins
    • gallocatechins
    • epicatechins
    • kaempferol
    • quercetin
  • Hydroxy-benzoic acids
    • ellagic acid
    • gallic acid
    • vanillic acid*
    • salicylic acid
  • Hydroxy-cinnamic acids
    • cinnamic acid
    • coumaric acid
    • caffeic acid
    • ferulic acid
  • Tannins
    • ellagitannins
    • gallotannins
  • Stilbenes
    • resveratrol

For more information on strawberries visit: http://www.whfoods.com/genpage.php?tname=foodspice&dbid=32

Scientific Studies on the Antioxidant Effects of Strawberries

Below, I provide relevant scientific studies on the antioxidant effects and potential health benefits of strawberries.

Strawberry as a functional food: an evidence-based review

From: http://www.ncbi.nlm.nih.gov/pubmed/24345049

Abstract

Emerging research provides substantial evidence to classify strawberries as a functional food with several preventive and therapeutic health benefits. Strawberries, a rich source of phytochemicals (ellagic acid, anthocyanins, quercetin, and catechin) and vitamins (ascorbic acid and folic acid), have been highly ranked among dietary sources of polyphenols and antioxidant capacity. It should however be noted that these bioactive factors can be significantly affected by differences in strawberry cultivars, agricultural practices, storage, and processing methods: freezing versus dry heat has been associated with maximum retention of strawberry bioactives in several studies. Nutritional epidemiology shows inverse association between strawberry consumption and incidence of hypertension or serum C-reactive protein; controlled feeding studies have identified the ability of strawberries to attenuate high-fat diet induced postprandial oxidative stress and inflammation, or postprandial hyperglycemia, or hyperlipidemia in subjects with cardiovascular risk factors. Mechanistic studies have elucidated specific biochemical pathways that might confer these protective effects of strawberries: upregulation of endothelial nitric oxide synthase (eNOS) activity, downregulation of NF-kB activity and subsequent inflammation, or inhibitions of carbohydrate digestive enzymes. These health effects may be attributed to the synergistic effects of nutrients and phytochemicals in strawberries. Further studies are needed to define the optimal dose and duration of strawberry intake in affecting levels of biomarkers or pathways related to chronic diseases.

Bioactive Compounds and Antioxidant Activity in Different Types of Berries

Abstract

Berries, especially members of several families, such as Rosaceae (strawberry, raspberry, blackberry), and Ericaceae (blueberry, cranberry), belong to the best dietary sources of bioactive compounds (BAC). They have delicious taste and flavor, have economic importance, and because of the antioxidant properties of BAC, they are of great interest also for nutritionists and food technologists due to the opportunity to use BAC as functional foods ingredients. The bioactive compounds in berries contain mainly phenolic compounds (phenolic acids, flavonoids, such as anthocyanins and flavonols, and tannins) and ascorbic acid. These compounds, either individually or combined, are responsible for various health benefits of berries, such as prevention of inflammation disorders, cardiovascular diseases, or protective effects to lower the risk of various cancers. In this review bioactive compounds of commonly consumed berries are described, as well as the factors influencing their antioxidant capacity and their health benefits.

Dietary intakes of berries and flavonoids in relation to cognitive decline

From: http://www.ncbi.nlm.nih.gov/pubmed/22535616

Abstract

Objective: Berries are high in flavonoids, especially anthocyanidins, and improve cognition in experimental studies. We prospectively evaluated whether greater long-term intakes of berries and flavonoids are associated with slower rates of cognitive decline in older women.

Methods: Beginning in 1980, a semiquantitative food frequency questionnaire was administered every 4 years to Nurses’ Health Study participants. In 1995–2001, we began measuring cognitive function in 16,010 participants, aged ≥70 years; follow-up assessments were conducted twice, at 2-year intervals. To ascertain long-term diet, we averaged dietary variables from 1980 through the initial cognitive interview. Using multivariate-adjusted, mixed linear regression, we estimated mean differences in slopes of cognitive decline by long-term berry and flavonoid intakes.

Results: Greater intakes of blueberries and strawberries were associated with slower rates of cognitive decline (eg, for a global score averaging all 6 cognitive tests, for blueberries: p-trend = 0.014 and mean difference = 0.04, 95% confidence interval [CI] = 0.01–0.07, comparing extreme categories of intake; for strawberries: p-trend = 0.022 and mean difference = 0.03, 95% CI = 0.00–0.06, comparing extreme categories of intake), after adjusting for multiple potential confounders. These effect estimates were equivalent to those we found for approximately 1.5 to 2.5 years of age in our cohort, indicating that berry intake appears to delay cognitive aging by up to 2.5 years. Additionally, in further supporting evidence, greater intakes of anthocyanidins and total flavonoids were associated with slower rates of cognitive decline (p-trends = 0.015 and 0.053, respectively, for the global score).

Interpretation: Higher intake of flavonoids, particularly from berries, appears to reduce rates of cognitive decline in older adults.

Addition of strawberries to the usual diet decreases resting chemiluminescence of fasting blood in healthy subjects-possible health-promoting effect of these fruits consumption

From: http://www.ncbi.nlm.nih.gov/pubmed/24912053

Abstract

OBJECTIVE: Regular strawberry consumption augmented plasma antioxidant activity and decreased lipid peroxidation suggests preventive potential of these fruits against oxidative stress-dependent disorders. Blood phagocytes are important source of oxidants that may contribute to systemic oxidative stress. We examined the effect of strawberry consumption on the luminol enhanced whole blood chemiluminescence (LBCL) reflecting oxidants generation by circulating phagocytes in healthy subjects.

METHODS: Thirty-one healthy subjects (being on their usual diet) consumed 500 g of strawberry pulp daily (between 11.00-14.00) for 30 days (1st strawberry course) and after 10 day wash-out the cycle was repeated (2nd strawberry course). Fasting blood and spot morning urine samples were collected before and after each strawberry course for measuring resting and agonist (fMLP)-induced LBCL, various phenolics and plasma antioxidant activity. Twenty subjects served as a control in respect to LBCL changes over the study period.

RESULTS: Strawberry consumption decreased median resting LBCL and this effect was more evident after the 1st course (by 38.2%, p < 0.05) than after the the 2nd one (18.7%), while fMLP-induced LBCL was constant. No changes in LBCL were noted in controls. Strawberries increased fasting plasma levels of caffeic acid and homovanillic acid as well as urolithin A and 4-hydroxyhippuric acid in spot urine. Plasma antioxidant activity and the number of circulating phagocytes did not change over the study period. Resting LBCL correlated positively with the number of circulating polymorphonuclear leukocytes at all occasions and negative correlation with plasma 4-hydroxyhippuric acid was noted especially after the first strawberry course (r = -0.46, p < 0.05).

CONCLUSIONS: The decrease in resting LBCL suggests that regular strawberry consumption may suppress baseline formation of oxidants by circulating phagocytes. This may decrease the risk of systemic imbalance between oxidants and anti-oxidants and be one of mechanisms of health-promoting effect of these fruits consumption.

Consumption of strawberries on a daily basis increases the non-urate 2,2-diphenyl-1-picryl-hydrazyl (DPPH) radical scavenging activity of fasting plasma in healthy subjects

From: http://www.ncbi.nlm.nih.gov/pubmed/25120279

Abstract

Strawberries contain anthocyanins and ellagitanins which have antioxidant properties. We determined whether the consumption of strawberries increase the plasma antioxidant activity measured as the ability to decompose 2,2-diphenyl-1-picrylhydrazyl radical (DPPH) in healthy subjects. The study involved 10 volunteers (age 41 ± 6 years, body weight 74.4 ± 12.7 kg) that consumed 500 g of strawberries daily for 9 days and 7 matched controls. Fasting plasma and spot morning urine samples were collected at baseline, during fruit consumption and after a 6 day wash-out period. DPPH decomposition was measured in both deproteinized native plasma specimens and pretreated with uricase (non-urate plasma). Twelve phenolics were determined with HPLC. Strawberries had no effect on the antioxidant activity of native plasma and circulating phenolics. Non-urate plasma DPPH decomposition increased from 5.7 ± 0.6% to 6.6 ± 0.6%, 6.5 ± 1.0% and 6.3 ± 1.4% after 3, 6 and 9 days of supplementation, respectively. The wash-out period reversed this activity back to 5.7 ± 0.8% (p<0.01). Control subjects did not reveal any changes of plasma antioxidant activity. Significant increase in urinary urolithin A and 4-hydroxyhippuric (by 8.7- and 5.9-times after 6 days of supplementation with fruits) was noted. Strawberry consumption can increase the non-urate plasma antioxidant activity which, in turn, may decrease the risk of systemic oxidants overactivity.

One-month strawberry-rich anthocyanin supplementation ameliorates cardiovascular risk, oxidative stress markers and platelet activation in humans

From: http://www.ncbi.nlm.nih.gov/pubmed/24406274

Abstract

Strawberries are an important fruit in the Mediterranean diet because of their high content of essential nutrients and beneficial phytochemicals, which seem to exert beneficial effects in human health. Healthy volunteers were supplemented daily with 500 g of strawberries for 1 month. Plasma lipid profile, circulating and cellular markers of antioxidant status, oxidative stress and platelet function were evaluated at baseline, after 30 days of strawberry consumption and 15 days after the end of the study. A high concentration of vitamin C and anthocyanins was found in the fruits. Strawberry consumption beneficially influenced the lipid profile by significantly reducing total cholesterol, low-density lipoprotein cholesterol and triglycerides levels (-8.78%, -13.72% and -20.80%, respectively; P<.05) compared with baseline period, while high-density lipoprotein cholesterol remained unchanged. Strawberry supplementation also significant decreased serum malondialdehyde, urinary 8-OHdG and isoprostanes levels (-31.40%, -29.67%, -27.90%, respectively; P<.05). All the parameters returned to baseline values after the washout period. A significant increase in plasma total antioxidant capacity measured by both ferric reducing ability of plasma and oxygen radical absorbance capacity assays and vitamin C levels (+24.97%, +41.18%, +41.36%, respectively; P<.05) was observed after strawberry consumption. Moreover, the spontaneous and oxidative hemolysis were significant reduced (-31.7% and -39.03%, respectively; P<.05), compared to the baseline point, which remained stable after the washout period. Finally, strawberry intake significant decrease (P<.05) the number of activated platelets, compared to both baseline and washout values. Strawberries consumption improves plasma lipids profile, biomarkers of antioxidant status, antihemolytic defenses and platelet function in healthy subjects, encouraging further evaluation on a population with higher cardiovascular disease risk.

Impact of strawberries on human health: insight into marginally discussed bioactive compounds for the Mediterranean diet

Abstract

OBJECTIVE: To review and update the current knowledge on the potential impact of strawberry on human health, with particular attention on compounds and indirect mechanisms of action not exhaustively considered.

DESIGN: Personal perspectives and recent data.

SETTING: International.

RESULTS: Our research group was among the few groups that have recently investigated the folate content in fresh, stored and processed strawberries, and the data look very promising. As well, some in vivo evidence of the impact of strawberry intake on the folate status in humans have already been reported, but a new increasing interest on this field is strongly hoped. Furthermore, the hypouricaemic effects previously ascribed to cherry consumption need to be evaluated in respect to strawberry intake. At the moment, inconsistent results come from the few investigations designed at this proposal. In our studies, a great interindividual variability was observed on plasma urate levels in response to strawberry intake, suggesting a putative effect.

CONCLUSIONS: The mechanisms responsible for the potential health-promoting effects of strawberry may not be necessarily searched in the activity of phytochemicals. Particularly, a greater interest should be addressed to show whether a prolonged strawberry consumption may effectively improve the folate status and reduce the incidence of folate-related pathological conditions. Furthermore, the hypouricaemic effects of cherries need to be evaluated also in respect to strawberry intake, and the mechanisms of actions and anti-gout potentialities need to be studied in detail. Future investigations involving human trials should be aimed at following these underestimated scientific tracks.

strawberry strawberries fruit

SUMMARY

Strawberries are an important fruit full of polyphenols, anthocyanins, antioxidants, and Nrf2 activators that help to make Ultimate Protector such an outstanding nutritional supplement.

 

Contact Us:

You can reach HPDI by calling 1-800-228-4265, email support(at)IntegratedHealth.com, or visit the retail website: www.IntegratedHealth.com

Health care professionals and retailers can apply for wholesale account, which includes access to the HPDI reseller website: www.HealthProductsDistributors.com

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ULTIMATE PROTECTOR INGREDIENTS – BLACK CURRANT EXTRACT

Dr. Hank Liers, PhD biography HPDI integratedhealth formulator scientist physicist black currant extractUltimate Protector contains black currant extract, as well as components from 29 different fruits, vegetables, and herbs. Each of these ingredients contain substances that may be considered to be polyphenols, antioxidants, and Nrf2 activators. In this article I will explore the ingredient black currant extract, which is a component of Anthocomplete™ from Futureceuticals.

ANTHOCOMPLETE™

AnthoComplete™ (N669) is a specially designed blend of anthocyanins derived from wild bilberry and wild blueberry, açaí, black currant extract, sweet cherry, raspberry, elderberry, blackberry, aronia, black soybean hull extract, and blue corn. Anthocyanins are powerful plant polyphenols associated with a variety of areas of human health, including healthy aging, healthy glucose metabolism, cardiovascular health, and inflammation management.

Carefully designed to maximize the amount of beneficial anthocyanins that can be available in a single source, AnthoComplete™ is a proprietary formula suitable for a wide range of applications.

With its diverse blend, AnthoComplete™ contains a minimum level of 10% anthocyanins, 3,000 ORAC μmole TE/g (typical), and 15% total phenolics (typical).

Owing to the high levels of anthocyanins and vitamin C, two types of important antioxidants, black currants have been shown by scientific research to have many benefits in promoting health and wellness. Vitamin C is an essential nutrient required for the body’s normal functions and the antioxidant polyphenols in black currants (particularly anthocyanins) may help in maintaining cardiovascular health, aging and brain health, urinary tract health, and healthy vision.

Black Currant

Black Currant Berries

HEALTH BENEFITS OF BLACK CURRANT EXTRACT

Black currants (Ribes nigrum) have been used in a wide variety of foods for many years. They contain a relatively large vitamin C content, more than almost any other commonly consumed fruit. Ongoing research is further showing the benefits of black currants based largely on the polyphenolic content of the fruit and its related products.

Black currants have antioxidant value (oxygen radical absorbance capacity – ORAC) of 7950 Trolex Equivalents per 100 g, which is one of the highest value for fruits after chokeberries, elderberry, and cranberries.

The intensely dark color of blackcurrants is due to its high content of anthocyanin — primarily 3-glucosides and 3-rutinosides of cyanidin and delphinidin. It has been found that these components exhibit powerful hydroxyl radical scavenging abilities and protect endothelial cells in model systems.

In addition, the anthocyanins have been shown to positively influence the α-glucosidase phase of starch digestion providing a reduction of sugar release during starch food digestion.

Also, black currants are a good source of glycosylated flavonols such as quercetin, myrecetin and kaempferol. Scientific studies at the fundamental cellular level have indicated that these compounds can interact with the bodies own innate Antioxidant Response Elements (ARE), such as the transcription factor Nrf2, and more specifically stimulate expression of the detoxification enzymes such as NAD(P)H:quinone oxidoreductase, glutathione S-transferase, and uridine diphosphate-glucuronosyltransferase isoenzymes.

SCIENTIFIC STUDIES ON THE ANTIOXIDANT EFFECTS OF BLACK CURRANTS

Below, we provide a few relevant scientific studies on the antioxidant effects and potential health benefits of black currant extracts.

Biological activity of blackcurrant extracts (Ribes nigrum L.) in relation to erythrocyte membranes.
From: http://www.ncbi.nlm.nih.gov/pubmed/24527456

Abstract

Compounds contained in fruits and leaves of blackcurrant (Ribes nigrum L.) are known as agents acting preventively and therapeutically on the organism. The HPLC analysis showed they are rich in polyphenol anthocyanins in fruits and flavonoids in leaves, that have antioxidant activity and are beneficial for health. The aim of the research was to determine the effect of blackcurrant fruit and leaf extracts on the physical properties of the erythrocyte membranes and assess their antioxidant properties. The effect of the extracts on osmotic resistance, shape of erythrocytes and hemolytic and antioxidant activity of the extracts were examined with spectrophotometric methods. The FTIR investigation showed that extracts modify the erythrocyte membrane and protect it against free radicals induced by UV radiation. The results show that the extracts do not induce hemolysis and even protect erythrocytes against the harmful action of UVC radiation, while slightly strengthening the membrane and inducing echinocytes. The compounds contained in the extracts do not penetrate into the hydrophobic region, but bind to the membrane surface inducing small changes in the packing arrangement of the polar head groups of membrane lipids. The extracts have a high antioxidant activity. Their presence on the surface of the erythrocyte membrane entails protection against free radicals.

 

Anthocyanin-rich black currant extract suppresses the growth of human hepatocellular carcinoma cells.

Abstract

Dietary antioxidants, such as anthocyanins, are helpful in the prevention and control of various diseases by counteracting the imbalance of oxidative and antioxidative factors in the living systems. Black currant (Ribes nigrum L., Grossulariaceae) is known to contain high amounts of anthocyanins (250 mg/100 g fresh fruit). Black currant fruits have been used in Asian and European traditional medicine for the treatment of a variety of diseases. Black currant extract has recently been found to be the second most effective amongst nine different berry extracts studied for their free radical scavenging activity. Constituents present in black currant juice have been found to exert a number of health-promoting effects, including immunomodulatory, antimicrobial and antiinflammatory actions, inhibition of low-density lipoprotein, and reduction of cardiovascular diseases. Although antioxidant and antiinflammatory effects of black currant juice could be of value in preventing and treating oxidative stress- and inflammation-driven cancers, no experimental evidence is available to now. The objective of the present study was to evaluate the potential antiproliferative effects of black currant fruit skin extract against HepG2 human liver cancer cells. The aqueous extract yielded an anthocyanin-rich fraction with cyanidin-3-O-rutinoside as one of the major anthocyanins. This fraction exhibited a potent cytotoxic effect on HepG2 cells and this effect was more pronounced than that of delphinidin and cyanidin, two major aglycones of anthocyanins present in black currant. Our results indicate, for the first time, that black currant skin containing an anthocyanin-rich fraction inhibits the proliferation of liver cancer cells, possibly due to additive as well as synergistic effects. This product could be useful in the prevention and treatment of human hepatocellular carcinoma.

 

Black currant anthocyanins abrogate oxidative stress through Nrf2-mediated antioxidant mechanisms in a rat model of hepatocellular carcinoma.

Abstract

Hepatocellular carcinoma (HCC), considered to be one of the most lethal cancers with almost > 1 million deaths reported annually worldwide, remains a devastating disease with no known effective cure. Hence, chemopreventive strategies come into play, offering an effective and safe mode of treatment, ideal to ward off potential cancer risks and mortality. A major predisposing condition, pertinent to the development and progression of HCC is oxidative stress. We previously reported a striking chemopreventive effect of anthocyanin-rich black currant skin extract (BCSE) against diethylnitrosamine (DENA)-initiated hepatocarcinogenesis in rats. The current study aims to elucidate the underlying antioxidant mechanisms of black currant anthocyanins implicated in the previously observed chemopreventive effects against experimental hepatocarcinogenesis. Dietary BCSE (100 and 500 mg/kg) administered four weeks before and 18 weeks after DENA challenge decreased abnormal lipid peroxidation, protein oxidation, and expression of inducible nitric oxide synthase (iNOS) and 3-nitrotyrosine (3-NT) in a dose-responsive fashion. Mechanistic studies revealed that BCSE upregulated the gene expression of a number of hepatic antioxidant and carcinogen detoxifying enzymes, such as NAD(P)H:quinone oxidoreductase, glutathione S-transferase, and uridine diphosphate-glucuronosyltransferase isoenzymes, in DENA-initiated animals. Protein and mRNA expressions of nuclear factor E2-related factor 2 (Nrf2) were substantially elevated with BCSE treatment, providing a direct evidence of a coordinated activation of the Nrf2-regulated antioxidant pathway, which led to the upregulation of a variety of housekeeping genes. The results of our study provide substantial evidence that black currant bioactive anthocyanins exert chemopreventive actions against DENA-inflicted hepatocarcinogenesis by attenuating oxidative stress through activation of Nrf2 signaling pathway.

 

Black currant phytoconstituents exert chemoprevention of diethylnitrosamine-initiated hepatocarcinogenesis by suppression of the inflammatory response.

From: http://www.ncbi.nlm.nih.gov/pubmed/22213170

Abstract

Black currant fruits containing high amounts of anthocyanins are known to possess potent antioxidant and anti-inflammatory properties. We have previously reported that anthocyanin-rich black currant skin extract (BCSE) inhibits diethylnitrosamine (DENA)-initiated hepatocarcinogenesis in rats although the underlying mechanisms are not fully understood. Our present study investigates the anti-inflammatory mechanisms of BCSE during DENA rat liver carcinogenesis. Dietary BCSE (100 or 500 mg/kg) treatment for 22 wk afforded a striking inhibition of DENA-induced hepatic gamma-glutamyl transpeptidase-positive preneoplastic foci in a dose-responsive fashion. There was a significant increase in hepatic expression of heat shock proteins (HSP70 and HSP90), cyclooxygenase-2, and nuclear factor-κB (NF-κB) in DENA-exposed rat livers. Dietary BCSE dose-dependently abrogated all these elevated inflammatory markers. The possible cardiotoxicity of BCSE was assessed by monitoring cardiac functions using transthoracic echocardiography. BCSE-mediated anti-inflammatory effects during rat liver carcinogenesis have been achieved without any cardiotoxicity. Our results provide convincing evidence, for the very first time, that suppression of the inflammatory cascade through modulation of the NF-κB signaling pathway could be implicated, at least in part, in the chemopreventive effects of black currant bioactive phytoconstituents against experimental hepatocarcinogenesis. These results coupled with an excellent safety profile of BCSE support the development of black currant phytochemicals for the chemoprevention of inflammation-driven hepatocellular cancer.

 

Anthocyanin-rich black currant (Ribes nigrum L.) extract affords chemoprevention against diethylnitrosamine-induced hepatocellular carcinogenesis in rats.

Abstract

Anthocyanins are known to possess potent anticarcinogenic properties against several cancers thus demonstrating potential for cancer prevention. Black currant (Ribes nigrum L., Grossulariaceae) fruits have a high anthocyanin content. This “superfruit” is known to possess various pharmacological effects including alleviation of chronic oxidative stress and inflammation. In contrast to a large volume of literature on the health benefits of black currant, limited evidence on antitumor effects of black currant exists with virtually no data on the prevention of experimental carcinogenesis. In the current study, we have investigated the chemopreventive effects of an anthocyanin-rich black currant skin extract (BCSE) utilizing our well-characterized model of rat liver carcinogenesis. Initiation of hepatocarcinogenesis was done by intraperitoneal injection of diethylnitrosamine (DENA) followed by promotion with phenobarbital. The rats were exposed to dietary BCSE for 4 weeks prior to initiation, and the treatment was continued for 22 consecutive weeks. BCSE dose-dependently decreased the incidence, total number, multiplicity, size and volume of preneoplastic hepatic nodules. The antihepatocarcinogenic effect of BCSE was confirmed by histopathological examination of liver sections. Immunohistochemical analysis of proliferating cell nuclear antigen and DNA fragmentation revealed BCSE-mediated inhibition of abnormal cell proliferation and induction of apoptosis in DENA-induced rat liver tumorigenesis respectively. Mechanistic studies revealed that BCSE-mediated proapototic signal during experimental hepatocarcinogenesis may be propagated via the up-regulation of Bax and down-regulation of Bcl-2 expression at the translational level. These results along with a safety profile of BCSE encourage the development of black currant bioactive constituents as chemopreventive agents for human liver cancer.

 

Purified Anthocyanins from Bilberry and Black Currant Attenuate Hepatic Mitochondrial Dysfunction and Steatohepatitis in Mice with Methionine and Choline Deficiency

Abstract

Abstract Image

The berries of bilberry and black currant are a rich source of anthocyanins, which are thought to have favorable effects on nonalcoholic steatohepatitis (NASH). This study was designed to examine whether purified anthocyanins from bilberry and black currant are able to limit the disorders related to NASH induced by a methionine-choline-deficient (MCD) diet in mice. The results showed that treatment with anthocyanins not only alleviated inflammation, oxidative stress, steatosis, and even fibrosis but also improved depletion of mitochondrial content and damage of mitochondrial biogenesis and electron transfer chain developed concomitantly in the liver of mice fed the MCD diet. Furthermore, anthocyanins treatment promoted activation of AMP-activated protein kinase (AMPK) and expression of peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α). These data provide evidence that anthocyanins possess significant protective effects against NASH and mitochondrial defects in response to a MCD diet, with a mechanism maybe through affecting the AMPK/PGC-1α signaling pathways.

SUMMARY

Black currants are an important fruit full of polyphenols, anthocyanins, antioxidants, and Nrf2 activators that help to make Ultimate Protector such an outstanding nutritional supplement.

 

 

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ULTIMATE PROTECTOR INGREDIENTS – WILD BILBERRY AND WILD BLUEBERRY

Dr. Hank Liers, PhD biography about us HPDI integratedhealth formulator founder CEO scientist physicist wild bilberry and wild blueberry

Ultimate Protector contains wild bilberry and wild blueberry, as well as components from 29 different fruits, vegetables, and herbs. Each of these ingredients contain substances that may be considered to be polyphenols, antioxidants, and Nrf2 activators. In this article I will explore the ingredients wild bilberry and wild blueberry, which are components of Anthocomplete™ and VitaBerry Plus® from Futureceuticals.

ANTHOCOMPLETE™

AnthoComplete™ (N669) is a specially designed blend of anthocyanins derived from wild bilberry and wild blueberry, acai, black currant extract, sweet cherry, raspberry, elderberry, blackberry, aronia, black soybean hull extract, and blue corn. Anthocyanins are powerful plant polyphenols associated with a variety of areas of human health, including healthy aging, healthy glucose metabolism, cardiovascular health, and inflammation management.

Carefully designed to maximize the amount of beneficial anthocyanins that can be available in a single source, AnthoComplete is a proprietary formula suitable for a wide-range of applications.

With its diverse blend, AnthoComplete contains a minimum level of 10% anthocyanins, 3,000 ORAC μmole TE/g (typical), and 15% total phenolics (typical).

Bilberry / Blueberry wild bilberry and wild bluebery

VITABERRY PLUS®

VitaBerry® (N1023) is the trade name for a line of high ORAC blends of fruit powders and fruit extracts, exclusively available through FutureCeuticals.

VitaBerry® is a proprietary formula that combines wild bilberry and wild blueberry, cranberry, raspberry, strawberry, prune, cherry, and grape whole powders and extracts into lines of custom blends. High in fruit polyphenols, anthocyanins, proanthocyanins, ellagic acid, chlorogenic acid, resveratrol, and quinic acid, VitaBerry offers 6,000 ORAC units in a single gram.

VitaBerry® Plus (N81.3) combines the standard blend of VitaBerry® with resveratrol and quercetin to deliver a minimum of 12,000 ORAC units per gram.

HEALTH BENEFITS OF WILD BILBERRY AND WILD BLUEBERRY

Bilberry is any of several Eurasian  species of low-growing shrubs in the genus Vaccinium, bearing edible, nearly black berries. The species most often referred to is Vaccinium myrtillus L., but there are several other closely related species. Bilberries are distinct from blueberries but closely related. Whereas the bilberry is native to Europe, the blueberry is native to North America.

The bilberry fruit is smaller than that of the blueberry, but with a fuller taste. Bilberries are darker in color, and usually appear near black with a slight shade of purple. While blueberry fruit pulp is light green in color, bilberry is red or purple, heavily staining the fingers, lips, and tongue of consumers eating the raw fruit. The color comes from diverse anthocyanins.

So-called wild (lowbush) blueberries, smaller than cultivated highbush ones, are prized for their intense color. “Wild” has been adopted as a marketing term for harvests of managed native stands of lowbush blueberries. The bushes are not planted or genetically manipulated, but they are pruned or burned every two years, and pests are “managed”. The content of polyphenols and anthocyanins in lowbush (wild) blueberries (V. angustifolium) exceeds values found in highbush cultivars.

wild bilberry and wild blueberry

Wild bilberry and wild blueberry (above) provide Nrf2 activators.

The key compounds in bilberry fruit are called anthocyanins and anthocyanosides. These compounds help build strong blood vessels and improve circulation to all areas of the body. They also prevent blood platelets from clumping together (helping to reduce the risk of blood clots), and they have antioxidant properties (preventing or reducing damage to cells from free radicals). Anthocyanins boost the production of rhodopsin, a pigment that improves night vision and helps the eye adapt to light changes.

Bilberry fruit is also rich in tannins, a substance that acts as an astringent. The tannins have anti-inflammatory properties and may help control diarrhea.

Bilberries have been shown to have the highest Oxygen Radical Absorbance Capacity (ORAC) rating of more than 20 fresh fruits and berries. The antioxidant properties of bilberries were shown to be even stronger than those of cranberries, raspberries, strawberries, plums, or cultivated blueberries.

The antioxidant powers and health benefits of bilberries and blueberries can be attributed to a number of remarkable compounds contained in them, including the following:

  • Anthocyanins
    • malvidins
    • delphinidins
    • pelargonidins
    • cyanidins
    • peonidins
  • Hydroxycinnamic acids
    • caffeic acids
    • ferulic acids
    • coumaric acids
  • Hydroxybenzoic acids
    • gallic acids
    • procatchuic acids
  • Flavonols
    • kaempferol
    • quercetin
    • myricetin
  • Other phenol-related phytonutrients
    • pterostilbene
    • resveratrol
  • Other nutrients
    • lutein
    • zeaxanthin
    • Vitamin K
    • Vitamin C
    • manganese

Scientific Studies on the Antioxidant Effects of Wild Bilberry and Wild Blueberry

Databases of scientific studies (like the National Institutes of Health (NIH) PubMed database) contain thousands of up-to-date studies and abstracts about various Vaccinium species, including wild bilberry and wild blueberry (V. myrtillis and V. angustfolium, respectively).

We provide a few relevant scientific studies on the antioxidant effects of wild bilberry and wild blueberry.

In vitro anticancer activity of fruit extracts from Vaccinium species.

From: http://www.ncbi.nlm.nih.gov/pubmed/8693031

Abstract

Fruit extracts of four Vaccinium species (lowbush blueberry, bilberry, cranberry, and lingonberry) were screened for anticarcinogenic compounds by a combination of fractionation and in vitro testing of their ability to induce the Phase II xenobiotic detoxification enzyme quinone reductase (QR) and to inhibit the induction of ornithine decarboxylase (ODC), the rate-limiting enzyme in polyamine synthesis, by the tumor promoter phorbol 12-myristate 13-acetate (TPA). The crude extracts, anthocyanin and proanthocyanidin fractions were not highly active in QR induction whereas the ethyl acetate extracts were active QR inducers. The concentrations required to double QR activity (designated CDqr) for the ethyl acetate extracts of lowbush blueberry, cranberry, lingonberry, and bilberry were 4.2, 3.7, 1.3, and 1.0 microgram tannic acid equivalents (TAE), respectively, Further fractionation of the bilberry ethyl acetate extract revealed that the majority of inducer potency was contained in a hexane/chloroform subfraction (CDqr = 0.07 microgram TAE). In contrast to their effects on QR, crude extracts of lowbush blueberry, cranberry, and lingonberry were active inhibitors of ODC activity. The concentrations of these crude extracts needed to inhibit ODC activity by 50% (designated IC50) were 8.0, 7.0, and 9.0 micrograms TAE, respectively. The greatest activity in these extracts appeared to be contained in the polymeric proanthocyanidin fractions of the lowbush blueberry, cranberry, and lingonberry fruits (IC50 = 3.0, 6.0, and 5.0 micrograms TAE, respectively). The anthocyanidin and ethyl acetate extracts of the four Vaccinium species were either inactive or relatively weak inhibitors of ODC activity. Thus, components of the hexane/chloroform fraction of bilberry and of the proanthocyanidin fraction of lowbush blueberry, cranberry, and lingonberry exhibit potential anticarcinogenic activity as evaluated by in vitro screening tests.

 

Bilberry (Vaccinium myrtillus) anthocyanins modulate heme oxygenase-1 and glutathione S-transferase-pi expression in ARPE-19 cells.

From: http://www.ncbi.nlm.nih.gov/pubmed/17460300

Abstract

PURPOSE: To determine whether anthocyanin-enriched bilberry extracts modulate pre- or posttranslational levels of oxidative stress defense enzymes heme-oxygenase (HO)-1 and glutathione S-transferase-pi (GST-pi) in cultured human retinal pigment epithelial (RPE) cells.

METHODS: Confluent ARPE-19 cells were preincubated with anthocyanin and nonanthocyanin phenolic fractions of a 25% enriched extract of bilberry (10(-6)-1.0 mg/mL) and, after phenolic removal, cells were oxidatively challenged with H(2)O(2). The concentration of intracellular glutathione was measured by HPLC and free radical production determined by the dichlorofluorescin diacetate assay. HO-1 and GST-pi protein and mRNA levels were determined by Western blot and RT-PCR, respectively.

RESULTS: Preincubation with bilberry extract ameliorated the intracellular increase of H(2)O(2)-induced free radicals in RPE, though H(2)O(2) cytotoxicity was not affected. By 4 hours, the extract had upregulated HO-1 and GST-pi protein by 2.8- and 2.5-fold, respectively, and mRNA by 5.5- and 7.1-fold, respectively, in a dose-dependent manner. Anthocyanin and nonanthocyanin phenolic fractions contributed similarly to mRNA upregulation.

CONCLUSIONS: Anthocyanins and other phenolics from bilberry upregulate the oxidative stress defense enzymes HO-1 and GST-pi in RPE, suggesting that they stimulate signal transduction pathways influencing genes controlled by the antioxidant response element.

 

Berry anthocyanins suppress the expression and secretion of proinflammatory mediators in macrophages by inhibiting nuclear translocation of NF-κB independent of NRF2-mediated mechanism.

From: http://www.ncbi.nlm.nih.gov/pubmed/24565673

Abstract

The objectives of this study were to compare the anti-inflammatory effects of anthocyanins from blueberry (BBA), blackberry (BKA), and blackcurrant (BCA) and to determine the relationship between their antioxidant capacity and anti-inflammatory effect in macrophages. Major anthocyanins in BBA, BKA and BCA were malvidin-3-glucoside (16%), cyanidin-3-glucoside (98%) and delphinidin-3-rutinoside (44%), respectively. BKA showed higher total antioxidant capacity than BBA and BCA. RAW 264.7 macrophages were incubated with 0-20 μg/ml of BBA, BKA and BCA, and subsequently activated by lipopolysaccharide (LPS) to measure proinflammatory cytokine production. Interleukin 1β (IL-1β) messenger RNA (mRNA) levels were significantly decreased by all berry anthocyanins at 10 μg/ml or higher. Tumor necrosis factor α (TNFα) mRNA levels and secretion were also significantly decreased in LPS-treated macrophages. The levels of the repression were comparable for all berry anthocyanins. LPS-induced nuclear factor κB (NF-κB) p65 translocation to the nucleus was markedly attenuated by all of the berry anthocyanins. In bone marrow-derived macrophages (BMMs) from nuclear factor E2-related factor 2 wild-type (Nrf2(+/+)) mice, BBA, BKA and BCA significantly decreased cellular reactive oxygen species (ROS) levels with a concomitant decrease in IL-1β mRNA levels upon LPS stimulation. However, in the BMM from Nrf2(-/-) mice, the anthocyanin fractions were able to significantly decrease IL-1β mRNA despite the fact that ROS levels were not significantly affected. In conclusion, BBA, BKA and BCA exert their anti-inflammatory effects in macrophages, at least in part, by inhibiting nuclear translocation of NF-κB independent of the NRF2-mediated pathways.

 

Purified Anthocyanins from Bilberry and Black Currant Attenuate Hepatic Mitochondrial Dysfunction and Steatohepatitis in Mice with Methionine and Choline Deficiency

From: http://pubs.acs.org/doi/abs/10.1021/jf504926n

Abstract

The berries of bilberry and black currant are rich source of anthocyanins, which are thought to have favorable effects on non-alcoholic steatohepatitis (NASH). This study was designed to examine whether purified anthocyanins from bilberry and black currant are able to limit the disorders related to NASH induced by a methionine-choline-deficient (MCD) diet in mice. The results showed that treatment with anthocyanins not only alleviated inflammation, oxidative stress, steatosis and even fibrosis, but also improved the depletion of mitochondrial content and damage of mitochondrial biogenesis and electron transfer chain developed concomitantly in the liver of mice fed the MCD diet. Furthermore, anthocyanins treatment promoted activation of AMP-activated protein kinase (AMPK) and expression of peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α). These data provide evidence that anthocyanins possess significant protective effects against NASH and mitochondrial defects in response to a MCD diet, with mechanism maybe through affecting the AMPK/PGC-1α signaling pathways.

 

Effect of blueberry on hepatic and immunological functions in mice.

From: http://www.ncbi.nlm.nih.gov/pubmed/20382588

Abstract

Background: Conventional drugs used in the treatment and prevention of liver diseases often have side effects, therefore research into natural substances are of significance. This study examined the effects of blueberry on liver protection and cellular immune functions.

METHODS: To determine the effects of blueberry on liver protective function, male mice were orally administered blueberry (0.6 g/10 g) or normal saline for 21 days. Hepatic RNA was extracted by Trizol reagent, and the expression of Nrf2, HO-1, and Nqo1 was determined by real-time RT-PCR. Superoxide dismutase (SOD) and malondialdehyde (MDA) in liver homogenate were determined, and liver index was measured. To assess the effects of blueberry on cellular immune function, male mice received blueberry (0.4, 0.6, or 0.8 g/10 g) for 35 days, and the percentages of CD3+, CD4+, and CD8+ T lymphocyte subgroups in peripheral blood were detected by flow cytometry, the index of the thymus and spleen was measured, and lymphocyte proliferation in the spleen was determined by MTT assay.

RESULTS: Blueberry treatment significantly increased the expression of Nrf2, HO-1, and Nqo1, the important antioxidant components in the liver. Hepatic SOD in the blueberry group was higher and MDA was lower than that in the control group (P<0.05). Blueberry also increased the index of the spleen and enhanced the proliferation of lymphocytes of the spleen (P<0.05). The percentages of the CD3+ and CD4+ T lymphocyte subsets and the CD4+/CD8+ ratio were also increased by blueberry (P<0.05).

CONCLUSIONS: Blueberry induces expression of Nrf2, HO-1, and Nqo1, which can protect hepatocytes from oxidative stress. In addition, blueberry can modulate T-cell function in mice.

 

Anthocyanins: Janus Nutraceuticals Displaying Chemotherapeutic and Neuroprotective Properties

From: http://link.springer.com/chapter/10.1007/978-94-007-4575-9_21

Abstract

Anthocyanins are natural polyphenolic compounds widely distributed as pigments in many fruits and vegetables. In addition to displaying antioxidant properties, these nutraceuticals exhibit anti-inflammatory, anti-proliferative, and pro-apoptotic activities suggesting their potential as novel chemotherapeutic agents. Through cell cycle down-regulation, and context-specific pro-oxidant activity, anthocyanins induce cytotoxicity in cancer cells in vitro and in vivo. Specifically, via regulation of the Bcl-2 protein family and induction of caspase-dependent or caspase-independent apoptotic pathways, anthocyanins inhibit the growth of cancers by inducing cell death. Moreover, by modulating the activities of specific kinases and proteases, including (but not limited to) cyclin-dependent kinases, mitogen-activated protein kinases, matrix metalloproteases, and urokinase-type plasminogen activators, anthocyanins induce apoptosis, inhibit motility, and suppress invasion of cancer cells. In marked contrast to their effects in cancer cells, we have found that anthocyanins display significant anti-apoptotic activity in neurons. Antioxidant properties of these nutraceuticals, particularly at the level of the mitochondria, appear to underlie their neuroprotective effects. The opposing effects of anthocyanins on cancer cells and neurons suggest that these nutraceuticals are promising candidates for development as either chemotherapeutic agents or novel neuroprotective compounds for the treatment of cancers or neurodegenerative diseases, respectively.

Recent Research on Polyphenolics in Vision and Eye Health

From: http://pubs.acs.org/doi/abs/10.1021/jf903038r#end-1

Abstract

A long-standing yet controversial bioactivity attributed to polyphenols is their beneficial effects in vision. Although anecdotal case reports and in vitro research studies provide evidence for the visual benefits of anthocyanin-rich berries, rigorous clinical evidence of their benefits is still lacking. Recent in vitro studies demonstrate that anthocyanins and other flavonoids interact directly with rhodopsin and modulate visual pigment function. Additional in vitro studies show flavonoids protect a variety of retinal cell types from oxidative stress-induced cell death, a neuroprotective property of significance because the retina has the highest metabolic rate of any tissue and is particularly vulnerable to oxidative injury. However, more information is needed on the bioactivity of in vivo conjugates and the accumulation of flavonoids in ocular tissues. The direct and indirect costs of age-related vision impairment provide a powerful incentive to explore the potential for improved vision health through the intake of dietary polyphenolics.

 

Bilberry Extracts Induce Gene Expression Through the Electrophile Response Element

From: http://www.tandfonline.com/doi/abs/10.1207/s15327914nc5401_11#.VLK6LVqBO24

Abstract

A number of genes important for detoxification and antioxidant defense induced by mild stress generated by, for example, physical activity/exercise, caloric restriction, or alcohol may provide health benefits by causing the organism to mount such a defense response. More recently, induction of these defenses has also been attributed to phytochemicals or secondary metabolites from dietary plants. Many polyphenols, which constitute a large fraction of these phytochemicals, increase cellular levels of antioxidants, such as glutathione and other components of the detoxification systems, via the transactivation of genes containing electrophile response elements (EpREs) within their promoters. One such gene, γ-glutamylcysteine synthetase, has previously been shown to be positively regulated by quercetin, a flavonoid found in high concentrations in onions, apples, and bilberries through EpRE transactivation. As a further step, we have investigated whether bilberries and quercetin have the ability to induce transcription of Fos-related antigen 1 (Fra-1), which contains two EpREs in its promoter. Fra-1 is a member of the activator protein 1 (AP-1) family of transcription factors and, due to the lack of transactivation domain Fra-1, can suppress activation of AP-1. We present results demonstrating that extracts from bilberries, and the flavonoid quercetin, abundant in bilberries, induce the fra-1 promoter and the cellular content of Fra-1 mRNA. We further provide evidence that this induction is mediated through EpREs.

 

Bilberry (Vaccinium myrtillus)

From: http://www.sigmaaldrich.com/life-science/nutrition-research/learning-center/plant-profiler/vaccinium-myrtillus.html

Synonyms / Common Names / Related Terms
Airelle, anthocyanins, Bickbeere (German), bilberry leaf, black whortle, Blaubeere (Dutch), blaubessen, bleaberry, blueberry, blueberry leaf, bogberry, bog bilberry, burren myrtle, cranberry, dwarf bilberry, dyeberry, Ericaceae (family), European blueberry, Heidelbeere (Dutch), Heidelbeereblatter, heidelberry, huckleberry, hurtleberry, lingonberry, lowbush blueberry, Mirtillo nero (Italian), Myrtilli folium, Myrtilli fructus, Myrtilus niger Gilib., Optiberry, resveratrol, sambubiosides, trackleberry, Vaccinium angulosum Dulac, Vaccinium montanum Salibs., Vaccinium myrtillus anthocyanoside extract, VMA extract, VME, whortleberry, wineberry
Mechanism of Action

Pharmacology:

  • Constituents: Bilberry contains several compounds that have demonstrated biological activity. The main chemicals contained in bilberry extract have been shown to be: anthocyanins30,31, flavonoids, hydroquinone, oleanolic acid, neomyrtillin, sodium, tannins, and ursolic acid17,20,32,33,34. Bilberry also contains resveratrol.28,29 The anthocyanosides, tannins, and flavonoids have been of particular scientific interest. Flavonoids have been shown in vitro to possess a number of biological properties, including inhibition of prostacyclin synthesis, reduction of capillary permeability and fragility, free radical scavenging, inhibition of a wide range of enzymes, impairment of coagulation and platelet aggregation, and anticarcinogenicity.33,5
  • Mechanism of action: Anthocyanins and other phenolics from bilberry upregulate the oxidative stress defense enzymes heme-oxygenase-1 and glutathione S-transferase-pin cultured human retinal pigment epithelial cells, suggesting that they stimulate signal transduction pathways, influencing genes controlled by the antioxidant response element.30
  • Antibacterial effects: In an in vitro study using Staphylococcus aureus, Staphylococcus aureus Oxford, Enterococcus faecalisBacillus subtilis, and Escherichia coli, an aqueous extract of bilberry leaves had a MIC of 12.7-17.8mg/mL and an aqueous extract of bilberry fruit had a MIC of 15.4-30.7mg/mL.24
  • Anticarcinogenic effects: In an in vitro study, anthocyanin-rich extracts from bilberry (Vaccinium myrtillus L.) inhibited the growth of a colon cancer cell line.6
  • Bomser et al. screened fruit extracts of bilberry for potential anticarcinogenic compounds by a combination of fractionation and in vitro testing of their ability to induce the Phase 2 xenobiotic detoxification enzyme quinone reductase (QR) and to inhibit the induction of ornithine decarboxylase (ODC), the rate-limiting enzyme in polyamine synthesis, by the tumor promoter phorbol 12-myristate 13-acetate (TPA).5 The crude extracts, anthocyanin, and proanthocyanidin fractions were not found to be highly active in Phase 2 xenobiotic detoxification enzyme quinone reductase (QR) induction, whereas the ethyl acetate extracts were active QR inducers. The concentrations required to double QR activity (designated CDqr) for the ethyl acetate extracts of bilberry were 1.0mcg tannic acid equivalents (TAE). Further fractionation of the bilberry ethyl acetate extract revealed that the majority of inducer potency was contained in a hexane/chloroform subfraction (CDqr = 0.07mcg TAE). The anthocyanidin and ethyl acetate extracts of bilberry were either inactive or relatively weak inhibitors of ornithine decarboxylase (ODC) activity. The authors concluded that components of the hexane/chloroform fraction of bilberry exhibit potential anticarcinogenic activity, as evaluated by in vitro screening tests.
  • Antihyperglycemic effects: In normal and depancreatized dogs, oral administration of bilberry leaves reduced hyperglycemia, even when the glucose was injected intravenously concurrently.15,16
  • Antioxidant effects: Bilberry contains anthocyanosides that are flavonoid derivatives of anthocyanins (the blue, red, or violet pigments found in many berry varieties), which are closely related in structure and activity to flavonoids17 and possess free radical scavenging/antioxidant properties. Antioxidant properties have been attributed to bilberry based on in vitro studies.1,2,34
  • Antiplatelet activity: In a clinical study of 30 subjects with normal platelet aggregation, 480mg of Myrtocyan® (Vaccinium myrtillus anthocyanins) daily, 3g of ascorbic acid daily, or both treatments all reduced platelet aggregation after 30 and 60 days.11 Bilberry anthocyanins reduced platelet aggregation more than ascorbic acid alone, but bilberry anthocyanins and ascorbic acid together were the most effective. Also, in in vitro studies, anthocyanins extracted from bilberry have inhibited platelet aggregation.13,14,10,12
  • Flavonoids have been shown in vitro to inhibit prostacyclin synthesis. In one animal model, Vaccinium myrtillus anthocyanosides were studied for their effects on prostacyclin-like activity in rat arterial issue.7
  • Antiproliferative effects: According to one laboratory study, anthocyanins were the predominant phenolic compounds in bilberry extracts.31 Compared to other plants with anthocyanins, such as black currant or lingonberry, cell growth inhibition was greater for bilberry than other plants studied. The pro-apoptosis marker, Bax, was increased 1.3-fold in bilberry-treated cells, whereas the pro-survival marker, Bcl-2, was detected only in control cells. The results demonstrated that bilberry and other berry extracts containing anthocyanins inhibited cancer cell proliferation, mainly via the p21WAF1 pathway.
  • Antiulcer effects: In an animal study, large doses of cyanidin chloride from bilberry significantly increased gastric mucosal release of prostaglandin E2.19 In animal models of gastric ulcers, cyanidin chloride showed antiulcer activity.26,8
  • Astringent effects: Bilberry contains tannins that have been used medicinally as astringents and to treat diarrhea.
  • Connective tissue stabilizing effects: An in vitro study has suggested that anthocyanosides appear to stabilize connective tissue by enhancing collagen synthesis, inhibiting collagen degradation, and enhancing collagen cross linking.35 In contrast, Boniface et al. found a significant decrease in connective tissue synthesis (collagen and glycoproteins) in gingival tissue samples of 12 adult diabetics treated with 600mg of anthocyanosides daily for two months.36
  • Hepatoprotective activity: In an animal study, anthocyans exerted a protective effect on liver cells.27
  • Hyperglycemic effects: In an oral glucose tolerance test in healthy rats, an alcoholic extract of Vaccinium myrtillus leaves increased serum glucose levels compared to controls.25
  • Hypotensive effects: Bilberry has been theorized to potentially drop blood pressure, based on pre-clinical evidence of vascular smooth muscle-relaxing properties.21,22,23
  • Anthocyanoside extracts have been shown to have smooth muscle-relaxing activity, which may account for their purported effects in one series of women with dysmenorrhea.18 Bioflavonoids and extracts of anthocyanosides (such as those present in bilberry) have been shown to relax vascular smooth muscles in experimental models, possibly via stimulation of prostaglandins.21,22,23
  • Intracellular signaling effects: Anthocyanosides have been shown to inhibit cAMP phosphodiesterase, which is involved in intracellular signal transduction pathways.8
  • Ocular effects: Anthocyanosides have been shown to exert direct effects on the retina, including the alteration of local enzymatic reactions and enhancement of the recovery of rhodopsin.9 The multi-ingredient product Mirtogenol (Pycnogenol® – French maritime pine bark extract and Mirtoselect® – standardized bilberry extract) has been reported to lower intraocular pressure and improve ocular blood flow.37
  • Smooth muscle relaxant effects: Anthocyanoside extracts have been shown to have smooth muscle-relaxing activity, which may account for their purported effects in one series of women with dysmenorrhea.18 Bioflavonoids and extracts of anthocyanosides (such as those present in bilberry) have been shown to relax vascular smooth muscles in experimental models, possibly via stimulation of prostaglandins.21,22,23
  • Vasoprotective effects: Flavonoids have been shown in vitro to reduce capillary permeability and fragility. Anthocyanosides have been studied for their potential protective effect in disorders due to abnormal capillary fragility.33

Pharmacodynamics/Kinetics:

  • There are limited data regarding the pharmacodynamics and kinetics of Vaccinium myrtillus (bilberry) anthocyanosides (VMA). In one animal study, bilberry anthocyanosides were rapidly distributed after intra-peritoneal injection and intravenous administration.38 In another animal study, bilberry anthocyanosides were found to be eliminated via the bile and urine with a modest level of liver extraction.32
  • Bioavailability in animals is low. Following oral doses in rats, plasma levels of VMA reached a peak at 15 minutes and declined rapidly within two hours, and the absolute bioavailability was 1.2% of the administered dose.38 The gastrointestinal absorption of VMA was 5% of the administered dose. Another study found a differential affinity of VMA for certain tissues (especially skin and kidney).20 This suggests that different tissues may have more persistent local concentrations.
References:

  1. Martin-Aragon S, Basabe B, Benedi JM, and et all. In vitro and in vivo antioxidant properties of Vaccinium myrtillus. Pharmaceutical Biology 1999;37(2):109-113.
  2. Prior R, Cao G, Martin A, and et all. Antioxidant capacity as influence by total phenolic and anthocyanin content, maturity, and variety of Vaccinium species. J Agricult Food Chem 1998;46:2686-2693.
  3. Martin-Aragon S, Basabe B, Benedi J, and et all. Antioxidant action of Vaccinium myrtillus L. Phytotherapy 1998;46:S104-S106.
  4. Laplaud, P. M., Lelubre, A., and Chapman, M. J. Antioxidant action of Vaccinium myrtillus extract on human low density lipoproteins in vitro: initial observations. Fundam Clin Pharmacol 1997;11(1):35-40. 9182074
  5. Bomser, J., Madhavi, D. L., Singletary, K., and Smith, M. A. In vitro anticancer activity of fruit extracts from Vaccinium species. Planta Med 1996;62(3):212-216.
  6. Zhao, C., Giusti, M. M., Malik, M., Moyer, M. P., and Magnuson, B. A. Effects of commercial anthocyanin-rich extracts on colonic cancer and nontumorigenic colonic cell growth. J Agric Food Chem  10-6-2004;52(20):6122-6128. 15453676
  7. Morazzoni P and Magistretti MJ. Effects of Vaccinium myrtillus anthocyanosides on prostacyclin-like activity in rat arterial issue. Fitoterapia 1986;57:11-14.
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SUMMARY

Wild bilberries and wild blueberries are important fruits full of polyphenols, anthocyanins, antioxidants, and Nrf2 activators that help to make Ultimate Protector such an outstanding nutritional supplement.

 

up-4 elderberry wild bilberry and wild blueberry

Ultimate Protector provides wild bilberry and wild blueberry, and 27 other Nrf2 activator-containing plant-based ingredients.

ADDITIONAL RESOURCES