Antioxidant Activity and its Role in Disease Prevention

Antioxidant Activity and its Role in Disease Prevention

Anthocyanins have often been studied for their antioxidant capabilities and resulting health benefits. Artemis International’s products have been standardized to high anthocyanin levels with significant antioxidant capacity, as indicated by the ORAC (Oxygen Radical Absorbance Capacity) test conducted through Brunswick Laboratories. The ORAC test measures the antioxidant activity of a substance by assessing its ability to retain fluorescence as compared to Trolox. The following section outlines some significant findings with regard to Artemis’ berry extracts and their effects on various health aspects.

Abuja and collaborators in Graz, Austria investigated the impact of the antioxidant and prooxidant properties of Artemis’ standardized elderberry extract and their mechanism of action in lipid peroxidation. Testing was done with both copper- and peroxyl-radicals. A steady-state concentration of the anthocyanins from elderberry (Sambucus nigra) was found to give antioxidant protection, both from copper-induced LDL oxidation and from the attaché of peroxyl radicals. They found that the action of the antioxidant substances from elderberry juice was similar to that of vitamin C.

Abuja, P.M., Murkovic, M., and Pfannhauser, W. 1998. Antioxidant and prooxidant activities of elderberry (Sambucus nigra) extract in low-density lipoprotein oxidation . J. Agric. Food Chem. 46: 4091-4096.

Another group of researchers from Austria and Romania collaborated to conduct a human study on the influence of Artemis’ elderberry extract (standardized to anthocyanins) upon blood parameters related to oxidative stress. The subjects ingested 1500mg of elderberry extract for 10 days and various blood parameters were measured before and after the treatment period. The results showed significant increases in erythrocyte superoxide dismutase (SOD) and catalase—two endogenous antioxidant enzymes. Since highly reactive oxygen radicals can inactivate these enzymes, it is proposed that the anthocyanins indirectly stimulate these enzymes by scavenging the free radicals. In other words, the anthocyanins indirectly act as molecular stimulators of the body’s own antioxidant self-defense mechanisms.

Bratu, M.M., Porta, S., Balaban, D.P., Roncea, F., Negreanu-Pirjol, T., Belc, M.C., Petcu, L.C.2008. Influence of an anthocyanin-rich extract upon blood parameters related to oxidative stress . Archives of the Balkan Medical Union. 43(4): 256-259.

Cardiovascular Support

A human clinical study on vascular reactivity was performed by researchers at Saint Mary’s College in Indiana. The study showed that short-term supplementation with Artemis’ BerryDefense™ increased the flow-mediated dilation of the brachial artery in normal subjects. These findings support the ability of BerryDefense™ to aid in the prevention of atherosclerosis disease development.

Gerlib, K.E., Kelley, B.D., and Mirro, M.J. 2002. Effect of anthocyanins on vascular reactivity in normal subjects. Pilot Study. St. Mary’s College, Notre Dame, IN, Indiana University School of Medicine, Fort Wayne, IN.

Researchers at the Military Medical Academy in Poland conducted a cardiology clinical trial where patients with myocardial infarction (MI) were treated with Artemis’ Standardized Chokeberry extract. This study suggested that the chokeberry extract intake reduced systolic and diastolic blood pressure and reduced levels of plasma angiotensin converting enzyme (ACE) activity in these patients. Additionally, it was illustrated that chokeberry reduced LDL oxidation and inhibited factors that mediated inflammation. Patients also had significant decreases in C-reactive protein (CRP) levels. This protein is presently regarded as one of the most important indicators for a high risk of ischemic heart disease.

Naruszewicz, M., Dluzinewski, M., Laniewska, I., Millo, B., and Bukowska, H. 2003. Effect of chokeberry anthocyanins on the activity of the angiotensin converting enzyme and on the adiponectin level in patients with coronary heart disease (CHD). Merkuriusz Lekarski.

In 2012, 25 patients with hypercholesterolemia (high blood cholesterol) with no pharmacological treatment took 100 mg of the same Artemis’ Standardized Chokeberry extract two times/day for two months. Blood samples were collected from the test group and a control group of 20 healthy individuals at the beginning of the study and at one and two months. Cholesterol decreased in the chokeberry group by 22% and lipid peroxidation decreased by 40%. No significant changes in other measured blood parameters occurred (thiol groups levels, total ATPase activity, or Na+K+ ATPase activity).

Duchnowicz P, Nowicka A, Koter-Michalak M, Broncel M. In vivo influence of extract from Aronia melanocarpon the erythrocyte membranes in patients with hypercholesterolemia. Med Sci Monit. 2012;18(9):CR569-574.

Dr. David Bell, Indiana University School of Medicine – Fort Wayne, IN, conducted in vitro tests with Artemis’ standardized extracts – Bilberry, Chokeberry, Elderberry, and Mixed Berry Blend to determine their effects on porcine coronary arterial function. He found that the Chokeberry, Bilberry and Mixed Berry Blend had direct vasorelaxation effects. These extracts produced a specific type of vasodilation (endothelium dependent- NO-mediated) rather than acting as general non-specific smooth muscle relaxants. He also found that this relaxation was not related to total anthocyanin or total phenolic content, which indicates that a specific component or components of the extracts are vasoactive. Further testing at the same anthocyanin concentration showed that the extracts did not impair the arteries in regards to important vascular physiological functions (e.g. NO- mediated vasorelaxation).

In another set of experiments, Dr. Bell induced superoxide injury in the porcine coronary arteries. He found that a physiological concentration of Artemis’ standardized chokeberry extract (which was too low to cause direct vasodilation of the arteries and too low to cause modification of normal responses to endothelium dependent and independent NO-mediated vasodilation) completely protected the coronary arteries from oxidant injury. The bilberry and elderberry extracts provided partial, but not complete, protection against oxidant injury.

Bell, D.R. and Gochenaur, K. 2002. Characterization of coronary arterial reactivity of berry anthocyanins. Presented at Experimental Biology 2002, April 20-24, New Orleans, LA.

Bell, D.R. and Gochenaur, K. 2005. Direct vasoactive and vasoprotective properties of anthocyanin-rich extracts. J Appl Physiol. 100: 1164-1170.

Researchers at the Jean Mayer Human Nutrition Research Center on Aging at Tufts University investigated the ability of endothelial cells to incorporate anthocyanins and examined the potential benefits against various oxidative stressors, using Artemis’ standardized elderberry extract. They found that incorporation of elderberry anthocyanins by the endothelial cells significantly enhanced their resistance to the damaging effects of oxidative insult. Untreated, the damaging effects may lead to endothelial dysfunction, which may be involved in the initiation of vascular disease.

Youdim, K.A., Martin, A., and Joseph, J.A. 2000. Incorporation of the elderberry anthocyanins by endothelial cells increases protection against oxidative stress. Free Radical Biology & Medicine. 29(1): 51-60.

Another study in 2012 investigated the effect of short-term supplementation with black chokeberry extract on blood clot formation, platelet aggregation (which leads to clot formation), and fibrinolysis (a process preventing the growth of blood clots) in patients with metabolic syndrome. Patients with metabolic syndrome and healthy volunteers were enlisted and patients were given 100 mg chokeberry extract (60 mg total polyphenols, including a minimum of 20 mg anthocyanins) three times/day for two months while the control group received nothing. All participants started a low-fat diet three month prior to taking the chokeberry extract, were instructed not to modify their usual food intake or exercise, and were prohibited from ingesting black chokeberry products. Body mass index (BMI) and waist circumference were measured, urine analysis was performed, and blood was drawn prior to supplementation, at one month and at two months. Blood was analyzed for total and differential blood cell count, blood sedimentation rate, alanine and aspartate aminotransferases, electrolytes, bilirubin, creatinine, and total proteins. Additional blood assays were done for total serum cholesterol (TC), triglycerides (TG), HDL and LDL cholesterol (HDLc and LDLc), and fibrinogen levels. After one and two months of chokeberry supplementation, the treatment group showed significant decreases in TC, LDLc, and TG; and no changes in HDLc, BMI, or waist circumference occurred. After one month of supplementation the treatment group experienced a statistically significant change in inhibition of platelet aggregation. However, these values returned to the pre-study levels after two months of supplementation. Potential for clot formation and fibrinolysis decreased significantly in the treatment group after one month of supplementation, and the maximum of coagulation and fibrinolysis and times of these processes were also reduced.

Sikora J, Broncel M, Markowicz M, Chalubinski M, Wojdan K, Mikiciuk-Olasik E. 2012. Short-term supplementation with Aronia melanocarpa extract improves platelet aggregation, clotting, and fibrinolysis in patients with metabolic syndrome. Eur J Nutr. 51:549-556.

A 2010 study examined the effect of black chokeberries on blood pressure (BP), serum concentrations of lipids (TC, LDLc, HDLc, TG), endothelin-1 (ET-1), inflammatory mediators (C-reactive protein and fibrinogen), fasting glucose, and uric acid in patients with MetS.23 One group of participants included 25 MetS patients who had not responded to a three-month lifestyle modification. The second group included 22 healthy volunteers matched for age and gender. The treatment group was given 100 mg aronia extract (Aronox [64.5% 3-O-cyanidin-galactoside, 28.9% 3-O-cyanidin-arabinoside, 4.2% 3-O-cyanidin-xyloside, and 2.4% 3-O-cyanidin-glucoside], Agropharm SA, Tuszyn, Poland) three times daily over a two-month period. Clinical examinations, measurements of weight, waist circumference, BP, urine examinations, 12-ECG, and blood sampling were done before treatment initiated and after one and two months. Two months of aronia extract supplementation resulted in significant decreases in systolic and diastolic BP as well as in concentrations of TC, LDLc, TG, and ET-1, suggesting that aronia supplementation may benefit MetS patients with regard to atherosclerosis prevention.

Broncel M, Koziróg M, Duchnowicz P, Koter-Michalak M, Sikora J, Chojnowska-Jezierska J. Aronia melanocarpa extract reduces blood pressure, serum endothelin, lipid, and oxidative stress marker levels in patients with metabolic syndrome. Med Sci Monit. 2010;16(1);CR28-34.

See Appendix I for additional research supporting the protective effects of high anthocyanin berry extracts against vascular disease.

Protection Against Diabetes and Gastric Diseases

Researchers at the Military Medical Academy in Poland conducted studies to assess the effects of Artemis’ Standardized Chokeberry extract on induced diabetes in laboratory rats. They found that after ingestion of the Chokeberry extract, glucose levels in the urine and in various organs decreased and the amount of lipid peroxidation (measured in TBARS) also decreased. They also found that rats ill with diabetes lost significant amounts of body weight, whereas treatment with the chokeberry extract resulted in maintenance of their normal body weight. An additional human study conducted on pregnant women with insulin-dependent diabetes revealed a statistically significant decrease in HbA1c-glycosylated hemoglobin levels when the chokeberry extract was consumed, as compared to controls. This suggests that Artemis’ Standardized Chokeberry extract helps to normalize carbohydrate metabolism in pregnant women with uncontrolled insulin-dependent diabetes.

Jankowski, A., Jankowska, B.,and Niedworok, J. 1999. Influence of anthocyanins from aronia melanocarpa Elliot on the course of experimental diabetes. Diabetologia Polska. 6: 67-95.

Pawlowicz, P. 2000. Influence of natural anthocyanins derived from chokeberry (Aronia melanocarpa) extract on glycosylated hemoglobin level in pregnant women with insulin-dependent diabetes mellitus. Poland.

The most probable cause of acute pancreatitis is the depletion of the body’s natural ability to neutralize free radicals. Therefore, it may be expected that application of antioxidants should have a beneficial influence on the course of the disease, due to the direct inhibition of reactive oxygen species or due to the stimulation of natural enzymatic antioxidant systems. Researchers at the Military Medical Academy in Poland tested the effects of Artemis’ Standardized Chokeberry extract on the course of induced acute pancreatitis in vivo in rats. With incorporation of the chokeberry extract, they reported a significant reduction of edema, a decrease in the concentration of α-amylase in the urine, and inhibition of an increase in lipid peroxidation by free radicals. Therefore, the researchers indicated that the Artemis’ Standardized Chokeberry extract prevented the development of pancreatitis.

Jankowska, B., Jankowski, A., and Niedworok, J. 1999. Influence of natural anthocyanins from Aronia melanocarpa on course of acute experimental pancreatitis in rats. Military Medical Academy, Poland.

In recent years researchers have been investigating the role of oxygen free radicals and lipid peroxidation in the development of gastric mucosal damage. In a study conducted by researchers at the Military Medical Academy in Poland, Artemis’ Standardized Chokeberry extract was orally administered to mice with ethanol-induced extensive hemorrhage necrosis in the gastric mucosa. They observed a potent, dose-dependent protective effect against acute gastric lesions, compared to controls.

Niedworok, J., Jankowska, B., Kowalczyk, D., Charyk, K., and Kubat, Z. 1997. Antiulcer activity of anthocyanin from aronia melanocarpa elliott. Herba Polonica.

See Appendix I for additional research supporting the protective effects of high anthocyanin berry extracts against gastric mucosal damage.

Protection Against Radiation Damage

Researchers at the Military Medical Academy in Poland researched the effect of a gel made from Artemis’ Standardized Chokeberry extract against ultraviolet (UV) radiation damage. It has been well established that UV radiation can be harmful due to direct DNA damage and the generation of free radicals. It is also known that in photosynthetic tissues (such as leaves), anthocyanins have been shown to act as a “sunscreen,” protecting cells from photo-damage by absorbing UV and blue-green light, thereby protecting the tissues from photoinhibition (high light stress). The researchers found that application of the anthocyanin-rich chokeberry gel does decrease UV damage in rat models and therefore, could possibly be used for UV protection.

Niedworok, J., Gwardys, A., Jankowski, A., Kowalczyk, E., Oszmiański, J., and Skośkiewicz, J. 1999. The investigation of the protective effect of anthocyanin gel against phototoxic UV radiation. Ochrona Środowiska i Zasobów Naturalnych.

The same researchers investigated the antioxidant effects of Artemis’ Standardized Chokeberry extract in rabbits that had been treated with gamma radiation and cadmium chloride in an effort to reverse the destructive effects of radiation exposure. Generation of free radicals results from radiation exposure and plays an essential role in radiation sickness pathogenesis. Treatment with Artemis’ Standardized Chokeberry extract resulted in decreased amounts of superoxide ion generation after radiation exposure.

Andryskowski, G., Niedworok, J., Maziarz, Z., and Małkowski, B. 1998. The effect of natural anthocyanin dye on superoxide radical generation and chemiluminescence in animals after absorbed 4 Gy dose of gamma radiation. Polish Journal of Environmental Studies. 7(6).

See Appendix I for additional research supporting the protective effects of high anthocyanin berry extracts against UV radiation damage.

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