Life Extension Magazine September 2008
Increases in human plasma antioxidant capacity after consumption of controlled diets high in fruit and vegetables.
BACKGROUND: The putative beneficial effects of an increased consumption of fruit and vegetables have been associated with antioxidant nutrients. However, the effect of fruit and vegetable consumption on the overall antioxidant status in humans is unclear. OBJECTIVE: The objective of this study was to investigate whether a diet rich in fruit and vegetables would affect the antioxidant capacity of human plasma. DESIGN: Thirty-six healthy nonsmokers resided in a metabolic research unit and consumed 2 sets of controlled diets. Diet A contained 10 servings of fruit and vegetables each day for 15 d. Diet B was the same as diet A, except diet B also provided 2 servings of broccoli each day on days 6-10. There was a free-living period of a minimum of 6 wk between the 2 experiments using either diet A or diet B. Fasting plasma antioxidant capacity, measured as oxygen radical absorbance capacity (ORAC), and alpha-tocopherol concentrations were determined on days 1, 6, 11, and 16. RESULTS: The fasting baseline plasma ORAC of these subjects was significantly correlated with their estimated daily intake of total antioxidants from fruit and vegetables during the previous year. Plasma ORAC of these subjects was significantly increased by both diets A and B. This increase in ORAC could not be explained by the increase in the plasma alpha-tocopherol concentration. CONCLUSION: Increased consumption of fruit and vegetables can increase the plasma antioxidant capacity in humans.
Am J Clin Nutr. 1998 Nov;68(5):1081-7
Berry fruits for cancer prevention: current status and future prospects.
Overwhelming evidence suggests that edible small and soft-fleshed berry fruits may have beneficial effects against several types of human cancers. The anticancer potential of berries has been related, at least in part, to a multitude of bioactive phytochemicals that these colorful fruits contain, including polyphenols (flavonoids, proanthocyanidins, ellagitannins, gallotannins, phenolic acids), stilbenoids, lignans, and triterpenoids. Studies show that the anticancer effects of berry bioactives are partially mediated through their abilities to counteract, reduce, and also repair damage resulting from oxidative stress and inflammation. In addition, berry bioactives also regulate carcinogen and xenobiotic metabolizing enzymes, various transcription and growth factors, inflammatory cytokines, and subcellular signaling pathways of cancer cell proliferation, apoptosis, and tumor angiogenesis. Berry phytochemicals may also potentially sensitize tumor cells to chemotherapeutic agents by inhibiting pathways that lead to treatment resistance, and berry fruit consumption may provide protection from therapy-associated toxicities. Although a wide variety of berry fruits are consumed worldwide, this paper focuses on those commonly consumed in North America, namely, blackberries, black raspberries, blueberries, cranberries, red raspberries, and strawberries. In addition, a large body of studies on singly purified berry bioactives is available, but this paper focuses on studies of “whole berries” per se, that is, as berry extracts and purified fractions, juices, and freeze-dried powders. Potential mechanisms of anticancer action and bioavailability of berry phenolics, as well as gaps in knowledge and recommendations for future berry research, are also briefly discussed.
J Agric Food Chem. 2008 Feb 13;56(3):630-5
Hypoglycemic and hypolipidemic effects of Aronia melanocarpa fruit juice in streptozotocin-induced diabetic rats.
Aronia melanocarpa fruit juice (AMFJ) is rich in phenolic antioxidants, especially flavonoids from the anthocyanin subclass. The aim of the present study was to investigate the influence of AMFJ on plasma glucose and lipids in diabetic rats. Diabetes was induced by an intraperitoneal injection of streptozotocin (50 mg/kg). AMFJ was applied by gavage at doses of 10 and 20 ml/kg for 6 weeks to normal and diabetic rats. Streptozotocin caused a significant elevation of plasma glucose by 141% and of plasma triglycerides (TG) by 64% in comparison with normal control rats and induced statistically insignificant elevations of total cholesterol and LDL-cholesterol and a reduction of HDL-cholesterol. Applied to normal rats, AMFJ did not influence plasma glucose and lipid levels. Applied to diabetic rats, AMFJ (10 and 20 ml/kg) significantly reduced plasma glucose by 44% and 42% and TG by 35% and 39%, respectively, to levels that did not significantly differ from those of the normal control rats and counteracted the influence of streptozotocin on total cholesterol, LDL-cholesterol and HDL-cholesterol. In conclusion, AMFJ significantly decreased the streptozotocin-induced abnormalities in blood glucose and TG in diabetic rats and might be useful in prevention and control of diabetes mellitus and diabetes-associated complications.
Methods Find Exp Clin Pharmacol. 2007 Mar;29(2):101-5
Fruit polyphenolics and brain aging: nutritional interventions targeting age-related neuronal and behavioral deficits.
Nutritional interventions, in this case, increasing dietary intake of fruits and vegetables, can retard and even reverse age-related declines in brain function and in cognitive and motor performance in rats. Our lab has shown that as Fischer 344 rats age their brains are increasingly vulnerable to oxidative stress. Dietary supplementation with fruit or vegetable extracts high in antioxidants (e.g., blueberry, BB, spinach, respectively) can decrease this vulnerability to oxidative stress as assessed in vivo by examining reductions in neuronal signaling and behavioral deficits and in vitro via H2O2-induced decrements in striatal synaptosomal calcium buffering. Examinations have also revealed that BB supplementations are effective in antagonizing other age-related changes in brain and behavior, as well as decreasing indices of inflammation and oxidative stress in gastrocnemius and quadriceps muscles. In ongoing studies we are attempting to determine the most effective BB polyphenolic components. To date, the anthocyanins show the most efficacy in penetrating the cell membrane and in providing antioxidant protection. In sum, our results indicate that increasing dietary intake of fruits and vegetables high in antioxidant activity may be an important component of a healthy living strategy designed to maximize neuronal and cognitive functioning into old age.
Ann N Y Acad Sci. 2002 Apr;959:128-32
Blueberry supplementation enhances signaling and prevents behavioral deficits in an Alzheimer disease model.
Previously, we showed that blueberry (BB) supplementation reversed the deleterious effects of aging on motor behavior and neuronal signaling in senescent rodents. We now report that BB-fed (from 4 months of age) APP + PS1 transgenic mice showed no deficits in Y-maze performance (at 12 months of age) with no alterations in amyloid beta burden. It appeared that the protective mechanisms are derived from BB-induced enhancement of memory-associated neuronal signaling (e.g. extracellular signal-regulated kinase) and alterations in neutral sphingomyelin-specific phospholipase C activity. Thus, our data indicate for the first time that it may be possible to overcome genetic predispositions to Alzheimer disease through diet.
Nutr Neurosci. 2003 Jun;6(3):153-62
Direct vasoactive and vasoprotective properties of anthocyanin-rich extracts.
Reactive oxygen species (ROS) play a critical role in the impairment of nitric oxide-mediated vascular functions and overall pathogenesis associated with cardiovascular disease. Plant pigment anthocyanins are exceptionally potent oxygen radical scavengers that produce beneficial effects in diseases outside the cardiovascular system. We examined for the first time the potential coronary vasoactive and vasoprotective properties of three anthocyanin enhanced extracts prepared from chokeberry (Ck), bilberry (B), or elderberry (E). Coronary arterial rings were isolated from 64 pigs and incubated in sterile tissue culture media overnight for use in one of four separate in vitro isometric force recording studies. Ck and B, but not E, produced dose- and endothelium-dependent vasorelaxation. (%maximal relaxation at 5 mg total anthocyanins per liter: Ck = 68 +/- 11, B = 59 +/- 10). Coronary vascular tone, endothelium-dependent vasorelaxation to A23187, and vasorelaxation to DEA NONOate were not affected by exposure of rings to any extract at 0.05 mg total anthocyanins per liter for 5 or 30 min. Ck extract at 0.05 mg total anthocyanins per liter showed the greatest protection against loss of A23187 relaxation following exposure to ROS from pyrogallol (Ck, % maximal relaxation and -logED50 to A23187, respectively, means +/- SE: Ck alone, 93 +/- 5%, 7.91 +/- 0.1; pyrogallol alone, 76 +/- 7%, 7.46 +/- 0.06; pyrogallol + Ck, 98 +/- 1%, 7.82 +/- 0.06; control: 99 +/- 1%, 7.86 +/- 0.07; P < 0.05 control vs. pyrogallol alone). Neither the extracts nor pyrogallol affected responses to DEA NONOate. Thus anthocyanin-enhanced extracts produce endothelium-dependent relaxation in porcine coronary arteries. Extract concentrations too low to directly alter coronary vascular tone protect coronary arteries from ROS without altering vasorelaxation to endogenous or exogenous NO. These results suggest that such extracts could have significant beneficial effects in vascular disease.
J Appl Physiol. 2006 Apr;100(4):1164-70
Pomegranate juice consumption inhibits serum angiotensin converting enzyme activity and reduces systolic blood pressure.
Consumption of pomegranate juice which is rich in tannins, possess anti-atherosclerotic properties which could be related to its potent anti-oxidative characteristics. As some antioxidants were recently shown to reduce blood pressure, we studied the effect of pomegranate juice consumption (50 ml, 1.5mmol of total polyphenols per day, for 2 weeks) by hypertensive patients on their blood pressure and on serum angiotensin converting enzyme (ACE) activity. A 36% decrement in serum ACE activity and a 5% reduction in systolic blood pressure were noted. Similar dose-dependent inhibitory effect (31%) of pomegranate juice on serum ACE activity was observed also in vitro. As reduction in serum ACE activity, even with no decrement in blood pressure, was previously shown to attenuate atherosclerosis, pomegranate juice can offer a wide protection against cardiovascular diseases which could be related to its inhibitory effect on oxidative stress and on serum ACE activity.
Atherosclerosis. 2001 Sep;158(1):195-8
Antihyperlipidemic effect of Aronia melanocarpa fruit juice in rats fed a high-cholesterol diet.
Aronia melanocrpa fruit juice (AMFJ) used in our experiment was very rich in phenolic substances (709.3 mg gallic acid equivalents/100 ml juice). Anthocyanins (106.8 mg cyanidin-3-glucoside equivalents/100 ml juice) were the main flavonoid group. The aim of this study was to assess the influence of AMFJ on plasma lipids and lipoprotein profile, and histopathology of liver and aorta in rats with dietary-induced hyperlipidemia. AMFJ was administered by gavage for 30 days at doses of 5, 10, and 20 ml/kg body weight to rats fed a standard diet (SD) or a 4% cholesterol-containing diet (4% ChD). The 4% ChD caused a significant elevation of plasma total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG). AMFJ did not significantly influence plasma lipids in rats fed the SD and significantly hindered the elevation of plasma TC, LDL-C and TG in rats fed the 4% ChD. High-density lipoprotein cholesterol (HDL-C) levels were not significantly influenced either by the 4% ChD or by AMFJ. Neither the cholesterol feeding, nor AMFJ treatment induced any histopathological changes in rat liver and aorta. In conclusion, AMFJ showed an antihyperlipidemic effect in rats with hyperlipidemia and could be valuable in reducing this factor of cardiovascular risk.
Plant Foods Hum Nutr. 2007 Mar;62(1):19-24
Natural dietary polyphenolic compounds cause endothelium-dependent vasorelaxation in rat thoracic aorta.
This study investigated the possible active principles which support the endothelial nitric oxide-dependent relaxation produced by red wine and other plant polyphenolic compounds in thoracic aorta from male Wistar rats (12-14 wk old). Relaxation experiments were recorded isometrically on vessels precontracted with norepinephrine. Ten different chromatographic fractions (3-18 mg) isolated from red wine polyphenolic compounds (RWPC) and some available defined polyphenols (10-15 mg) were tested. Fractions enriched into either anthocyanins or oligomeric condensed tannins exhibited endothelium-dependent vasorelaxant activity (maximal relaxation in the range of 59-77%) comparable to the original RWPC. However, polymeric condensed tannins elicited a weaker vasorelaxant activity than the original RWPC (maximal relaxation ranged between 20-47%, P < 0.01). Moreover, the representative of either phenolic acid derivatives (benzoic acid, vanillic acid, gallic acid), hydroxycinnamic acid (p-coumaric acid, caffeic acid) or the flavanol [(+)-epicatechin] classes failed to induce this type of response. Among the anthocyanins, delphinidin (maximal relaxation being 89%), but not malvidin or cyanidin, showed endothelium-dependent vasorelaxation. These results show that anthocyanins and oligomeric-condensed tannins exhibited a pharmacological profile comparable to the original RWPC. These compounds may be involved in the reduction of cardiovascular mortality related to the presence of wine, fruits and vegetables in the diet.
J Nutr. 1998 Dec;128(12):2324-33
Blueberry prevents bone loss in ovariectomized rat model of postmenopausal osteoporosis.
The objective of the present study was to explore the bone protective role of blueberry in an ovariectomized rat model. Thirty 6-month-old female Sprague-Dawley rats were either sham-operated (Sham) or ovariectomized (Ovx) and divided into three groups: Sham, Ovx (control), Ovx+blueberry (5% blueberry w/w). After 100 days of treatment, rats were euthanized, and blood and tissues were collected. Bone mineral density (BMD) and content of whole body, right tibia, right femur, and fourth lumbar vertebra were assessed via dual-energy X-ray absorptiometry. As expected, Ovx resulted in loss of whole-body, tibial, femoral, and 4th lumbar BMD by approximately 6%. Blueberry treatment was able to prevent the loss of whole-body BMD and had an intermediary effect on prevention of tibial and femoral BMD when compared to either Sham or Ovx controls. The bone-protective effects of blueberry may be due to suppression of Ovx-induced increase in bone turnover, as evident by lowered femoral mRNA levels of alkaline phosphatase, collagen type I and tartrate-resistant acid phosphatase to the Sham levels. Similarly, serum osteocalcein levels were also lower in the blueberry group when compared to the Ovx control group, albeit not significantly. In summary, our findings indicate that blueberry can prevent bone loss as seen by the increases in BMD and favorable changes in biomarkers of bone metabolism.
J Nutr Biochem. 2008 Mar 5
Antioxidant capacity and other bioactivities of the freeze-dried Amazonian palm berry, Euterpe oleraceae mart. (acai).
The fruit of Euterpe oleraceae, commonly known as acai, has been demonstrated to exhibit significantly high antioxidant capacity in vitro, especially for superoxide and peroxyl scavenging, and, therefore, may have possible health benefits. In this study, the antioxidant capacities of freeze-dried acai fruit pulp/skin powder (OptiAcai) were evaluated by different assays with various free radical sources. It was found to have exceptional activity against superoxide in the superoxide scavenging (SOD) assay, the highest of any food reported to date against the peroxyl radical as measured by the oxygen radical absorbance capacity assay with fluorescein as the fluorescent probe (ORACFL), and mild activity against both the peroxynitrite and hydroxyl radical by the peroxynitrite averting capacity (NORAC) and hydroxyl radical averting capacity (HORAC) assays, respectively. The SOD of acai was 1,614 units/g, an extremely high scavenging capacity for O2*-, by far the highest of any fruit or vegetable tested to date. Total phenolics were also tested as comparison. In the total antioxidant (TAO) assay, antioxidants in acai were differentiated into “slow-acting” and “fast-acting” components. An assay measuring inhibition of reactive oxygen species (ROS) formation in freshly purified human neutrophils showed that antioxidants in acai are able to enter human cells in a fully functional form and to perform an oxygen quenching function at very low doses. Furthermore, other bioactivities related to anti-inflammation and immune functions were also investigated. Acai was found to be a potential cyclooxygenase (COX)-1 and COX-2 inhibitor. It also showed a weak effect on lipopolysaccharide (LPS)-induced nitric oxide but no effect on either lymphocyte proliferation and phagocytic capacity.
J Agric Food Chem. 2006 Nov 1;54(22):8604-10
Açai (Euterpe oleracea Mart.) polyphenolics in their glycoside and aglycone forms induce apoptosis of HL-60 leukemia cells.
The effects of açai polyphenolics on the antiproliferation and induction of apoptosis in HL-60 human leukemia cells were investigated. Interactions between anthocyanins and non-anthocyanin-polyphenolics in both their glycosidic and their aglycone forms were also investigated to determine additive or nonadditive responses. Polyphenolic fractions at 0.17-10.7 microM were found to reduce cell proliferation from 56 to 86% likely due to caspase-3 activation (apoptosis). Anthocyanin and polyphenolic fractions were nonadditive in their contribution to the cell antiproliferation activity. At equimolar concentrations, the glycosidic forms of phenolic acids and flavonoids induced a higher magnitude of change in cell parameters (proliferation and apoptosis) than their respective aglycone forms, while the opposite trend was observed for anthocyanin aglycones. This study demonstrated that açai offers a rich source of bioactive polyphenolics and confirmed the importance of investigating whole food systems when evaluating the potential health benefits of individual phytochemical compounds.
J Agric Food Chem. 2006 Feb 22;54(4):1222-9
Anthocyanin-rich extracts inhibit multiple biomarkers of colon cancer in rats.
The aim of the present study was to investigate the chemoprotective activity of anthocyanin-rich extracts (AREs) from bilberry (Vaccinium myrtillus L.), chokeberry (Aronia meloncarpa E.), and grape (Vitis vinifera) by assessing multiple biomarkers of colon cancer in male rats treated with a colon carcinogen, azoxymethane. Fischer 344 male rats were fed the AIN-93 diet (control) or AIN-93 diet supplemented with AREs for 14 wk. Biomarkers that were evaluated included the number and multiplicity of colonic aberrant crypt foci (ACF), colonic cell proliferation, urinary levels of oxidative DNA damage, and expression of cyclooxygenase (COX) genes. To assess the bioavailability, levels of anthocyanins in serum, urine, and feces were evaluated. Total ACF were reduced (P<0.05) in bilberry, chokeberry, and grape diet groups compared with the control group. The number of large ACF was also reduced (P<0.05) in bilberry and chokeberry ARE-fed rats. Colonic cellular proliferation was decreased in rats fed bilberry ARE and chokeberry ARE diets. Rats fed bilberry and grape ARE diets had lower COX-2 mRNA expression of gene. High levels of fecal anthocyanins and increased fecal mass and fecal moisture occurred in ARE-fed rats. There was also a significant reduction (P<0.05) in fecal bile acids in ARE-fed rats. The levels of urinary 8-hydroxyguanosine were similar among rats fed different diets. These results support our previous in vitro studies suggesting a protective role of AREs in colon carcinogenesis and indicate multiple mechanisms of action.
Nutr Cancer. 2006;54(1):84-93
Anti-inflammatory effects of aronia extract on rat endotoxin-induced uveitis.
PURPOSE: Aronia crude extract (ACE) with high levels of polyphenol compounds has been reported to have antioxidative effects in vitro and in vivo. In this study, attention was focused on the antioxidant effect of ACE. The purpose of the present study was to investigate the effect of ACE on endotoxin-induced uveitis (EIU) in rats. In addition, the endotoxin-induced expression of the inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 proteins was investigated in a mouse macrophage cell line (RAW 264.7) treated with ACE in vitro, to clarify the anti-inflammatory effect. METHODS: EIU was induced in male Lewis rats by a footpad injection of lipopolysaccharide (LPS). Immediately after the LPS inoculation, 1, 10, or 100 mg ACE or 10 mg prednisolone was injected intravenously. After 24 hours, the aqueous humor was collected from both eyes, and the number of infiltrating cells, protein concentration, nitric oxide (NO), prostaglandin (PG)-E2, and TNF-alpha levels in the aqueous humor were determined. RAW 264.7 cells treated with various concentrations of ACE were incubated with 10 mug/mL LPS for 24 hours. Levels of NO, PGE2, and TNF-alpha were determined by an enzyme-linked immunosorbent assay. The expression of iNOS and COX-2 proteins was analyzed by Western blot analysis. RESULTS: The number of inflammatory cells, the protein concentrations, and the levels of NO, PGE2, and TNF-alpha in the aqueous humor in the groups treated with ACE were significantly decreased in a dose-dependent manner. In addition, the anti-inflammatory effect of 100 mg ACE was as strong as that of 10 mg prednisolone. The anti-inflammatory action of ACE was stronger than that of either quercetin or anthocyanin administered alone. ACE also suppressed LPS-induced iNOS and COX-2 protein expressions in RAW 264.7 cells in vitro in a dose-dependent manner. CONCLUSIONS: The results suggest that ACE has a dose-dependent anti-ocular inflammatory effect that is due to the direct blocking of the expression of the iNOS and COX-2 enzymes and leads to the suppression of the production of NO, PGE2, and TNF-alpha.
Invest Ophthalmol Vis Sci. 2005 Jan;46(1):275-81