Blueberry Diet Research Articles

Blueberry Prevents the Bladder Dysfunction in Bladder Outlet Obstruction Rats by Attenuating Oxidative Stress and Suppressing Bladder Remodeling.

Various berries demonstrate antioxidant activity, and this effect is expected to prevent chronic diseases. We examined whether a diet containing blueberry powder could prevent the development of bladder dysfunction secondary to bladder outlet obstruction (BOO). Eighteen 8-week-old male Sprague-Dawley rats were randomly divided into three groups: Sham (sham operated + normal diet), N-BOO (BOO operated + normal diet) and B-BOO (BOO operated + blueberry diet). Four weeks after BOO surgery, the N-BOO group developed bladder dysfunction with detrusor overactivity. The B-BOO group showed significantly improved micturition volume and micturition interval. The urinary levels of 8-hydroxy-2′-deoxyguanosine (8-OHdG) and malondialdehyde (MDA) were measured as oxidative stress markers. In the N-BOO group, 8-OHdG increased 1.6-fold and MDA increased 1.3-fold at 4 weeks after surgery, whereas the increase in 8-OHdG was significantly reduced by 1.1-fold, despite a similar increase in MDA, in the B-BOO group. Bladder remodeling was confirmed due to bladder hypertrophy, fibrosis and increased connexin43 expression in the N-BOO group, but these histological changes were reduced in the B-BOO group. The intake of blueberries prevented the development of bladder dysfunction secondary to BOO. This effect seems to be related to antioxidation and the inhibition of bladder remodeling.

Dietary inclusion effect of yacon, ginger, and blueberry on growth, body composition, and disease resistance of juvenile black rockfish (Sebastes schlegeli) against Vibrio anguillarum

BackgroundTo minimize the use of antibiotics and to obtain a more sustainable fish culture and aquaculture industry, development of alternative natural source of immunostimulant to replace antibiotic in aquafeed is highly needed.ObjectiveDietary inclusion effect of yacon (YC), ginger (GG), and blueberry (BB) on growth, body composition, and disease resistance of black rockfish against Vibrio anguillarum was compared to ethoxyquin (EQ).MethodsFour hundred eighty juvenile (an initial weight of 4.2 g) fish were randomly distributed into 12 of 50 L flow-through tanks (forty fish per tank). Four experimental diets were prepared; the control (Con) diet with 0.01% EQ inclusion, and YC, GG, and BB diets at 1% each additive inclusion. Each additive was included into the experimental diets at the expense of wheat flour. Each diet was assigned to triplicate tanks of fish and hand-fed to satiation twice daily for 8 weeks. At the end of 8-week feeding trial, 20 fish from each tank fish were artificially infected by intraperitoneal injection with 0.1 mL of culture suspension of pathogenic V. anguillarum containing 3.3 × 106 cfu/mL respectively. Fish were monitored for the following 8 days after V. anguillarum infection and dead fish were removed every 6 h for the first 4 days and 12 h for the rest of the study.ResultsWeight gain, specific growth rate (SGR), and feed efficiency ratio (FER) of fish fed the YC diet was higher than those of fish fed all other diets. However, feed consumption, protein efficiency ratio, and protein retention was not affected by dietary additive. Moisture, crude protein, and crude lipid content of the whole body of fish were affected by dietary additive. Analysis of the Kaplan-Meier survival curves showed that survival of fish fed the YC, BB, and GG diets was higher than the Con diet.ConclusionOral administration of YC can improve not only weight gain, SGR, and FER of black rockfish, but lower mortality of rockfish at occurrence of V. anguillarum.

배합사료내 야콘, 생강 및 블루베리 첨가에 따른 조피볼락 (Sebastes schlegeli) 치어의 성장, 혈액성상 및 Streptococcus iniae 감염에 미치는 영향

Yacon (YC), ginger (GG) and blueberry (BB) were added to the diet of juvenile rockfish Sebastes schlegeli to investigate the effects of these substances on growth, feed utilization and resistance to Streptococcus iniae compared to feed additive ethoxyquin. A total of 480 fish were distributed in 12 tanks and four experimental diets [control (Con), with 0.01% ethoxyquin, and 1% YC, GG and BB diets] were provided in triplicate. After an 8-week feeding trial, 20 fish from each tank were infected with Streptococcus iniae. Fish fed the BB diet had higher weight gain than fish fed the GG and Con diets. Feed efficiency of fish fed the GG and YC diets was higher than that of fish fed the BB and Con diets. The protein efficiency ratio of fish fed the GG diet was higher than that of fish fed any other diet. The cumulative mortality 54 h after infection of fish fed the Con diet was higher than that of fish fed any other diet. These results indicate that YC, GG, and BB are effective dietary additive, not only improving growth performance and feed utilization but also lowering the mortality of juvenile rockfish exposed to S. iniae.

Neurochemical differences in learning and memory paradigms among rats supplemented with anthocyanin-rich blueberry diets and exposed to acute doses of 56Fe particles

The protective effects of anthocyanin-rich blueberries (BB) on brain health are well documented and are particularly important under conditions of high oxidative stress, which can lead to “accelerated aging.” One such scenario is exposure to space radiation, consisting of high-energy and -charge particles (HZE), which are known to cause cognitive dysfunction and deleterious neurochemical alterations. We recently tested the behavioral and neurochemical effects of acute exposure to HZE particles such as 56Fe, within 24–48h after exposure, and found that radiation primarily affects memory and not learning. Importantly, we observed that specific brain regions failed to upregulate antioxidant and anti-inflammatory mechanisms in response to this insult. To further examine these endogenous response mechanisms, we have supplemented young rats with diets rich in BB, which are known to contain high amounts of antioxidant-phytochemicals, prior to irradiation. Exposure to 56Fe caused significant neurochemical changes in hippocampus and frontal cortex, the two critical regions of the brain involved in cognitive function. BB supplementation significantly attenuated protein carbonylation, which was significantly increased by exposure to 56Fe in the hippocampus and frontal cortex. Moreover, BB supplementation significantly reduced radiation-induced elevations in NADPH-oxidoreductase-2 (NOX2) and cyclooxygenase-2 (COX-2), and upregulated nuclear factor erythroid 2-related factor 2 (Nrf2) in the hippocampus and frontal cortex. Overall results indicate that 56Fe particles may induce their toxic effects on hippocampus and frontal cortex by reactive oxygen species (ROS) overload, which can cause alterations in the neuronal environment, eventually leading to hippocampal neuronal death and subsequent impairment of cognitive function. Blueberry supplementation provides an effective preventative measure to reduce the ROS load on the CNS in an event of acute HZE exposure.

배합사료내 사료첨가제가 조피볼락(Sebastes schlegeli) 치어의 성장, 사료 이용성 및 체조성에 미치는 영향

The effects of dietary supplementing natural additives [yacon (YC), ginger (GG), and blueberry (BB)] on growth, feed utilization, and body composition of juvenile rockfish were compared to those of ethoxyquin (EQ), which is commonly used to prevent rancidity of fish feed. A total of 480 fish were distributed randomly into 12 50-L flow-through tanks (40 fish/tank). Four experimental diets were prepared: the control diet (Con) with 0.01% EQ, and the YC, GG and BB diets containing 1% YC, GG, and BB instead of wheat flour. Each diet was assigned randomly to triplicate tanks of fish, which were hand fed to satiation twice daily for 8 weeks. Weight gain of fish fed the YC diet was higher than that of fish fed all other diets. Feed efficiency (FE), protein efficiency ratio (PER), and protein retention (PR) in fish fed the YC diet were higher than those in fish fed the other diets. Whole-body chemical composition of the fish was affected by the additive sources. In conclusion, dietary supplementation with GG effectively improved weight gain and feed utilization (FE, PER, and PR) of juvenile rockfish.

Wild blueberry consumption attenuates local inflammation in the perivascular adipose tissue of obese Zucker rats

Perivascular adipose tissue (PVAT) has been shown to play important roles in regulating vascular tone and linking local and systemic vascular inflammation. We examined the impact of PVAT on phenylephrine-mediated vasoconstriction in the aorta of obese Zucker rats (OZR) and their lean littermates (LZR) by comparing aortic rings with or without PVAT. Subsequently we placed OZR and LZR on a control (C) or an 8% wild blueberry (WB) diet and evaluated the effect of WB consumption on such response. PVAT-released adipokine concentrations were also measured as a function of WB diet. Maximal constrictor force (Fmax) in aortic rings without PVAT was significantly lower in OZR-C compared with LZR-C (0.41 ± 0.05 and 0.71 ± 0.06 g, respectively). Following WB diet, Fmax significantly increased in OZR (0.54 ± 0.06 g). In aortas with intact PVAT, Fmax was significantly lower in all groups (0.31 ± 0.06 OZR-C, 0.30 ± 0.05 OZR-WB, 0.29 ± 0.03 LZR-C, and 0.30 ± 0.04 g LZR-WB), but no difference was observed between treatments. PVAT concentrations of monocyte chemoactractant protein 1 (MCP-1), tumor necrosis factor alpha, and adiponectin were significantly higher in OZR compared with LZR (+102%, +108%, and +45%, respectively). Following WB diet, PVAT concentrations of interleukin-8 were significantly lower in both OZR (-37%) and LZR (-30%), while adiponectin concentrations significantly increased in both OZR (+11%) and LZR (+16%). MCP-1 concentrations significantly decreased (-31%) in the PVAT of OZR with the WB diet. WB consumption appears to attenuate local inflammation in PVAT, which may impact systemic vascular inflammation and endothelial function.

Blueberry Supplementation Alters Biomarkers of Oxidative Stress in High‐fat Fed Rats

Obesity is associated with enhanced inflammation and oxidative stress. Blueberries contain high levels of anthocyanins, which may mitigate oxidative stress through direct antioxidant activity and/or alterations to antioxidant enzyme activities. Our objective was to determine if blueberry supplementation would decrease systemic, hepatic, and colonic oxidative stress in high fat fed rats. Wistar rats (n= 8/group) were fed low‐fat (LF, 10% fat), high‐fat (HF, 45% fat) or high‐fat with 10% blueberry (HF_BB) diets for 8 wks. HF and HF_BB diets were isocaloric and all diets were matched for sugar and fiber content. Levels of urinary F2‐isoprostanes, a marker of systemic lipid peroxidation, and hepatic and colonic malondialdehyde (MDA) were assessed. Activities of glutathione peroxidase (GPx) and glutathione reductase (GR), antioxidant enzymes that may be altered by anthocyanins, were also measured in liver. Unexpectedly, blueberry supplementation resulted in a small but significant increase in urinary F2‐isoprostanes in high fat fed rats. Hepatic MDA was elevated by HF feeding but was significantly lower in HF_BB fed animals compared to HF fed animals. Blueberry supplementation did not enhance hepatic GPx or GR activities, suggesting these enzymes did not account for the reduction in hepatic MDA. Although colonic MDA was lower in HF_BB animals compared to HF animals, the difference was not significant. These results suggest that blueberry supplementation may alter oxidative stress in high fat fed animals in a tissue‐specific manner.Support or Funding InformationThis material is based on work that is supported by the National Institute of Food and Agriculture, USDA, under award number 2014‐67017‐21757 & GA Agricultural Experiment Station.

Blueberry Diet Derived 3‐(3‐hydroxyphenyl) Propionic Acid (PPA) Suppresses Osteoblastic Cell Senescence to Promote Bone Accretion in Mice

A blueberry (BB) supplemented diet has been previously shown to significantly stimulate bone formation in rapidly growing male and female rodents. Phenolic acids (PAs) are metabolites derived from polyphenols found in fruits and vegetables as a result of the actions of gut bacteria, and the levels of seven individual PAs were found to be at least 10 times higher in the serum of rats fed a BB‐containing diet compared to those fed a control diet. We have characterized the effects of one such BB‐associated serum PA, 3‐(3‐hydroxyphenyl) propionic acid (PPA), on stimulating osteoblastogenesis. To better understand the mechanistic actions of PPA on bone formation, we administered four doses of PPA (0.1, 0.5, 1 and 5 mg/kg/d) to one‐month‐old female C57BL6/J mice for thirty days. We found that stimulation of osteoblast differentiation and proliferation occurred in PPA treated osteoblastic cells. Using peripheral quantitative CT scan (pQCT) and micro‐CT analyses, we demonstrated differences in bone phenotypes between control and PPA‐treated animals, i.e., bone mass was significantly higher in 1 to 5 mg/kg/d PPA‐treated animals compared to controls (p<0.05). Micro‐CT showed bone volume and trabecular number in 1 mg/kg/d treated animals were 0.14±0.007 and 4.76±0.095 versus 0.12±0.02 and 4.33±0.33 in control animals (p<0.05). The bone formation marker alkaline phosphatase in both serum and bone marrow plasma was dose‐dependently increased in PPA‐treated animals. After aspiration of bone marrow, femur bone protein and RNA were isolated for Western blot and real‐time PCR analysis of signaling transduction. We found that PPA was able to suppress bone senescence signaling as evaluated by measuring senescence‐associated beta‐galactosidase activity, PPARγ, p53 and p21 expression (p<0.05 vs control). In conclusion, blueberry‐derived PPA is capable of altering the mesenchymal stem cell differentiation program and bone cell senescence. Thus, PPA or blueberry‐rich diets merit investigation as potential dietary alternatives to drugs for degenerative bone disorders or to promote bone growth during development. Supported in part by USDA‐ARS Project 6026‐51000‐010‐05S.Support or Funding InformationSupported in part by USDA‐ARS Project 6026‐51000‐010‐05S

The beneficial effects of berries on cognition, motor behaviour and neuronal function in ageing.

Previously, it has been shown that strawberry (SB) or blueberry (BB) supplementations, when fed to rats from 19 to 21 months of age, reverse age-related decrements in motor and cognitive performance. We have postulated that these effects may be the result of a number of positive benefits of the berry polyphenols, including decreased stress signalling, increased neurogenesis, and increased signals involved in learning and memory. Thus, the present study was carried out to examine these mechanisms in aged animals by administering a control, 2 % SB- or 2 % BB-supplemented diet to aged Fischer 344 rats for 8 weeks to ascertain their effectiveness in reversing age-related deficits in behavioural and neuronal function. The results showed that rats consuming the berry diets exhibited enhanced motor performance and improved cognition, specifically working memory. In addition, the rats supplemented with BB and SB diets showed increased hippocampal neurogenesis and expression of insulin-like growth factor 1, although the improvements in working memory performance could not solely be explained by these increases. The diverse polyphenolics in these berry fruits may have additional mechanisms of action that could account for their relative differences in efficacy.

Differential effects of blueberry polyphenols on age‐associated neuroinflammation and cognition.

Long-term effects of oxidative stress and inflammatory insults are thought to contribute to the decrements in cognitive performance seen in aging and neurodegenerative diseases. In previous studies, we have shown the beneficial effects of various dark-colored berry fruits in reversing age-related deficits in behavioral and neuronal function when fed to aged rats. However, it is unclear if the benefits of blueberries to brain health are a global phenomenon or if blueberries are more beneficial to only a subset of the population. Because chronic neuroinflammation is believed to be an underlying factor in age-related cognitive decline, it is possible that blueberry supplementation would have differential effects based on baseline cognitive performance. To explore the effect of individual differences on the efficacy of dietary blueberries, aged rats were behaviorally assessed in the radial arm water maze (RAWM) and divided into good, average, and poor learners based on reference (RM) and working memory (WM) errors. Half the rats in each group were then fed a control or a 2% blueberry (BB) diet for 8 weeks, before being re-tested in the RAWM. Latency in the RAWM was significantly (p<0.05) reduced in the BB-fed poor performers from pre- to post-test. WM and RM errors were increased in the control-fed good performers from pre- to post-test, as were RM errors in the BB-fed good performers (p<0.05). Behavioral findings reflect individual rats' neuroinflammatory status. Therefore, daily consumption of blueberries may reverse some age-related deficits in cognition, as well as preserve function among those with intact cognitive ability.

Protective effects of blueberry- and strawberry diets on neuronal stress following exposure to 56Fe particles

Particles of high energy and charge (HZE particles), which are abundant outside the magnetic field of the Earth, have been shown to disrupt the functioning of neuronal communication in critical regions of the brain. Previous studies with HZE particles, have shown that irradiation produces enhanced indices of oxidative stress and inflammation as well as altered neuronal function that are similar to those seen in aging. Feeding animals antioxidant-rich berry diets, specifically blueberries and strawberries, countered the deleterious effects of irradiation by reducing oxidative stress and inflammation, thereby improving neuronal signaling. In the current study, we examined the effects of exposure to 56Fe particles in critical regions of brain involved in cognitive function, both 36h and 30 days post irradiation. We also studied the effects of antioxidant-rich berry diets, specifically a 2% blueberry or strawberry diet, fed for 8 weeks prior to radiation as well as 30 days post irradiation. 56Fe exposure caused significant differential, neurochemical changes in critical regions of the brain, such as hippocampus, striatum, frontal cortex, and cerebellum, through increased inflammation, and increased oxidative stress protein markers. 56Fe exposure altered the autophagy markers, and antioxidant-rich berry diets significantly reduced the accumulation of p62 in hippocampus, a scaffold protein that co-localizes with ubiquitinated protein at the 30 days post irradiation time-point. Exposure to 56Fe particles increased the accumulation of disease-related proteins such as PHF-tau in the hippocampus of animals fed the control diet, but not in the irradiated animals fed the blueberry diet. These results indicate the potential protective effects of antioxidant-rich berry diets on neuronal functioning following exposure to HZE particles.

Detection of Anthocyanins/Anthocyanidins in Animal Tissues

Dietary polyphenols may contribute to the prevention of several degenerative diseases, including cancer. Anthocyanins have been shown to possess potential anticancer activity. The aim of this study was to determine anthocyanin bioavailability in lung tissue of mice fed a blueberry diet (5% w/w) for 10 days or a bolus dose (10 mg/mouse; po) of a native mixture of bilberry anthocyanidins. All five anthocyanidins present in the blueberry were detected in the lung tissue using improved methods. The effect of various solvents on the stability of anthocyanins and their recovery from the biomatrix was analyzed. Detection of anthocyanins and their metabolites was performed by UPLC and LC-MS. Although anthocyanins were not detected, cyanidin was detected by UPLC-PDA and other anthocyanidins were detected by LC-MS, following conversion to anthocyanidins and selective extraction in isoamyl alcohol. The results show that anthocyanins can be detected in lung tissue of blueberry-fed mice and thus are bioavailable beyond the gastrointestinal tract.

Chemopreventive and Therapeutic Activity of Dietary Blueberry against Estrogen-Mediated Breast Cancer

Berries are gaining increasing importance lately for their chemopreventive and therapeutic potential against several cancers. In earlier studies, a blueberry-supplemented diet has shown protection against 17β-estradiol (E2)-mediated mammary tumorigenesis. This study tested both preventive and therapeutic activities of diet supplemented with whole blueberry powder (50:50 blend of Tifblue and Rubel). Animals received 5% blueberry diet, either 2 weeks prior to or 12 weeks after E2 treatment in preventive and therapeutic groups, respectively. Both interventions delayed the tumor latency for palpable mammary tumors by 28 and 37 days, respectively. Tumor volume and multiplicity were also reduced significantly in both modes. The effect on mammary tumorigenesis was largely due to down-regulation of CYP 1A1 and ER-α gene expression and also favorable modulation of microRNA (miR-18a and miR-34c) levels. These data suggest that the blueberry blend tested is effective in inhibiting E2-mediated mammary tumorigenesis in both preventive and therapeutic modes.

Blueberry Supplementation Improves Memory in Middle-Aged Mice Fed a High-Fat Diet

Consuming a high-fat diet may result in behavioral deficits similar to those observed in aging animals. It has been demonstrated that blueberry supplementation can allay age-related behavioral deficits. To determine if supplementation of a high-fat diet with blueberries offers protection against putative high-fat diet-related declines, 9-month-old C57Bl/6 mice were maintained on low-fat (10% fat calories) or high-fat (60% fat calories) diets with and without 4% freeze-dried blueberry powder. Novel object recognition memory was impaired by the high-fat diet; after 4 months on the high-fat diet, mice spent 50% of their time on the novel object in the testing trial, performing no greater than chance performance. Blueberry supplementation prevented recognition memory deficits after 4 months on the diets, as mice on this diet spent 67% of their time on the novel object. After 5 months on the diets, mice consuming the high-fat diet passed through the platform location less often than mice on low-fat diets during probe trials on days 2 and 3 of Morris water maze testing, whereas mice consuming the high-fat blueberry diet passed through the platform location as often as mice on the low-fat diets. This study is a first step in determining if incorporating more nutrient-dense foods into a high-fat diet can allay cognitive dysfunction.

Feeding Blueberry Diets to Young Rats Dose-Dependently Inhibits Bone Resorption through Suppression of RANKL in Stromal Cells

Previous studies have demonstrated that weanling rats fed AIN-93G semi-purified diets supplemented with 10% whole blueberry (BB) powder for two weeks beginning on postnatal day 21 (PND21) significantly increased bone formation at PND35. However, the minimal level of dietary BB needed to produce these effects is, as yet, unknown. The current study examined the effects of three different levels of BB diet supplementation (1, 3, and 5%) for 35 days beginning on PND25 on bone quality, and osteoclastic bone resorption in female rats. Peripheral quantitative CT scan (pQCT) of tibia, demonstrated that bone mineral density (BMD) and content (BMC) were dose-dependently increased in BB-fed rats compared to controls (P<0.05). Significantly increased bone mass after feeding 5% BB extracts was also observed in a TEN (total enteral nutrition) rat model in which daily caloric and food intake was precisely controlled. Expression of RANKL (receptor activator of nuclear factor-κB ligand) a protein essential for osteoclast formation was dose-dependently decreased in the femur of BB animals. In addition, expression of PPARγ (peroxisome proliferator-activated receptor γ) which regulates bone marrow adipogenesis was suppressed in BB diet rats compared to non-BB diet controls. Finally, a set of in vitro cell cultures revealed that the inhibitory effect of BB diet rat serum on RANKL expression was more profound in mesenchymal stromal cells compared to its effect on mature osteoblasts, pre-adipocytes and osteocytes. These results suggest that inhibition of bone resorption may contribute to increased bone mass during early development after BB consumption.

Abstract 3705: Chemopreventive and therapeutic activity of high anthocyanin-content blueberry against estrogen-mediated breast cancer.

Abstract Berries are gaining increasing importance lately for their chemopreventive and therapeutic potential against several cancers in pre-clinical studies. In our earlier studies, blueberry-supplemented diet has shown chemopreventive protection against 17β-estradiol-mediated mammary tumorigenesis. The 5 anthocyanidins in blueberry are presumable bioactives. In this study, we tested both preventive and therapeutic activities of high anthocyanin-content blueberry diet in ACI rat model against 17β-estradiol-mediated mammary tumorigenesis. The blueberry used was a blend of Tifblue and Rubel blueberry (50:50) (U.S. Highbush Blueberry Council, CA) which has substantially higher amount of anthocyanins than Berkley/Blue Jay/Bluecrop blueberries used in our earlier studies. To study the chemopreventive effect, female ACI rats (5-6-week old) were administered AIN-93M diet or diets supplemented with blueberry (2.5 and 5%, w/w) 2 weeks prior to 17β-estradiol implantation. To test for the therapeutic activity, when 5% of the animals in the control group developed palpable tumors, one half of the animals were provided diet supplemented with 5% blueberry while the other half were continued on control diet. Animals received diet and water ad libitum and palpated weekly to determine the effect of berry intervention on tumor latency and tumor growth. When the tumor incidence reached &amp;gt;90% in estrogen-treated group on control diet, all the animals were euthanized. Our data revealed i) the first tumor in control group appeared after 85 days, while this was delayed by 28 and 37 days in groups receiving 5% blueberry in chemopreventive and therapeutic mode, respectively. The effect was less pronounced (delay by 7 days) with 2.5% berry; ii) the tumor incidence was also decreased dose dependently (96% in control versus 85% and 61% with 2.5% and 5% blueberry in chemopreventive mode, 55% with 5% blueberry in therapeutic mode); iii) a 25% and 51% reduction in tumor multiplicity with 2.5% and 5% blueberry, respectively (57% reduction with 5% blueberry in therapeutic mode); and iv) 37% and 45% reduction in tumor volume with 5% blueberry in chemopreventive and therapeutic modes, respectively; the effect with 2.5% blueberry was only modest. These data suggest that the test blueberry is effective in inhibiting estrogen-mediated mammary tumorigenesis in both chemopreventive and therapeutic modes. In view of our recent findings of miRNA ‘signature’ in estrogen-induced mammary tumors and its favorable modulation by ellagic acid, we are analyzing modulation of miRNAs in the current study and its correlation with the tumor inhibition. (Supported by Highbush Blueberry Council, CA, Agnes Brown Duggan Fund and Helmsley Foundation). Citation Format: Jeyaprakash Jeyabalan, Farrukh Aqil, Radha Munagala, Ramesh Gupta. Chemopreventive and therapeutic activity of high anthocyanin-content blueberry against estrogen-mediated breast cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3705. doi:10.1158/1538-7445.AM2013-3705

Wild blueberry (Vaccinium angustifolium) consumption improves inflammatory status in the obese Zucker rat model of the metabolic syndrome

The metabolic syndrome (MetS) is a major public health problem in the United States. Chronic inflammation is a critical component of the MetS, leading to dramatically increased risk of type II diabetes and cardiovascular disease.This study investigates the ability of a wild-blueberry-enriched diet to improve the proinflammatory status associated with MetS in the obese Zucker rat (OZR). Circulating levels of key inflammatory markers and their expression in the liver and abdominal adipose tissue were examined in OZR and its genetic control, the lean Zucker rat (LZR), after feeding a control or an 8% wild blueberry diet (WB) for 8 weeks from age 8 to 16 weeks.In the OZR, WB consumption resulted in decreased plasma concentrations of tumor necrosis factor (TNF)-α (−25.6%, P<.05), interleukin (IL)-6 (−14.9%, P<.05) and C-reactive protein (CRP) (−13.1%, P<.05) and increased adiponectin concentration (+21.8%, P<.05). Furthermore, expression of IL-6, TNF-α and nuclear factor (NF)-kB was down-regulated in both the liver (−65%, −59% and −25%, respectively) and the abdominal adipose tissue (−64%, −52% and −65%), while CRP expression was down-regulated only in the liver (−25%). In the abdominal adipose tissue, similar trends were also observed in LZR following WB treatment, with decreased liver expression of NF-kB, CRP, IL-6 and TNF-α (−24%, −16%, −21% and −50%) and increased adiponectin expression (+25%).Results of this study suggest that wild blueberry consumption exerts an overall anti-inflammatory effect in the OZR, a model of the metabolic syndrome.

Suppression of Wnt1-induced mammary tumor growth and lower serum insulin in offspring exposed to maternal blueberry diet suggest early dietary influence on developmental programming

Despite the well-accepted notion that early maternal influences persist beyond fetal life and may underlie many adult diseases, the risks imposed by the maternal environment on breast cancer development and underlying biological mechanisms remain poorly understood. In this study, we investigated whether early exposure to blueberry (BB) via maternal diet alters oncogene Wnt1-induced mammary tumorigenesis in offspring. Wnt1-transgenic female mice were exposed to maternal Casein (CAS, control) or blueberry-supplemented (CAS + 3%BB) diets throughout pregnancy and lactation. Offspring were weaned to CAS and mammary tumor development was followed until age 8 months. Tumor incidence and latency were similar for both groups; however, tumor weight at killing and tumor volume within 2 weeks of initial detection were lower (by 50 and 60%, respectively) in offspring of BB- versus control-fed dams. Dietary BB exposure beginning at weaning did not alter mammary tumor parameters. Tumors from maternal BB-exposed offspring showed higher tumor suppressor (Pten and Cdh1) and lower proproliferative (Ccnd1), anti-apoptotic (Bcl2) and proangiogenic (Figf, Flt1 and Ephb4) transcript levels, and displayed attenuated microvessel density. Expression of Pten and Cdh1 genes was also higher in mammary tissues of maternal BB-exposed offspring. Mammary tissues and tumors of maternal BB-exposed offspring showed increased chromatin-modifying enzyme Dnmt1 and Ezh2 transcript levels. Body weight, serum insulin and serum leptin/adiponectin ratio were lower for maternal BB-exposed than control tumor-bearing offspring. Tumor weights and serum insulin were positively correlated. Results suggest that dietary influences on the maternal environment contribute to key developmental programs in the mammary gland to modify breast cancer outcome in adult progeny.

Blueberry intervention improves vascular reactivity and lowers blood pressure in high-fat-, high-cholesterol-fed rats

Growing evidence suggests that intake of flavonoid-containing foods may exert cardiovascular benefits in human subjects. We have investigated the effects of a 10-week blueberry (BB) supplementation on blood pressure (BP) and vascular reactivity in rats fed a high-fat/high-cholesterol diet, known to induce endothelial dysfunction. Rats were randomly assigned to follow a control chow diet, a chow diet supplemented with 2 % (w/w) BB, a high-fat diet (10 % lard; 0·5 % cholesterol) or the high fat plus BB for 10 weeks. Rats supplemented with BB showed significant reductions in systolic BP (SBP) of 11 and 14 %, at weeks 8 and 10, respectively, relative to rats fed the control chow diet (week 8 SBP: 107·5 (SEM 4·7) v. 122·2 (SEM 2·1) mmHg, P= 0·018; week 10 SBP: 115·0 (SEM 3·1) v. 132·7 (SEM 1·5) mmHg, P< 0·0001). Furthermore, SBP was reduced by 14 % in rats fed with the high fat plus 2 % BB diet at week 10, compared to those on the high-fat diet only (SBP: 118·2 (SEM 3·6) v. 139·5 (SEM 4·5) mmHg, P< 0·0001). Aortas harvested from BB-fed animals exhibited significantly reduced contractile responses (to L-phenylephrine) compared to those fed the control chow or high-fat diets. Furthermore, in rats fed with high fat supplemented with BB, aorta relaxation was significantly greater in response to acetylcholine compared to animals fed with the fat diet. These data suggest that BB consumption can lower BP and improve endothelial dysfunction induced by a high fat, high cholesterol containing diet.

Inhibition of Estrogen-Mediated Mammary Tumorigenesis by Blueberry and Black Raspberry

We previously demonstrated the protective effects of blueberry (BB) and black raspberry (BRB) supplemented at 2.5% dose in an ACI rat mammary tumor model. Here, we assessed a dose-related alteration in tumor indices with diet supplemented with 5% BB or BRB powder. The diet was well tolerated. Tumor palpation from 12 weeks revealed first tumor appearance by 84 days in the control group, that was delayed by 24 and 39 days with the BB and BRB diets, respectively (p = 0.04). Ellagic acid detected in the plasma of rats fed the BRB diet was in the range of 96.6-294.2 ng/mL. While the BB diet showed better efficacy in reducing mammary tissue proliferation and tumor burden, tumor latency was delayed efficiently by BRB. Furthermore, BB was effective in downregulating CYP1A1 expression, while BRB downregulated ERα expression effectively. Distinct anticarcinogenic effects of the two berries correspond to their distinct phytochemical signatures.