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Abstract
Consumption of blueberries has increased rapidly over the past decade, as have the numbers of studies suggesting health benefits. Now the blueberry is a commonly consumed berry in the United States. They are used in jellies, jams, and pies, baked into muffins, and are an ingredient of many other snacks and delicacies or baby foods. The major phytochemicals in blueberries are polyphenols, including anthocyanins, proanthocyanidins, other flavonoids, phenolic acids and stilbene derivatives. A diet rich in fruits and vegetables has long been recognized to reduce the risk of cardiovascular diseases. In recent years, evidence has emerged suggesting that some phytochemicals in plant foods, polyphenols in particular, may be largely responsible for their protective activities against cardiovascular diseases, mainly through antioxidant and antiinflammatory activities. Blueberries are rich in polyphenols and exhibit extremely high antioxidant capacity. They have been implicated in preventing cardiovascular diseases for many years. Recent studies, including animal and human studies, have found the beneficial effects of blueberries in cardiovascular diseases from different aspects: preventing development of atherosclerotic lesions, protecting the myocardium from induced ischemic damage, having positive effects on the course of chronic heart failure, lowering blood pressure and improving selected features of metabolic syndrome and related cardiovascular risk factors. The possible underlying mechanisms included but not limited to reducing oxidation of lipoproteins, improving serum antioxidant status and lipid levels, improving endothelial dysfunction and inhibiting inflammation on the vascular system.
... In addition other polyphenols found in blueberries include phenolic acids (primarily hydroxycinnamic acids) and stilbene derivatives. 11,[15][16][17][18][19] During blueberry ripening all of these subclasses diminish with the exception of the anthocyanins, which appear to increase in synthesis. 11,20 The word anthocyanin is derived from the Greek anthos for flowers and kyanos for blue. ...
... The total content of polyphenols in blueberries ranges from 48 [54] up to 304 mg/100 g of fresh fruit weight (up to 0.3%) [55] and strictly depends on the cultivar [56], growing conditions and maturity [57,58], and its estimation may vary depending on the analytical procedure used [45]. Polyphenols present in blueberries include, i.e., flavonoids, procyanidins (monomeric and oligomeric form) [59], flavonols (i.e., kaempferol, quercetin, myricetin) [56] phenolic acids (mainly hydroxycinnamic acids) and derivatives of stilbenes [60,61]. During the ripening of blueberries, a shift in the pool of total polyphenolic compounds towards anthocyanin synthesis was observed and was in line with a decline in the other individual phenolic components [62], suggesting their important role in terms of the bioactivity of blueberries. ...
Blueberries, besides having commonly-recognized taste properties, are also a valuable source of health-promoting bioactive compounds. For several decades, blueberries have gained in popularity all over the world, and recent years have seen not only an increase in fresh consumption, but also in the importance of blueberries for the processing industry. Blueberry processing mostly consists of freezing and juicing. Recently, more attention has been drawn to dewatering and drying, which are promising areas for developing novel blueberry products. Processing affects each biologically-active compound in a different way, and it is still unknown what changes those compounds undergo at the
molecular level after the application of different processing technologies. This work presents the most recent state of knowledge about the pre-treatment and processing methods applied to blueberries and their influence on the content of biologically-active compounds. The presentation of methods is preceded by a brief overview of the characteristics of the blueberry species, a description of the chemical composition of the fruit and a short note about the main growing areas, production volumes and the management of fruit crops.
... Several groups of polyphenols were found in the blueberries, including anthocyanins, proanthocyanidins, flavones, phenolic acids (PA) and stilbenes [9,10]. They have been shown to be strong antioxidants by various in vitro assays [11][12][13]. ...
Highbush (cultivated) and lowbush (wild) are the two major blueberry species in the US market. Eight phenolic acids were detected and quantified from these two species by HPLC-MS. Chlorogenic acid was found to be the predominant phenolic acid in both species, with 0.44 mg/g fresh weight in lowbush blueberries and 0.13 mg/g fresh weight in highbush blueberries. Total phenolic content in lowbush blueberries is over three times higher than that of highbush blueberries. The phenolic acid mixtures representing those in the two species were prepared by using authentic standards to assess their contribution to total antioxidant and anti-inflammatory activities of the whole berries. Neither lowbush nor highbush blueberry phenolic acid mixture contributed significantly to the total antioxidant capacity of their relevant whole berries measured by oxygen radical absorbance capacity (ORAC). Both phenolic acid mixtures were able to enter the cell and showed in cell antioxidant activities from the cell based antioxidant protection of erythrocytes (CAP-e) assay. Lowbush blueberry phenolic acid mixture was found to show anti-inflammatory activities by inhibiting the nuclear factor-κB (NF-κB) activation and the production of inflammatory cytokines (TNF-α and IL-6) at the high dose.
Despite remarkable progress in treatment of chronic heart failure (CHF) over the last two decades, mortality, personal suffering and cost remain staggering, and effective interventions are still a challenge. Previously we reported that a blueberry-enriched diet (BD) attenuated necroapoptosis and inflammation in periinfarct area in a rat model of myocardial infarction (MI).
To test the hypothesis that BD will attenuate the course of CHF, including mortality and cardiac remodeling during the first year after induction of MI in rats.
Two weeks after coronary artery ligation, rats were divided into two groups of similar average MI size, measured by echocardiography, and then 12-mo dietary regimens were initiated as follows: ad libitum regular diet (control, CD, n = 27) and isocaloric food with 2% blueberry supplement (BD, n = 27) also available ad libitum. These dietary groups were compared to each other and to sham group (SH). Mortality over the 12 mo was reduced by 22% in BD compared with CD (p<0.01). In the course of developing CHF, BD had no effect on the body weight, heart rate or blood pressure. Bi-monthly Echo revealed significant attenuation of the LV chamber remodeling, LV posterior wall thinning, and MI expansion in BD compared with CD. In fact, BD arrested the MI expansion.
This is the first experimental evidence that a blueberry-enriched diet has positive effects on the course of CHF and thus warrants consideration for clinical evaluation.
A scheme for the fractionation of flavonoid and nonflavonoid compounds is presented. The phenolic compounds of Highbush blueberries (cultivar ‘Coville’) were analysed by high performance liquid chromatography and thin-layer chromatography. Fifteen anthocyanins were identified as the 3-monoglucoside, 3-monogalactoside and 3-monoarabinoside of delphinidin, cyanidin, malvidin, peonidin and petunidin. No acyl anthocyanin was detected. Derivatives of malvidin and delphinidin were the most abundant; the 3-monogalactoside constituted 41% of the anthocyanin. Four flavonol glycosides were also identified as the kaempferol-3-O-glucoside, 3-O-glucoside, 3-O-galactoside and 3-O-rhamno-side of quercetin. The major phenolic acid was chlorogenic acid. After hydrolysis of the phenolic neutral fraction (FA), gallic, syringic and vanillic acids were identified by TLC. These acids appeared to be present in their ester forms, probably as glucoside esters.
A great many epidemiological studies indicate that a diet rich in flavonoids from vegetables and fruits intake appear to be inversely related to coronary heart disease (CHD) and cancers mortality. Regular moderate consumption of wine can contribute to this phenomenon. Flavonoids in wine and food have been shown to be antioxidant and anti-aggregant in vitro and could indeed help protect against coronary disease. Thus, flavonoids may partly explain the protective effects of the Mediterranean diet, rich in vegetable, fruit and wine against CHD or cancers.
The effect of allyl isothiocyanate (AITC) on antioxidant enzyme activities, flavonoid content, and fruit quality of blueberries var. Duke (Vaccinium corymbosum L.) was evaluated. Results from this study showed that AITC was effective in maintaining higher amounts of sugars and lower organic acids compared to untreated fruit during storage at 10 °C. However, AITC reduced antioxidant enzyme activities [superoxide dismutase (SOD), guaiacol peroxidase (G-POD), glutathione-peroxidase (GSH-POD), ascorbate peroxidase (AsA-POD), dehydroascorbate reductase (DHAR), monodehydroascorbate reductase (MDAR) and glutathione reductase (GR)] and non-enzyme components, ascorbate (AsA) and glutathione (GSH). AITC treatments also reduced the amount of phenolic acids (chlorogenic acid, myricetin 3-arabinoside, quercetin 3-galactoside, quercetin 3-arabinoside, and kaempferol 3-glucoside) and anthocyanins (delphinidin 3-galactoside, delphinidon 3-glucoside, delphinidin 3-arabinoside, petunidin 3-galactoside, petunidin 3-glucoside, petunidin 3-arabinoside, malvidin 3-galactoside, and malvidin 3-arabinoside) during storage at 10 °C. The results from this study indicate that AITC does not promote antioxidant property or scavenge constitutive reactive oxygen species (ROS), but maintain blueberry fruit quality through other mechanisms.
The effect of a wild blueberry-enriched diet on vasoconstriction and vasorelaxation was examined in the adult, 20-week-old spontaneously hypertensive rat (SHR) after 8 weeks of a control (C) or an 8% wild blueberry (WB) diet. Nitric oxide (NO)- and cyclooxygenase (COX)-mediated aortic responses were examined ex vivo with the agonists L-phenylephrine (Phe) and acetylcholine (Ach), in the absence or presence of the NO synthase (NOS) inhibitor L-NG-monomethyl arginine (L-NMMA) or the COX inhibitor mefenamic acid (MFA). The vasoconstriction elicited by Phe was reduced in the WB group, attributed to the NO pathway, favoring a lower vascular tone under basal conditions. Acetylcholine-induced vasorelaxation in the WB group was possibly mediated through the COX, but not the NO pathway. These findings document the potential of wild blueberries to modify major pathways of vasomotor control and improve the vascular tone in the adult SHR with endothelial dysfunction.
Glycosaminoglycans were extracted from the intima and media layers of normal human thoracic aortas from donors of different ages. The arterial segments were devoid of macroscopically visible lesions obtained from patients who had no clinically evident cardiovascular disease. Total glycosaminoglycan content increases during the first 40 years of life. Changes in the content of hyaluronic acid and heparan sulfate are less noticeable. The content of chondroitin sulfate (mainly the 6-isomer) increases, whereas dermatan sulfate remains constant. Plasma LDL-affinity chromatography of dermatan sulfate+chondroitin 4/6-sulfate fractions allowed the separation of LDL high- and low-affinity glycosaminoglycan species. Remarkably, only glycosaminoglycan species with low affinity for plasma LDL increase with age in the disease-free areas of human thoracic aortas studied. These results suggest that age-related changes in glycosaminoglycan composition of the arterial wall do not contribute to increased deposition of plasma LDL. However, the alternative explanation that individuals with arterial glycosaminoglycans that avidly bind LDL would develop early and severe cardiovascular disease and would thus be excluded from our analysis cannot be ruled out.
Carbohydrates are integral components of structural glycoproteins, proteoglycans, immunoglobulins, cell-adhesion and recognition molecules, lectins, transport proteins, cytoplasmic proteins, nucleoproteins, and hormones. The great heterogeneity of carbohydrates, due to the variable number of monosaccharides present in oligo- and polysaccharides, the anomericity and the position of the glycosidic linkage, as well as the branching and the substitution of hydroxyl and amino groups with sulfate, phosphate, or acetyl groups, results in a broad range of structural diversity and biological activity as compared with proteins and nucleic acids. Recent advances on the structure-function relationship have revealed the importance of carbohydrates in vivo, whereas data on their role in biological systems have expanded the classical sciences of biology and biochemistry and opened new areas in diagnosis, treatment, and prognosis. This communication highlights some general principles and concepts of glycobiology with reference to the importance of glycosylation in normal control mechanisms, cancer, host-pathogen interactions, and bacterial infections. Proteoglycans are considered to be the major family of structural glycoconjugates. They are heavily glycosylated and highly charged macromolecules consisting of glycosaminoglycan (GAG) and oligosaccharide chains covalently bound to a protein core. Aggregates of the cartilage PGs with hyaluronan (HA) contribute to the load-bearing properties of cartilage. PGs are essential extracellular components of connective tissues, and most of them have been studied therein, but recent advances have identified new families of much smaller cell surface PGs (Kjellen and Lindahl, 1991). Via specific interactions of GAGs with matrix effector molecules, such as growth factors and/or membrane receptors, PGs participate in several cellular events, such as cell proliferation, differentiation, adhesion, and migration, acting either directly on cells or modulating growth factor activities. We have shown that PGs, via their GAGs, affect cell proliferation and differentiation in human malignant mesothelioma (HMM) cells and that the intracellular signaling process is mediated through a tyrosine phosphokinase activity which requires the interaction of GAGs with growth factors and their receptor (Tzanakakis et al., 1995, 1997). Recently developed HPLC and capillary electrophoresis methods for GAG analysis and structural characterization have also helped in the diagnosis of HMM in pleural effusions and exfoliation syndrome of the eye (Karamanos et al., 1994a, 1997a; Lamari et al., 1998) and to explain that the GAG sequence is nonrandom and biosynthetically regulated (Karamanos et al., 1995) as well as elucidating the biological and physiological properties of GAGs (Karamanos et al., 1994b). Cell surface glycoconjugates play a major role in cell-cell and cell-molecule recognition events. In many cell adhesion molecules of the, nervous system, the peripheral glycoprotein (PO), which is the smallest member of the immunoglobulin superfamily, is involved in critical steps of the pathogenesis of nerve diseases, such as multiple sclerosis. The N-linked oligosaccharides of PO contain the L2/HNK-1 epitope (3-sulfoglucuronic acid). The absence of this epitope results in the failure of cellular aggregation (Filbin and Weissmann, 1991). We found the HNK-1 epitope to be present in invertebrate PGs and we have developed both immunological and HPLC methods for its identification (Karamanos et al., 1994c). Mucins make up another category of GPs with protective effects. They are secreted by the mucosal cells (gastrointestinal, respiratory, and genitourinary). Mucins have molecular weights greater than one million daltons and more than 80% of their dry weight is O-linked carbohydrates which are heavily sialylated and/or sulfated. Mucins lubricate and protect the mucosal epithelium reducing pathogen adhesion to epithelial surfaces. Secreted mucins which bind to pathogens may cover antigenic epitopes, blocking normal antibody response. It is clear that changes in mucin carbohydrates are associated with disease and with susceptibility to infection. Such changes are useful diagnostic markers for a variety of cancers. Thus, the presence of sialylated tumor-related mucin correlates with malignant and metastatic potential. In this area we have developed sensitive methodology to determine the two main sialic acid types (Neu5Ac and Neu5Gc) (Karamanos et al., 1990). Investigation to establish whether these sialic acids may help as an important tumor marker is in progress. The significance of glycosylation in normal control mechanisms may be seen from many known GPs where changes in the carbohydrates are consistently associated with disease development. The tissue plasminogen activator (t-PA) is a serine protease that contributes to the conversion of plasminogen to plasmin. T-PA is very useful in dissolving blood clots in heart attacks and strokes, and the rate of plasminogen activation depends on the presence in oligosaccharides of Asn-184 (Wittwer, 1989). Glycoconjugates are also involved in host-pathogen interactions and bacterial infections. Thus, viral GPs are synthesized by host cells with glycosylation not distinguishable from those of host GPs. Hepatitis B, influenza viruses, and HIV virus all contain such GPs. In HIV virus, GPs are highly N-glycosylated (20-25 potential glycosylation sites) and particularly in gp 120 the carbohydrate content amounts to 50% of the total weight. These glycoconjugates in the surface of parasitic protozoa play a critical role in immune evasion, complement resistance, parasitic internalization, and differentiation. Because of their unique glycan structures, distinct from the host, they may constitute easy targets for drug therapy and vaccine development. In the area of bacterial infections, recent studies have shown that the major components of the extracellular slime layer of S. epidermidis are composed of discrete glycoconjugates. The main polysaccharide component can be used to identify the infection in hospitalized immunocompromised patients (Karamanos et al., 1991b). The correlation of glycosylation with disease can be seen from the increasing number of clinical diagnostic procedures based on the use of lectins to detect abnormal glycosylation on the surface of malignant cells, and the development of anticancer agents which inhibit the glycosylation process. The increase of agalactosyl IgG (Fc N-glycan lacking terminal galactose) in the total IgG correlates with increased disease activity in a number of diseases, such as rheumatoid arthritis and Crohn's disease.
Weanling male Sprague-Dawley rats were randomly fed a control diet (AIN-93) (C) or a blueberry diet (B) for 13 weeks, or a reverse diet (R) (C diet for 13 weeks, switched to the B diet for 8 weeks). Aortas were excised, and two intact and two endothelium-denuded rings were immersed in tissue baths containing physiological salt solution at 37 degrees C and aerated with 95% O(2) and 5% CO(2) (pH 7.4). Following equilibration and preconditioning under 1.5-g preload, cumulative dose-response curves were generated with six doses of the alpha1-adrenergic receptor-selective agonist L-phenylephrine (L-Phe, 10(8)-3 x 10(-6) M) and relaxed with one dose of acetylcholine (3 x 10(-6) M) to assess intact endothelium. The maximum force of contraction (Fmax) and vessel sensitivity (pD(2)) were determined in intact and endothelium-denuded rings. A two-way analysis of variance test revealed that blueberry-fed animals (B and R diets) developed a significantly lower F (max) (0.873 +/- 0.0463 and 0.9266 +/- 0.0463 g, respectively) when contracted with L-Phe, compared with the animals on the C diet (1.109 +/- 0.0463 g) (P < .05). The pD(2) of the intact rings was not significantly different among diet groups. Additionally, diet did not significantly affect the mean F (max) or pD(2) of endothelium-denuded rings. Our results indicate for the first time that wild blueberries incorporated into the diet affect the vascular smooth muscle contractile machinery by suppressing the alpha1-adrenergic receptor agonist-mediated contraction while having no effect on membrane sensitivity of the endothelial or vascular smooth muscle cell layer. Furthermore, their mechanism of action seems to be accomplished through an endothelium-dependent pathway.
It has been documented that increased intake of polyphenols may provide protection against coronary heart disease and stroke. Blueberries (Vaccinium angustifolium) are one of the richest sources of antioxidants among fruits and vegetables. Phenolic compounds from berry extracts inhibit human low density lipoprotein and liposome oxidation. Glycosaminoglycans (GAGs) and proteoglycans (PGs) are structural components of aortas with great structural diversity. Their interaction with compounds such as enzymes, cytokines, growth factors, proteins and lipoproteins and their subsequent role in degenerative diseases has been documented. We investigated the effects of a diet rich in blueberries on the content and structure of GAGs. Sprague-Dawley rats were fed either a control (C) or a blueberry (B) diet for 13 weeks. Aortic tissue GAGs were isolated with papain digestion, alkaline borohydride treatment and anion-exchange chromatography. Cellulose acetate electrophoresis and treatment of the fractions with specific lyases revealed the presence of three GAG populations, i.e. hyaluronan (HA), heparan sulfate (HS) and galactosaminoglycans (GalAGs). Disaccharide composition was determined by high-performance capillary electrophoresis following enzymatic degradation. A 13% higher amount of total GAGs in aortas of B-fed rats was attributed to a higher content of GalAGs (67%). Determination of the sulfated disaccharides showed an overall lower concentration of oversulfated disaccharides in both HS and GalAG populations in the aortas of the B group. Our results demonstrate for the first time that a diet rich in blueberries results in structural alterations in rat aortic tissue GAGs. These changes may affect cellular signal transduction pathways and could have major consequences for the biological function of GAG molecules within the vascular environment.
Oxidation of low-density lipoprotein (LDL) is thought to contribute to atherosclerosis and cardiovascular disease. Consistent with this idea, the antioxidant drug probucol reduces the risk of restenosis, a form of cardiovascular disease, in humans. However, a new study now suggests that the protective effect of probucol depends not on its ability to inhibit lipid oxidation, but on its ability to induce the stress-induced antiinflammatory enzyme heme oxygenase (HO)-1. This might explain why other antioxidants, such as vitamin E, fail to prevent cardiovascular disease in humans.
Dietary recommendations are a key element in the management of cardiovascular disease. Evidence is mounting that certain dietary patterns can influence cardiovascular health by modifying risk factors such as obesity, dyslipidemia, and hypertension, as well as factors involved in systemic inflammation, insulin sensitivity, oxidative stress, endothelial function, thrombosis, and cardiac rhythm. 1,2 In recent years, numerous dietary fads have emerged, in part as a response to the rising prevalence of obesity in the United States. 3 In the present study, we review the various dietary portfolios that have emerged in the literature and the major studies that investigated their effectiveness in modifying cardiovascular risk.