Consumption Of Flavonoid-rich Foods Research Articles

Impact of citrus flavonoid supplementation on inflammation in lipopolysaccharide-induced periodontal disease in mice.

In general, the consumption of flavonoid-rich foods may influence the control/dysregulation of the magnitude and duration of inflammation and oxidative stress, which are known to contribute to multiple pathologies. Information regarding the impact of citrus flavonoid dietary supplementation on periodontal disease is still scarce. Herein, we investigated whether a diet supplemented with eriocitrin and eriodictyol could alter the course of the inflammatory response associated with LPS-induced periodontal disease in mice. Sixty BALB/c mice received a standard diet or a diet supplemented with different concentrations of eriocitrin or eriodictyol. After 30 days of food supplementation, a solution containing LPS from Escherichia coli was injected into the gingival tissues three times per week for four weeks. Neutrophils, mononuclear cells and eosinophils were assessed using a severity analysis system in H&E-stained sections and modified picrosirius red. The activities of myeloperoxidase (MPO), a marker of granulocyte infiltration, and eosinophil peroxidase (EPO) were determined spectrophotometrically. The oxidative damage was determined by measuring the malondialdehyde (MDA) content and anti-oxidative activity through the assessment of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). Interleukin (IL)-1β, TNF-α, and IL-10 were quantified by multiplex immunoassay. Periodontal inflammation was significantly inhibited by citrus flavonoid supplementation, including reduced flatness of the gingival epithelium and chronic and acute inflammatory cell infiltration, as well as loss of connective tissue in the gingival papillae. Both eriocitrin and eriodictyol inhibited gingival IL-1β and TNF-α and increased IL-10 secondary to periodontitis. Significant protection and decreased MPO and EPO activity were detected in the periodontal tissue of citrus flavonoid-treated animals. In comparison with the LPS group, SOD, CAT and GPx activities were increased, while the MDA content was reduced, indicating decreased oxidative damage. These results suggest that a diet supplemented with the citrus flavonoids eriocitrin or eriodictyol may aid in the prevention of periodontitis, representing a potential method to enhance local immunity and host defense.

P3783A higher habitual flavonoid intake is associated with a lower risk of atrial fibrillation

Abstract Background Our understanding of how diet affects future risk of atrial fibrillation (AF) is limited. Evidence suggests that higher habitual intakes of flavonoids, bio-active compounds found in plant-based foods and beverages, lower cardiovascular disease risk, attenuate inflammation, and may have anti-arrhythmic properties. Purpose To investigate the association between flavonoid intake and clinically apparent AF in a large cohort of Danish men and women. Methods Baseline data from 55 634 participants without AF of the Danish Diet, Cancer and Health Study, recruited from 1993 to 1997, were cross-linked with Danish nationwide registries. Flavonoid intake was calculated from validated food frequency questionnaires using the Phenol-Explorer database. Associations between flavonoid intake and AF hospitalisation were examined using restricted cubic splines based on Cox proportional hazards models with adjustments for age, sex, BMI, smoking status, physical activity, alcohol intake, income, and hyperthyroidism. Results After a median [IQR] follow-up of 21 [18–22] years, 6 301 participants were hospitalised with AF. Non-linear associations were observed for total flavonoid intake and for all flavonoid sub-classes. For total flavonoid intake, after adjusting for potential lifestyle confounders and compared to participants in quintile 1 (median intake: 173 mg/day), those in quintile 3 (median intake: 320 mg/day) and quintile 4 (median intake: 494 mg/day) had a significantly lower risk of AF, with hazard ratios (95% CI) of 0.93 (0.87, 0.99) and 0.92 (0.86, 0.98), respectively. Compared to median intake in the lowest quintile, a total flavonoid intake of 1000 mg/day was associated with a lower risk of AF in smokers [0.86 (0.77, 0.96)] but not in non-smokers [0.96 (0.88, 1.05)], a lower risk of AF in high alcohol consumers [>20 g/d: 0.84 (0.75, 0.94)] but not in low-to-moderate alcohol consumers [<20 g/d: 0.97 (0.89, 1.06], a trending lower risk of AF in diabetics [0.76 (0.51, 1.14)] but not in non-diabetics [0.95 (0.89, 1.02)], and a trending lower risk of AF in those with ischaemic heart disease [0.84 (0.65, 1.09)] but not in those without [0.96 (0.89, 1.03), Figure 1]. Figure 1 Conclusion We observed an inverse association between total flavonoid intake and AF, most notably in sub-populations with known lifestyle and disease risk factors for AF. This finding warrants investigation in randomised controlled trials. If confirmed, ensuring the adequate consumption of flavonoid-rich foods, particularly in individuals “at risk”, may be an important strategy to mitigate AF risk. Acknowledgement/Funding The Danish Diet, Cancer, and Health Study was funded by the Danish Cancer Society.

P10 - The Role of the Vascular System in Flavonoid-Induced Cognitive Enhancement

Evidence suggests that dietary phytochemicals, in particular flavonoids, may exert beneficial effects on the central nervous system by protecting neurons against stress-induced injury, by suppressing neuroinflammation and by improving cognitive function. Historically, they were believed to do this via an ability to express classical antioxidant activity in the brain. However, their poor brain bioavailability and extensive metabolism means that this is unlikely. Instead, their actions on the brain appear to be mediated by effects on both the peripheral and cerebro-vascular system that lead to improved blood flow to the brain capable of inducing enhanced activity within specific domains of cognitive function. Such vascular effects may also lead to the activation of critical protein and lipid kinase signalling cascades in the brain, leading to a suppression of neuroinflammation and the promotion of synaptic plasticity. This talk will focus on the acute and chronic effects of flavonoid and flavonoid-rich food intake on human executive function (attention, sustained attentiveness and task responsiveness) and episodic memory and how such effects may be mediated by changes in peripheral and cerebrovascular blood flow, measured using flow-mediated dilatation and fMRI. Through such a mechanism, the consumption of flavonoid-rich foods throughout life holds the potential to limit neurodegeneration and to prevent or reverse age-dependent loses in cognitive performance. In addition, flavonoids may represent important precursor molecules in the quest to develop a new generation of brain enhancing drugs.

Rutin activates the MAPK pathway and BDNF gene expression on beta-amyloid induced neurotoxicity in rats

Flavonoids are present in foods such as fruits and vegetables. A relationship between the consumption of flavonoid-rich foods and prevention of human disease including neurodegenerative disorders has been demonstrated. We assessed the effect of rutin (3,3′,4′,5,7-pentahydroxyflavone-3-rhamnoglucoside) on the mitogen-activated protein kinase (MAPK) pathway, memory retrieval and oxidative stress in rats injected with β-amyloid (Aβ), which is implicated to have an important role in Alzheimer's disease (AD). Aβ was injected bilaterally in the deep frontal cortex of rat brain. Next, rutin and saline were injected (i.p.) for 3 weeks. In comparison to the control group, rutin significantly increased extracellular signal-regulated protein kinase 1 (ERK1), cAMP response element-binding protein (CREB) and brain-derived neurotrophic factor (BDNF) gene expression in the hippocampus of rats. Rutin (100mg/kg) significantly increased memory retrieval compared to the control group. Malondialdehyde (MDA) level in the hippocampus of the rutin group was significantly lower than those in the control group. The content of sulfhydryl groups in the rutin group was higher than that in the control group. The findings show a possibility that rutin may have beneficial effects against neurotoxicity of Aβ on memory in rats.

Effects of rutin on oxidative stress in mice with kainic acid-induced seizure

Flavonoids are present in foods such as fruits and vegetables. Several studies have demonstrated a relationship between the consumption of flavonoid-rich foods and prevention of human disease, including neurodegenerative disorders. We assessed the effect of rutin (quercetin-3-O-rutinoside) on oxidative stress in kainic acid (KA)-induced seizure. Thirty-six BALB/c mice were randomly divided into three groups. In the control group, saline (intra-peritoneal, i.p.) was administered for 7 d, and on the last day, KA (10 mg/kg, i.p.) was injected 30 min after administration of saline. In rutin groups, mice were pretreated with rutin (100 and 200 mg/kg, i.p.) for 7 d, and on the last day, KA (10 mg/kg, i.p.) was injected 30 min after administration of rutin. Subsequently, behavioural changes were observed in mice. Lipid peroxidation and oxidative stress were measured respectively in the early and late phases after KA-induced seizures. Seizure scores in the rutin groups were significantly lower than those in the control group (P < 0.01). Furthermore, rutin dose-dependently inhibited the number of wet-dog shakes (WDS) (P < 0.05). Malondialdehyde level in the hippocampus of the rutin groups was significantly lower than that in the hippocampus of the control group on days 1 and 21 after KA administration. In the rutin groups, the thiol levels observed on day 1 after KA administration were higher than that in the control group (P < 0.01). These results indicate that rutin has potential anticonvulsant and antioxidative activities against oxidative stress in KA-induced seizure in mice.

Neuroinflammation and the APOε genotype: Implications for Alzheimer's disease and modulation by dietary flavonoids and n-3 polyunsaturated fatty acids

Alzheimer's disease (AD) is the most common type of dementia with its pathology considered to be the result of complex interactions between genetic and environmental factors. Amongst a large variety of genes analysed, the APO epsilon genotype, represents the only firmly established common genetic risk factor for dementia, with the APOe4 carriers being at 3–16 fold increased risk of AD. Although, the mechanisms by which APOe genotype impacts on AD progression are not fully understood, recent evidence suggests that a large component of the increased risk associated with an APOe4 genotype is likely to be due to increased neuroinflammation and the subsequent loss of cognitive functions. There is increasing evidence from human epidemiological and rodent studies that the consumption of flavonoid-rich foods and n-3 polyunsaturated fatty acids can beneficially influence normal cognitive function. Investigation of the underlying physiological and molecular mechanisms indicates a positive impact of these dietary components on neurogenesis and neuroinflammation. This review will summarise the evidence of the impact and mechanisms underlying the impact of APOe genotype on dementia and AD and the potential role of dietary flavonoids and n-3 polyunsaturated fatty in modulating neuroinflammation and neurocognitive performances. Examination of molecular targets is suggestive that increased intakes of these dietary components have the potential alone or in an additive fashion to ameliorate the pathological consequences of the APOe4 allele. However research examining the ability of dietary strategies in this large population genotype subgroup is distinctly lacking.

Beyond antioxidants: the cellular and molecular interactions of flavonoids and how these underpin their actions on the brain

The consumption of flavonoid-rich foods and beverages has been suggested to limit the neurodegeneration associated with a variety of neurological disorders and to prevent or reverse normal or abnormal deteriorations in cognitive performance. Flavonoids mediate these effects via a number of routes, including a potential to protect neurons against injury induced by neurotoxins, an ability to suppress neuroinflammation and a potential to promote memory, learning and cognitive function. Originally, it was thought that such actions were mediated by the antioxidant capacity of flavonoids. However, their limited absorption and their low bioavailability in the brain suggest that this explanation is unlikely. Instead, this multiplicity of effects appears to be underpinned by three separate processes: first, through their interactions with important neuronal and glial signalling cascades in the brain, most notably the phosphatidylinositol 3-kinase/Akt and mitogen-activated protein kinase pathways that regulate pro-survival transcription factors and gene expression; second, through an ability to improve peripheral and cerebral blood flow and to trigger angiogenesis and neurogenesis in the hippocampus; third, by their capacity to directly react with and scavenge neurotoxic species and pro-inflammatory agents produced in the brain as a result of both normal and abnormal brain ageing. The present review explores the potential inhibitory or stimulatory actions of flavonoids within these three systems and describes how such interactions are likely to underlie neurological effects.

Plasma Matrix Metalloproteinase (MMP)-9 Levels Are Reduced following Low-Calorie Cranberry Juice Supplementation in Men

Objective: Matrix metalloproteinase (MMP)-9, also known as gelatinase B, is implicated in the development of hypertension and atherosclerotic plaque vulnerability to rupture, an important step in the etiology of cardiovascular diseases. Studies have suggested that flavonoid consumption may be cardioprotective, and its favorable impact on circulating MMP-9 concentrations could partly explain this association. The aim of the present study was to determine the effect of consuming increasing daily doses of low-calorie cranberry juice cocktail (CJC) on plasma MMP-9 concentrations of abdominally obese men.Methods: Thirty men (mean age ± SD: 51 ± 10 years) consumed increasing doses of CJC during 3 successive periods of 4 weeks (weeks 1–4: 125 ml/day, weeks 5–8: 250 ml/day, and weeks 9–12: 500 ml/day). Before the study and after each phase, a series of physical and metabolic variables were measured, including MMP-9.Results: We found that CJC supplementation significantly decreased plasma MMP-9 concentrations (mean ± SEM: −36% ± 9%, p < 0.0005; week 12 vs. baseline) while baseline plasma MMP-9 concentrations strongly correlated with the changes noted over the entire intervention (r = −0.71, p < 0.0001). We also show that the reduction in plasma MMP-9 levels was associated with a change in plasma nitrites/nitrates (NOx) concentration over the entire intervention (r = −0.38, p < 0.05; week 12 vs. baseline). Significant correlations were also noted between changes in plasma MMP-9 levels and those of systolic (r = 0.39, p < 0.05) and diastolic (r = 0.60, p < 0.001) blood pressure during the course of the study (week 12 vs. baseline).Conclusions: Our results show that daily CJC consumption is associated with a decrease in plasma MMP-9 concentrations in abdominally obese men. We hypothesize that polyphenolic compounds from cranberries may be responsible for this effect, supporting the notion that the consumption of flavonoid-rich foods can exert cardioprotective effects.

Flavonoids and brain health: multiple effects underpinned by common mechanisms

The neuroprotective actions of dietary flavonoids involve a number of effects within the brain, including a potential to protect neurons against injury induced by neurotoxins, an ability to suppress neuroinflammation, and the potential to promote memory, learning and cognitive function. This multiplicity of effects appears to be underpinned by two processes. Firstly, they interact with important neuronal signalling cascades leading to an inhibition of apoptosis triggered by neurotoxic species and to a promotion of neuronal survival and differentiation. These interactions include selective actions on a number of protein kinase and lipid kinase signalling cascades, most notably the PI3K/Akt and MAP kinase pathways which regulate pro-survival transcription factors and gene expression. Secondly, they induce peripheral and cerebral vascular blood flow in a manner which may lead to the induction of angiogenesis, and new nerve cell growth in the hippocampus. Therefore, the consumption of flavonoid-rich foods, such as berries and cocoa, throughout life holds a potential to limit the neurodegeneration associated with a variety of neurological disorders and to prevent or reverse normal or abnormal deteriorations in cognitive performance.

The Flavonoid Glycosides, Myricitrin, Gossypin and Naringin Exert Anxiolytic Action in Mice

The consumption of flavonoid-rich foods, in particular fruits and vegetables, has been epidemiologically associated with a reduced risk of heart disease, neurodegenerative disease, cancer and other chronic diseases. Flavonoid glycosides, the main class of flavonoids, have been shown to exert CNS-mediated activities, particularly as sedative-hypnotics, analgesics or both, nevertheless no studies have evaluated these agents in anxiety. This study assessed the potential anxiolytic effect of three flavonoid glycosides, myrcitrin, naringin and gossypin, in the elevated plus maze test (EPM). Myricitrin (1 mg/kg) was effective on the EPM showing a clear anxiolytic effect with no signs of sedation. However, higher doses showed possible sedative and myorelaxation effects. Gossypin and naringin both shared a similar profile, with low doses (1 mg/kg) inducing a robust anxiolytic effect which diminished with increasing doses of the flavonoids. Higher doses of these two flavonoids showed a dramatic increase in the open arm exploration accompanied by a decrease in locomotor activity. Hence, naringin (30 mg/kg) and gossypin (30 mg/kg) induce both anxiolytic and sedative effects. These results suggest that flavonoid glycosides have the potential to exert a range of CNS-mediated biological activities.

The neuroprotective potential of flavonoids: a multiplicity of effects

Flavonoids exert a multiplicity of neuroprotective actions within the brain, including a potential to protect neurons against injury induced by neurotoxins, an ability to suppress neuroinflammation, and the potential to promote memory, learning and cognitive function. These effects appear to be underpinned by two common processes. Firstly, they interact with critical protein and lipid kinase signalling cascades in the brain leading to an inhibition of apoptosis triggered by neurotoxic species and to a promotion of neuronal survival and synaptic plasticity. Secondly, they induce beneficial effects on the vascular system leading to changes in cerebrovascular blood flow capable of causing angiogenesis, neurogenesis and changes in neuronal morphology. Through these mechanisms, the consumption of flavonoid-rich foods throughout life holds the potential to limit neurodegeneration and to prevent or reverse age-dependent loses in cognitive performance. The intense interest in the development of drugs capable of enhancing brain function means that flavonoids may represent important precursor molecules in the quest to develop of a new generation of brain enhancing drugs.

Chronic Dietary Intake of Plant-Derived Anthocyanins Protects the Rat Heart against Ischemia-Reperfusion Injury 3

Consumption of flavonoid-rich foods and beverages is thought to reduce the risk of cardiovascular diseases. Whereas the biological activities of flavonoids have been characterized in vitro, there are no clear experimental data demonstrating that chronic dietary intake and intestinal absorption of flavonoids actually protects the heart against ischemia-reperfusion injury. We tested whether long-term consumption of specific flavonoids (anthocyanins) included in normal food could render the heart of rats more resistant to myocardial infarction. Maize kernels that differed specifically in their accumulation of anthocyanins were used to prepare rodent food in which anthocyanins were either present or absent. Male Wistar rats were fed the anthocyanin-rich (ACN-rich) or the anthocyanin-free (ACN-free) diet for a period of 8 wk. Anthocyanins were significantly absorbed and detected in the blood and urine of only rats fed the ACN-rich diet. In Langendorff preparations, the hearts of rats fed the ACN-rich diet were more resistant to regional ischemia and reperfusion insult. Moreover, on an in vivo model of coronary occlusion and reperfusion, infarct size was reduced in rats that ate the ACN-rich diet than in those that consumed the ACN-free diet (P < 0.01). Cardioprotection was associated with increased myocardial glutathione levels, suggesting that dietary anthocyanins might modulate cardiac antioxidant defenses. Our findings suggest important potential health benefits of foods rich in anthocyanins and emphasize the need to develop anthocyanin-rich functional foods with protective activities for promoting human health.

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Favourable impact of low-calorie cranberry juice consumption on plasma HDL-cholesterol concentrations in men

A low HDL-cholesterol concentration is an independent risk factor for CVD. Studies have suggested that flavonoid consumption may be cardioprotective, and a favourable impact on circulating HDL-cholesterol concentrations has been suggested to partially explain this association. The aim of the present study was to determine the effect of consuming increasing daily doses of low-calorie cranberry juice cocktail (CJC) on the plasma lipid profile of abdominally obese men. For that purpose, thirty men (mean age 51 (SD 10) years) consumed increasing doses of CJC during three successive periods of 4 weeks (125 ml/d, 250 ml/d, 500 ml/d). Before the study and after each phase, we measured changes in physical and metabolic variables. We noted a significant increase in plasma HDL-cholesterol concentration after the consumption of 250 ml CJC/d (+8.6+/-14.0% v. 0 ml CJC/d; P<0.01), an effect that plateaued during the last phase of the study (500 ml CJC/d: +8.1+/-10.0% v. 0 ml CJC/d; P<0.0001). Multivariate analyses revealed that changes in plasma apo A-I (R(2)=48%, P<0.0001) and triacylglycerol (R(2)=16%, P<0.005) concentrations were the only variables significantly contributing to the variation in plasma HDL-cholesterol concentration noted in response to the intervention. No variation was observed in total as well as in LDL and VLDL cholesterol. The present results show that daily CJC consumption is associated with an increase in plasma HDL-cholesterol concentrations in abdominally obese men. We hypothesise that polyphenolic compounds from cranberries may be responsible for this effect, supporting the notion that the consumption of flavonoid-rich foods can be cardioprotective.

Inhibitory Effects of Procyanidin B2 Dimer on Lipid-laden Macrophage Formation

A proteomic analysis of procyanidin B(2) isolated from cocoa against oxidized low-density lipoprotein-induced lipid-laden macrophage formation was performed. Of approximately 400 detected proteins, 12 were differentially expressed as a result of B(2) treatment. They were subsequently identified by liquid chromatography-electrospray ionization-tandem mass spectrometry and the SWISS-PROT database. Further reverse transcriptase-polymerase chain reaction and Western blot analysis revealed that B(2) strongly inhibited arachidonic acid inflammatory reactions, apoptosis, and their coupled mitogen-activated protein kinase and NF-kappaB pathways. To highlight proteins or genes with similar expressed patterns and similarly biological function induced by B(2) in lipid-laden macrophages, a cluster and Kyoto Encyclopedia of Genes and Genomes pathway analysis were performed. The data were mapped to multiple pathways. Further validation of the bioinformatic results revealed that activation of Wnt signaling may contribute to the cardioprotection of B(2). The differentially expressed genes and proteins mentioned above induced by B(2) are through regulating nuclear transcription factors, activating peroxisome proliferator-activated receptor-gamma and inhibiting AP-1 mRNA expressions. These in vitro data help to interpret the beneficial effects of B(2) in reducing the risk of atherosclerosis after consumption of flavonoid-rich foods. Many differentially expressed genes induced by B(2) help to uncover novel targets and may help to target disease interactions in atherosclerosis in the future.

The increase in human plasma antioxidant capacity after apple consumption is due to the metabolic effect of fructose on urate, not apple-derived antioxidant flavonoids

Regular fruit consumption lowers the risk of cardiovascular diseases and certain cancers, which has been attributed in part to fruit-derived antioxidant flavonoids. However, flavonoids are poorly absorbed by humans, and the increase in plasma antioxidant capacity observed after consumption of flavonoid-rich foods often greatly exceeds the increase in plasma flavonoids. In the present study, six healthy subjects consumed five Red Delicious apples (1037 ± 38 g), plain bagels (263.1 ± 0.9 g) and water matching the carbohydrate content and mass of the apples, and fructose (63.9 ± 2.9 g) in water matching the fructose content and mass of the apples. The antioxidant capacity of plasma was measured before and up to 6 h after food consumption as ferric reducing antioxidant potential (FRAP), without or with ascorbate oxidase treatment (FRAP AO) to estimate the contribution of ascorbate. Baseline plasma FRAP and FRAP AO were 445 ± 35 and 363 ± 35 μM trolox equivalents, respectively. Apple consumption caused an acute, transient increase in both plasma FRAP and FRAP AO, with increases after 1 h of 54.6 ± 8.7 and 61.3 = 17.2 μM trolox equivalents, respectively. This increase in plasma antioxidant capacity was paralleled by a large increase in plasma urate, a metabolic antioxidant, from 271 ± 39 μM at baseline to 367 ± 43 μM after 1 h. In contrast, FRAP and FRAP AO time-dependently decreased after bagel consumption, together with urate. Consumption of fructose mimicked the effects of apples with respect to increased FRAP, FRAP AO, and urate, but not ascorbate. Taken together, our data show that the increase in plasma antioxidant capacity in humans after apple consumption is due mainly to the well-known metabolic effect of fructose on urate, not apple-derived antioxidant flavonoids.