Antioxidant Flavonoids: Structure, Function and Clinical Usage
Alan L. Miller, ND Abstract
Flavonoids occur in most plant species, and account for a significant percentage of the chemical constituents of some; e.g. dried green tea leaves contain approximately 30% flavonoids by weight. Flavonoids have been shown to have antibacterial, anti-inflammatory, antiallergic, antimutagenic, antiviral, antineoplastic, anti-thrombotic, and vasodilatory activity. The potent antioxidant activity of flavonoids—their ability to scavenge hydroxyl radicals, superoxide anions, and lipid peroxy radicals—may be the most important function of flavonoids, and underlies many of the above actions in the body. Oxidative damage is implicated in most disease processes, and epidemiological, clinical, and laboratory research on flavonoids and other antioxidants suggest their use in the prevention and treatment of a number of these. Catechin and its derivatives, oligomeric proanthocyanidins, quercetin and quercetin chalcone, Ginkgo flavone glycosides, silymarin, and others can be utilized in preventative and treatment protocols for cardiovascular disease, cancer, inflammatory conditions, asthma, periodontal disease, liver disease, cataracts and macular degeneration.
Source: Alternative Medicine Review 1996 (Jul); 1 (2): 103–111 http://www.chiro.org/nutrition/ABSTRACTS/Antioxidant_Flavonoids.shtml
Pure dietary flavonoids quercetin and (–)epicatechin augment nitric oxide products and reduce endothelin-1 acutely in healthy men
Wai Mun Loke, Jonathan M Hodgson, Julie M Proudfoot, Allan J McKinley, Ian B Puddey and Kevin D Croft Dietary flavonoids may improve endothelial function and ultimately lead to beneficial cardiovascular effects. The objective was to assess whether pure dietary flavonoids can modulate nitric oxide and endothelin-1 production and thereby improve endothelial function. A randomized, placebo-controlled, crossover trial in 12 healthy men was conducted to compare the acute effects of the oral administration of 200 mg quercetin, (–)-epicatechin, or epigallocatechin gallate on nitric oxide, endothelin-1, and oxidative stress after nitric oxide production was assessed via the measurement of plasma Snitrosothiols and plasma and urinary nitrite and nitrate concentrations. The effects on oxidative stress were assessed by measuring plasma and urinary F2-isoprostanes. Plasma and urinary concentrations of quercetin, (–)-epicatechin, and epigallocatechin gallate were measured to establish the absorption of these flavonoids. Relative to water (control), quercetin and (–)-epicatechin resulted in a significant increase in plasma Snitrosothiols, plasma nitrite, and urinary nitrate concentrations (P < 0.05), but not in plasma nitrate or urinary nitrite. Epigallocatechin gallate did not alter any of the measures of nitric oxide production. Quercetin and (–)-epicatechin resulted in a significant reduction in plasma endothelin-1 concentration (P < 0.05), but only quercetin significantly decreased the urinary endothelin-1 concentration. None of the 3 treatments significantly changed plasma or urinary F2-isoprostane concentrations. Significant increases in the circulating concentrations of the 3 flavonoids were observed (P < 0.05) after the corresponding treatment. Dietary flavonoids, such as quercetin and (–)-epicatechin, can augment nitric oxide status and reduce endothelin-1 concentrations and may thereby improve endothelial function.
Flavonoids From Argentine Tagetes (Asteraceae) With Antimicrobial Activity
María L. Tereschuk, Mario D. Baigorí, Lucia I. C. de Figueroa, Lidia R. Abdala
ABSTRACT The flavonoids, constituting one of the most numerous and widespread groups of natural plant constituents, are important to humans not only because they contribute to plant colors but also because many members are physiologically active. These lowmolecular-weight substances, found in all vascular plants, are phenylbenzopyrones. Over 4000 structures have been identified in plant sources, and they are categorized into several groups Primarily recognized as pigments responsible for the autumnal burst of hues and the many shades of yellow, orange, and red in flowers and food, the flavonoids are found in fruits, vegetables, nuts, seeds, stems, flowers, and leaves as well as tea and wine and are important constituents of the human diet . They are prominent components of citrus fruits and other food sources. Flavonols (quercetin, myricetin, and kaempferol) and flavones (apigenin and luteolin) are the most common phenolics in plantbased foods. Quercetin is also a predominant component of onions, apples, and berries. Such flavanones as naringin are typically present in citrus fruit, and flavanols, particularly catechin, are present as catechin gallate in such beverages as green or black tea and wine. Some major sources of flavonoids are outlined in Table 1 (2). The daily intake of flavonoids in humans has been estimated to be approx 25 mg/d, a quantity that could provide pharmacologically significant concentrations in body fluids and tissues, assuming good absorption from the gastrointestinal tract (3).
Book Title: Public Health Microbiology: Methods and Protocols Series: Methods in Molecular Biology | Volume: 268 | Pub. Date: May-20-2004 | Page Range: 317-330 | DOI: 10.1385/1-59259-766-1:317
To investigate the effects of flavonoid-rich dark chocolate on endothelial function. Amanda Browne. blood pressure. body weight or BMI were seen. 1. PhD. MD Dark chocolate derived from the plant (Theobroma cacao) is a rich source of flavonoids. BS. blood pressure. Engler.4 ± 18.5 nmol/L. 8-isoprostanes. BS. Cardioprotective effects including antioxidant properties. Plasma epicatechin concentrations were markedly increased at 2 weeks in the highflavonoid group (204. p 0. Flavonoid-rich dark chocolate improves endothelial function and is associated with an increase in plasma epicatechin concentrations in healthy adults.5%) (p = 0. 46 mg epicatechin) or low-flavonoid dark chocolate bars (46 g. lipid parameters.99). No significant differences were noted in the resistance to LDL oxidation. Marguerite M.001) but not in the low-flavonoid group (17. and activation of endothelial nitric oxide synthase have been ascribed to the cocoa flavonoids. Paul. lipid profiles. MS. PhD. PhD. Chung Y.Flavonoid-Rich Dark Chocolate Improves Endothelial Function and Increases Plasma Epicatechin Concentrations in Healthy Adults
Mary B. Chiu. measures of oxidative stress. and blood pressure in healthy adult subjects. MD. Mietus-Snyder. double-blind. Engler. MS. The study was a randomized. p = 0. Malloy. PhD.96 ± 0. PhD. body weight or body mass index (BMI) between the two groups.5 ± 9 nmol/L. PhD. Chen.
. Elisa Y. Ho-Kyung Kwak. FACN and Michele L. Mary J. Paul Milbury.3 ± 0. Jeffrey Blumberg. inhibition of platelet activity.7%) as compared to low-flavonoid chocolate consumption (mean change = –0. High-flavonoid chocolate consumption improved endothelium-dependent flow-mediated dilation (FMD) of the brachial artery (mean change = 1.024). Steven M. blood lipids.6 oz). No changes in oxidative stress measures. placebo-controlled design conducted over a 2 week period in 21 healthy adult subjects. total antioxidant capacity. Subjects were randomly assigned to daily intake of high-flavonoid (213 mg procyanidins.
such as luteolin and apigenin. Here. The activation of Cdk5 attenuated PXR-mediated CYP3A4 expression whereas its downregulation enhanced it. but the underlying mechanism of action is unknown. The Cdk kinase profiling assay showed that apigenin inhibits multiple Cdks. In a cell-based screen designed to identify compounds that activate PXR-mediated CYP3A4 gene expression in HepG2 human carcinoma cells.g. Flavonoids. The Cdk5-mediated downregulation of CYP3A4 promoter activity was restored by flavonoids. inhibiting Cdks). suggesting that flavonoids activate PXR by inactivating Cdk5. including the cyclin-dependent kinase (Cdk) pathway.Flavonoids activate pregnane X receptor-mediated CYP3A4 gene expression by inhibiting cyclindependent kinases in HepG2 liver carcinoma cells
Hanqing Dong. Jing Wu. 11:23doi:10. have been shown to modulate various signaling pathways (e. commonly consumed by humans as dietary constituents. suggesting that several Cdks may be involved in activation of PXR by flavonoids.. These results may have important implications on the pharmacokinetics of drugs coadministered with herbal remedy and herbal-drug interactions. suggesting that an alternative mechanism may be responsible for flavonoid-mediated PXR activation. we identified several flavonoids. Consistent with the Cdk5-inhibitory effect of flavonoids. Flavonoids have also been shown to induce CYPs expression. Cdk5 and p35 (a non-cyclin regulatory subunit required to activate Cdk5) were expressed in HepG2. through a PXR-mediated mechanism. which is modulated by numerous signaling pathways. Wenwei Lin. Taosheng Chen
The expression of the drug-metabolizing enzyme cytochrome P450 3A4 (CYP3A4) is regulated by the pregnane X receptor (PXR). The flavonoids did not directly bind to PXR. we report the mechanism responsible for flavonoid-mediated PXR activation and CYP expression. as PXR activators.1186/1471-2091-11-23 Published: 16 June 2010
. Our results for the first time link the stimulatory effect of flavonoids on CYP expression to their inhibitory effect on Cdks. In vitro kinase assays showed that Cdk5 directly phosphorylates PXR. BMC Biochemistry 2010.
suggesting that the antioxidant activity is a result of a combination of different compounds having synergic and antagonistic effects. the samples cited above plus red guava gave inhibition values >70%. In the beta-carotene bleaching system. Gala apple peel. vitamin C. the neutral and acidic flavonoids of red cabbage. The anthocyanin-rich samples showed the highest. There was no relationship between total phenolics content. ABSTRACT Fruits. vegetables. Genovese MI. mulberry FP.
Hassimotto NM. and commercial frozen fruit pulps. at both 10 and 50 microM gallic acid equivalent (GAE) addition levels. Lajolo FM. mulberry. and antioxidant activity. vegetables. acai FP. one that determines the inhibition of copper-induced peroxidation of liposome and another based on the inhibition of the co-oxidation of linoleic acid and beta-carotene. jambolao. some samples showed prooxidant activity in the liposome system coincident with a low antioxidant activity in the beta-carotene system. In the liposome system. antioxidant activities in both systems. PMID: 15826041 PubMed
. On the other hand. black bean. red lettuce. and the acidic flavonoids of acerola FP showed the highest antioxidant activities (>85% inhibition). concentration-dependent. and commercial frozen pulps (FP) consumed in the Brazilian diet were analyzed for antioxidant activities using two different methods.Antioxidant activity of dietary fruits.
especially in autumn. olive oil. Chithan Kandaswami and Theoharis C. Certain plants and spices containing flavonoids have been used for thousands of years in traditional Eastern medicine. They are rich in seeds. They are low molecular weight compounds composed of a three-ring structure with various substitutions. Western medicine has not yet used flavonoids therapeutically. In spite of the voluminous literature available. Jr. however. Suggestions are made where such possibilities may be worth pursuing.. and red wine. and Cancer
. These characteristics appear to also be required for best activity. citrus fruits. The particular hydroxylation pattern of the B ring of the flavonoles increases their activities. Heart Disease. especially antioxidant and antiproliferative. or a hydroxyl group in position 3 of the C (middle) ring. Flavonoids can be subdivided according to the presence of an oxy group at position 4. even though their safety record is exceptional. This basic structure is shared by tocopherols (vitamin E).Mammalian Cells: Implications for Inflammation. especially in inhibition of mast cell secretion. Theoharides ABSTRACT Flavonoids are nearly ubiquitous in plants and are recognized as the pigments responsible for the colors of leaves. a double bond between carbon atoms 2 and 3. in the systems studied. tea.
82) and 0.44 to 1. Ritva Jarvinen.32) and 0. serum cholesterol concentration. Jouni Maatela ABSTRACT
Objective: To study the association between dietary intake of flavonoids and subsequent coronary mortality. The corresponding values for men were 0. respectively. The corresponding values for onions were 0. respectively. presented similar associations. Results: In women a significant inverse gradient was observed between dietary intake of flavonoids and total and coronary mortality.30 to 0.09) for women and men. respectively.53 to 1. Intakes of onions and apples.63 to 0.78 (0. the main dietary sources of flavonoids. Adjustment for intake of antioxidant vitamins and fatty acids weakened the associations for women. The relative risks between highest and lowest quarters of flavonoid intake adjusted for age. Antti Reunanen. smoking.87) for total and coronary mortality.53 to 0.74 (0.Flavonoid intake and coronary mortality in Finland: a cohort study
Paul Knekt.08). respectively. .91) and 0. and body mass index were 0.73 (0. total mortality. and Incidence of Stroke
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. Subjects: 5133 Finnish men and women aged 30-69 years and free from heart disease at baseline.90) and 0. blood pressure.76 (0.61 to 1.36 to 0.93) and 0. and coronary mortality. Antioxidant Vitamins.33 to 0. The relative risks for coronary mortality between highest and lowest quarters of apple intake were 0.
Dietary Flavonoids. Design: A cohort study based on data collected at the Finnish mobile clinic health examination survey from 1967-72 and followed up until 1992.81 (0. respectively.54 (0. Conclusion: The results suggest that people with very low intakes of flavonoids have higher risks of coronary disease.69 (95% confidence interval 0.02). Main outcome measure: Dietary intake of flavonoids.41 to 1.67 (0.56 to 1.00) in women and men.57 (0. the relative risks for coronary heart disease were 0.50 (0. Settings: 30 communities from different parts of Finland.
The RR for a daily consumption of 4. 0.Sirving O. 95% CI. PhD.6 cups of tea was 0. systolic blood pressure. cigarette smoking. Mean nutrient and food intake was calculated from crosscheck dietary histories taken in 1960. Results Forty-two cases of first fatal or nonfatal stroke were documented. A lower stroke risk was also observed for the highest quartile of β-carotene intake (RR.6 mg/d vs <18. Black tea contributed about 70% to flavonoid intake. The intake of vitamin C and vitamin E was not associated with stroke risk. 0.27 (95% confidence interval [CI].22 to 1. The relative risk (RR) of the highest vs the lowest quartile of flavonoid intake ( 28. The association between antioxidants. Keli. energy intake. The hypothesis that dietary antioxidant vitamins and flavonoids account for this observation is investigated in a prospective study.31 (95% CI.
(Arch Intern Med. 0. Adjustment was made for confounding by age. serum cholesterol.154:637-642)
Effect of Acute and Chronic Tea Consumption on Platelet Aggregation in Patients With Coronary Artery Disease
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. selected foods. 0.70). 1965.11 to 0.3 mg/d) was 0. Michael G. MPH Background Epidemiological studies suggested that consumption of fruit and vegetables may protect against stroke. Edith J. Daan Kromhout.12 to 0.84). PhD. PhD. including antioxidant vitamins. Conclusions The habitual intake of flavonoids and their major source (tea) may protect against stroke. L. PhD. and stroke incidence was assessed by Cox proportional hazards regression analysis. M.33). Hertog.7 cups or more of tea vs less than 2. Methods A cohort of 552 men aged 50 to 69 years was examined in 1970 and followed up for 15 years. and consumption of fish and alcohol. Dietary flavonoids (mainly quercetin) were inversely associated with stroke incidence after adjustment for potential confounders. and 1970. 1996.54. MD. Feskens.
Platelet aggregation is a precipitating event in cardiovascular disease. Vita. followed by 900 mL of tea or water daily for 4 weeks in a crossover design. but the mechanisms of benefit remain undefined. and neither relation was altered by acute or chronic tea consumption. Jr ABSTRACT Epidemiological studies suggest that tea consumption is associated with a decreased risk of cardiovascular events.Stephen J. Plasma flavonoids increased with acute and chronic tea consumption. indicating adequate absorption of tea flavonoids. Monika Holbrook. and tea contains antioxidant flavonoids that are known to decrease platelet aggregation in vitro. In conclusion. These findings suggest that an effect of tea flavonoids on platelet aggregation is unlikely to be the explanation for the reduction in risk of cardiovascular events noted in epidemiological studies. Ex vivo platelet aggregation in platelet-rich plasma was assessed in response to ADP and thrombin receptor–activating peptide at baseline and 2 hours and 4 weeks after beverage consumption. Peter L. John F. Joseph A. these results demonstrate that acute and chronic black tea consumption does not affect ex vivo platelet aggregation in patients with coronary artery disease. To test the effect of tea consumption on platelet aggregation. we randomized 49 patients with coronary artery disease to either 450 mL of black tea or water consumed initially.
A Review of Potential Health Benefits of Flavonoids
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. We observed dose-dependent platelet aggregation in response to each agonist. Swerdloff. Duffy. Keaney.
Plants and spices containing flavonoids have historically been used in traditional eastern medicine. viruses. Research in the field of flavonoids has increased since the discovery of the French paradox i. inflammation. ulcers. Brief description about the disease causing effect of free radicals is given and ways by which flavonoids neutralize free radicals has also been mentioned.
Flavonoids Affect Actin Functions in Cytoplasm and Nucleus
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. osteoporosis.e. diarrhea and arthritis. The major actions of flavonoids are those against cardiovascular diseases. Patel
Flavonoids occur naturally in fruit. and beverages such as tea and wine and over 4000 structurally unique flavonoids have been identified in plant sources. vegetables.Jay M. the low cardiovascular mortality rate observed in Mediterranean populations in association with red wine consumption and a high saturated fat intake. The aim of this review is to obtain a further understanding on the reported beneficial health effects of these substances and discuss the action of flavonoids as antioxidants.
Karim Fahmy and Herwig O. similar Kd values in the 20μM range were observed for six flavonoids encompassing members of the flavonol. Irrespective of differences in the hydroxyl pattern. rather than H-bond-mediated. Docking studies provide models of flavonoid binding to the known small moleculebinding sites in actin.Markus Böhl. Infrared spectroscopic evidence reveals flavonoid-specific conformational changes in actin which may mediate the different biological effects. the binding affinities of quercetin and structurally related flavonoids were determined by flavonoid-dependent quenching of tryptophan fluorescence from actin. The experimental and theoretical data consistently indicate the importance of hydrophobic. Among these.) Leaves by Macroscopous Adsorption
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. Depending on the rigidity of the flavonoid structures. the flavonoids exert distinct and partially opposing biological effects: although flavonols inhibit actin functions. Frank Pfennig. Simon Tietze.
Preparative Isolation of Flavonoids from Mulberry (Morus Alba L. Joannis Apostolakis. the mostly hydrophobic tetramethylrhodaminebinding site is a prime candidate for flavonoid binding and rationalizes the high efficiency of quenching of the two closely located fluorescent tryptophans. Sineej Madathil. flavanone. The potential biological relevance of the flavonoid/actin interaction in the cytoplasm and the nucleus was addressed using an actin polymerization and a transcription assay. the structurally related flavane epigallocatechin promotes actin activity in both test systems. isoflavone. Andrea Sokoll. different functionally relevant conformational changes are evoked through an induced fit. In contrast to the similar binding affinities. respectively. actin-flavonoid interactions. and flavane group. Gutzeit
Based on the identification of actin as a target protein for the flavonol quercetin.
and their recoveries were above 80%.DONGDONG JIA. The devised method of isolation of the flavonoids from mulberry leaves may be used to develop a new process for medicinal purpose. and the macroporous resin adsorption technology was further employed to purify the flavonoids. R. In this study. Rahmani and A.4% under the optimum conditions. Nikkhah Copyright Journal compilation © 2008 Blackwell Publishing Ltd
. Static and dynamic adsorption–desorption were tested to optimize the operation parameters. R. Ghorbani . H. SHUFEN LI and ZHIPENG GU
The flavonoids in mulberry leaves have good antioxidant activities.
Growth. The flavonoids of rutin and isoquercitrin in the extract were detected by high-performance liquid chromatography. The nonpolar resin labeled as H-103 was selected from eight kinds of macroporous resins as the adsorbent. G. with a recovery of 83. J. M. weaning performance and blood indicators of humoral immunity in Holstein calves fed supplemental flavonoids
S.3%. Yaghoubi . ultrasound-assisted extraction was used to obtain the crude flavonoids. The experimental results show that the purity of the total flavonoids can be 36.
the medium and high but not the low doses of flavonoids lowered serum IgG. At week 4. At week 8. 41. Albert Tenesa. Twenty Holstein calves [7 ± 2 days age. (ii) low (7. calves fed the high dose of flavonoids had higher BW than those fed no or low doses of flavonoids. (iii) medium (7. Susan M. Future studies are needed to further evaluate the premise that dietary forages or the main source of flavonoids are helpful for a less stressful weaning in the modern calf raising. The flavonoids were extracted from propolis.ABSTRACT
The primary objective was to test the hypothesis that flavonoids mediate immune response and affect calf performance. At week 5 of age. Mary Porteous.
Dietary Flavonoids and the Risk of Colorectal Cancer
Evropi Theodoratou. wither height and the severity of scours. At week 6. Malcolm Dunlop and Harry Campbell
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.3 × 10−5 g/kg BW). Rebecca Barnetson.6 × 10−3 g/kg BW) doses of flavonoids intake in a completely randomized design. both medium and low doses of flavonoids moderated serum IgG.4 ± 0. This response depended on calf age. Janet Kyle. BW was higher when calves fed the high compared to the low dose of flavonoids. The serum immunoglobulin G (IgG) concentrations remained lower at the first 3 weeks of the experiment when calves received the low but not the high doses of flavonoids. After weaning. Farrington. calves fed high and medium flavonoids doses had lower blood immunoglobulin M (IgM) than control calves. Results suggest that flavonoids affect the humoral immune response and can improve growth in young calves.3 × 10−4 g/kg BW). Calves received the treatments as a tablet until weaning or a daily intake of 680 g starter. calves received no supplemental flavonoids and monitored until 120 days of age. Treatments did not affect body length.7 kg body weight (BW)] were randomly assigned to four treatments of (i) no. At week 6. and (iv) high (3. Roseanne Cetnarskyj.
This was the first of several a priori hypotheses to be tested in this large study and showed strong and linear inverse associations of flavonoids with colorectal cancer risk. self-administered food frequency questionnaire. 32% for quercetin (OR. but no interaction beyond a multiplicative effect was present. a summary of the putative biological actions of flavonoids. Klaske van Norren and Paul AM van Leeuwen
The aim of this review.22). Ptrend = 0. 0.456 population-based controls matched on age. Sex-specific or cancer-type differences were not observed.68. 0. Recent expansions of dietary databases to include flavonoid data now make such studies feasible. 32% for catechin (OR. Flavonoids occur naturally in fruit. smoking status. were obtained from a validated. 0. Association between the six main classes of flavonoids and the risk of colorectal cancer was examined using data from a national prospective case-control study in Scotland. 0.In vitro and in vivo laboratory data point to chemoprotective effects of flavonoids on colorectal cancer. Ptrend = 0. The significant dose-dependent reductions in colorectal cancer risk that were associated with increased consumption of flavonols.26). vegetables. and phytoestrogens (Ptrend = 0. However. including flavonoid data.456 incident cases and 1. Danny EC van Hoorn. Risk of colorectal cancer was estimated using conditional logistic regression models in the whole sample and stratified by sex. No risk reductions were associated with intake of flavones (Ptrend = 0. Ptrend < 0. and residence area. quercetin.73. including 1. Els van Nood. was to obtain a further understanding of the reported beneficial health effects of these substances.0005).16(4):684–93)
Flavonoids: a review of probable mechanisms of action and potential applications
Robert J Nijveldt. After energy adjustment.031). reductions in colorectal cancer risk associated with the highest quartiles of intake (versus the lowest quartile) were 27% for flavonols [odds ratio (OR). 26% for epicatechin (OR. and cancer site and adjusted for established and putative risk factors. Ptrend = 0. Ptrend = 0.68. (Cancer Epidemiol Biomarkers Prev 2007.012].64). Petra G Boelens. flavonones (Ptrend = 0. Dietary. and 22% for procyanidins (OR. there has been limited epidemiologic research on the dietary intake of flavonoids and risk of colorectal cancer. and beverages such as tea
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. 0. The risk reductions were greater among nonsmokers.78.001).019). sex. and epicatechin remained robust after controlling for overall fruit and vegetable consumption or for other flavonoid intake. catechin.74.
the probablemechanisms by which they act. and the potential clinicalapplications of these fascinating natural substances American Journal of Clinical Nutrition. Jr Background: Dietary flavonoids may have beneficial cardiovascular effects in human populations.We review the different groups of known flavonoids. Leila M Barraj. the low cardiovascular mortality rate observed inMediterranean populations in association with red wine consumptionand a high saturated fat intake. No. Vol.
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. Jennifer A Nettleton and David R Jacobs. 4. but epidemiologic study results have not been conclusive.ie. Carolyn G Scrafford. Lisa Harnack.and wine. 74. 418-425. ChingPing Hong. Several other potentialbeneficial properties of flavonoids have since been ascertained. October 2001 © 2001 American Society for Clinical Nutrition
Flavonoid intake and cardiovascular disease mortality: a prospective study in postmenopausal women
Pamela J Mink. Research in the field of flavonoids has increased since the discovery of the French paradox.
Intakes of total flavonoids and 7 subclasses were categorized into quintiles. 85. 0.99). between flavanones and CHD [RR for highest quintile versus lowest: 0.90 (0. No association was found between flavonoid intake and stroke mortality.82.Objective: We used flavonoid food composition data from 3 recently available US Department of Agriculture databases to improve estimates of dietary flavonoid intake and to evaluate the association between flavonoid intake and cardiovascular disease (CVD) mortality. Vol. Markku Heliövaara.94)].
. associated with stroke and CVD). and 0. Harri Rissanen. anthocyanidins. Individual flavonoid-rich foods associated with significant mortality reduction included bran (added to foods. March 2007 © 2007 American Society for Nutrition
Flavonoid intake and risk of chronic diseases
Paul Knekt. Ritva Järvinen. and food sources were grouped into frequency categories. Timo Hakulinen and Arpo Aromaa ABSTRACT Background: Flavonoids are effective antioxidants and may protect against several chronic diseases. CVD. and total mortality [RR (95% CI) for any versus no intake: 0. and total mortality after 16 y of follow-up. 0. grapefruit (associated with CHD). and certain foods rich in flavonoids were associated with reduced risk of death due to CHD. American Journal of Clinical Nutrition. 0. Antti Reunanen.86.95)]. Jorma Kumpulainen. significant inverse associations were observed between anthocyanidins and CHD. No.78. strawberries (associated with CVD). 3. and all causes. CVD.91 (0. 0.88 (0. stroke. 895-909.96)].78 (0. 0. coronary heart disease (CHD). and chocolate (associated with CVD). 0. and between flavones and total mortality [RR for highest quintile versus lowest: 0.99). Proportional hazards rate ratios (RR) were computed for CVD. Design: Study participants were 34 489 postmenopausal women in the Iowa Women's Health Study who were free of CVD and had complete food-frequency questionnaire information at baseline.88 (0. Results: After multivariate adjustment.83.65. apples or pears or both and red wine (associated with CHD and CVD). Conclusion: Dietary intakes of flavanones.
Conclusion: The risk of some chronic diseases may be lower at higher dietary flavonoid intakes.76.22. Results: Persons with higher quercetin intakes had lower mortality from ischemic heart disease. Vol.06).62. The incident cases of the diseases considered were identified from different national public health registers. A trend toward a reduction in risk of type 2 diabetes was associated with higher quercetin (0. 560-568. P = 0.86. P = 0.07) intakes.88.001). The incidence of cerebrovascular disease was lower at higher kaempferol (0.80. Simin Liu and Julie E Buring ABSTRACT Background: Despite emerging evidence of the role of flavonoids in cardiovascular disease (CVD) prevention.63. Men with higher quercetin intakes had a lower lung cancer incidence (0.07) and myricetin (0. 0.43. Design: The total dietary intakes of 10 054 men and women during the year preceding the baseline examination were determined with a dietary history method.008) intakes. The relative risk (RR) between the highest and lowest quartiles was 0. P = 0. 0. 0. P = 0. 0. the association remains unclear.03) intakes.01.98.69.46. P = 0. 0. P = 0. September 2002 © 2002 American Society for Clinical Nutrition
Flavonoid intake and the risk of cardiovascular disease in women
Howard D Sesso. 0.00.64. naringenin (0.25. 0.56. J Michael Gaziano. P = 0.81.72. 3. No. and hesperetin (0.99. 0.79. 1.003). 0.005). 0.02). 76. Asthma incidence was lower at higher quercetin (0.99: P for trend = 0. 1. P = 0.Objective: The association between flavonoid intake and risk of several chronic diseases was studied. Flavonoid intakes were estimated. 0. 0.06). mainly on the basis of the flavonoid concentrations in Finnish foods.70. and men with higher myricetin intakes had a lower prostate cancer risk (0. 0. American Journal of Clinical Nutrition. P = 0.50. 0.79 (95% CI: 0.64.86. 0.56.79.42. 0.64.
. naringenin (0.94. 1. P = 0. and hesperetin (0.002). 0.02. 0.64.
5 mg/d. Vol. Broccoli and apple consumption were associated with nonsignificant reductions in CVD risk: 25–30% and 13–22%.80. and tea with CVD were not mediated by flavonoids and warrant further study. June 2003 © 2003 American Society for Clinical Nutrition
Comparison of the antioxidant effects of Concord grape juice flavonoids -tocopherol on markers of oxidative stress in healthy adults
Dawn J O’Byrne. revascularization.2%). apples. For both CVD and important vascular events. respectively). No. total flavonoids and selected flavonols and flavones were categorized into quintiles.9 y. respectively. Conclusions: Flavonoid intake was not strongly associated with a reduced risk of CVD.Objective: We examined whether flavonoids and selected flavonols and flavones or their food sources are associated with CVD risk. stroke. and CVD death. A small proportion of women (n = 1185) consuming ≥4 cups (946 mL) tea/d had a reduction in the risk of important vascular events but with a nonsignificant linear trend (P = 0. including myocardial infarction. and food sources were categorized into 4 groups. Scott M Grundy and Ishwarlal Jialal ABSTRACT
. 77. American Journal of Clinical Nutrition. 6. The nonsignificant inverse associations for broccoli. no significant linear trend was observed across quintiles of flavonoid intake (P = 0.6 ± 18. primarily as quercetin (70. Results: The mean flavonoid intake was 24. Design: Women (n = 38 445) free of CVD and cancer participated in a prospective study with a mean follow-up of 6. excluding revascularizations) and CVD (729 events).07). Sridevi Devaraj. On the basis of a food-frequency questionnaire.63 and 0. 1400-1408. Relative risks were computed for important vascular events (519 events. No individual flavonol or flavone was associated with CVD.
01). Protein carbonyl concentrations in native plasma decreased 20% after CGJ supplementation. American Journal of Clinical Nutrition. Conclusions: In healthy adults. which was a significantly different response than that after -tocopherol supplementation (P < 0. the efficacies of flavonoids and -tocopherol in vivo have not been compared. Objective: We compared the in vivo antioxidant efficacy of CGJ with that of tocopherol in healthy adults. 76. Andrea Celestini. Serum oxygen radical absorbance capacity. Pier Paolo Gazzaniga and Francesco Violi ABSTRACT
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.05). plasma -tocopherol increased 92% in subjects who received -tocopherol (P < 0.001) and LDL lag time (P < 0. Results: After supplementation.-tocopherol/d (n = 17) or 10 mL CGJ · kg-1 · d-1 (n = 15) for 2 wk. There was a significant change in plasma triacylglycerols in both groups. Both supplementation regimens significantly increased serum oxygen radical absorbance capacity (P < 0. 10 mL CGJ · kg-1 · d-1 increased serum antioxidant capacity and protected LDL against oxidation to an extent similar to that obtained with 400 IU -tocopherol/d but decreased native plasma protein oxidation significantly more than did -tocopherol. No. plasma total and conjugated phenols increased 17% (P < 0. Design: Subjects were randomly assigned to receive either 400 IU RRR. CGJ flavonoids are potent antioxidants that may protect against oxidative stress and reduce the risk of free radical damage and chronic diseases. respectively. urinary F2-isoprostanes.001) and significantly decreased the LDL oxidation rate (P < 0. Luisa Lenti. CGJ supplementation was associated with significantly higher triacylglycerols than was -tocopherol supplementation. December 2002 © 2002 American Society for Clinical Nutrition
The flavonoids quercetin and catechin synergistically inhibit platelet function by antagonizing the intracellular production of hydrogen peroxide
Pasquale Pignatelli. in subjects who received CGJ.01) and 22% (P < 0. 6.001). and resistance of LDL to ex vivo oxidation were measured before and after supplementation as markers of antioxidant status and oxidative stress. plasma protein carbonyls. with no significant difference in effectiveness. Fabio M Pulcinelli. 1367-1374. however. Vol. which have greater antioxidant efficacy in vitro than does -tocopherol.001). but the concentrations were within the normal range.Background: Concord grape juice (CGJ) is a rich source of flavonoids. Andrea Ghiselli.
but evidence is still conflicting. No. Objective: Because we showed previously that collagen-induced platelet aggregation is associated with a burst of hydrogen peroxide. Conclusions: These data indicate that flavonoids inhibit platelet function by blunting hydrogen peroxide production and.3.
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. in turn. significantly inhibited collagen-induced platelet aggregation and platelet adhesion to collagen. but the underlying mechanism has not yet been identified. Albert Hofman and Jacqueline CM Witteman ABSTRACT Background: Dietary flavonoids may protect against cardiovascular disease. Results: Catechin (50–100 µmol/L) and quercetin (10–20 µmol/L) inhibited collageninduced platelet aggregation and platelet adhesion to collagen. 5. neither of which had any effect on platelet function when used alone. calcium mobilization. Tea is the major source of flavonoids in Western populations. 72.Background: Epidemiologic studies have shown an inverse relation between moderate consumption of red wine and cardiovascular disease. quercetin and catechin. phospholipase C activation and suggest that the synergism among flavonoids could contribute to an understanding of the relation between the moderate consumption of red wine and the decreased risk of cardiovascular disease. 1150-1155. on collageninduced platelet aggregation and hydrogen peroxide and on platelet adhesion to collagen. and 1. Deirdre AM van der Kuip. Design: We tested the effect of 2 flavonoids.4-inositol triphosphate formation. the aim of this study was to investigate whether flavonoids synergize in inhibiting platelet function and interfere with platelet function by virtue of their antioxidant effect. American Journal of Clinical Nutrition. Such a combination strongly inhibited collageninduced hydrogen peroxide production. Lenore J Launer. Studies have shown that red wine and its component flavonoids inhibit in vivo platelet activation. Vol. November 2000 © 2000 American Society for Clinical Nutrition
Inverse association of tea and flavonoid intakes with incident myocardial infarction: the Rotterdam Study
Johanna M Geleijnse. The combination of 25 µmol catechin/L and 5 µmol quercetin/L. which in turn contributes to stimulating the phospholipase C pathway.
The inverse association with tea drinking was stronger for fatal events (0. The analysis included 4807 subjects with no history of myocardial infarction. 30 of which were fatal. Objective:We aimed to systematically review the effectiveness of different flavonoid subclasses and flavonoid-rich food sources on cardiovascular disease (CVD) and risk factors—ie. No.35. Design: A longitudinal analysis was performed with the use of data from the Rotterdam Study—a population-based study of men and women aged 55 y. Kathryn A Le Cornu. 0. The relative risk (RR) of incident myocardial infarction was lower in tea drinkers with a daily intake >375 mL (RR: 0. smoking status.Objective: The association of tea and flavonoid intake with incident myocardial infarction was examined in the general Dutch population. Wendy L Hall and Aedín Cassidy ABSTRACT Background:The beneficial effects of flavonoid consumption on cardiovascular risk are supported by mechanistic and epidemiologic evidence. 5. saturated fat. sex. 95% CI: 0. Paul A Kroon. a total of 146 first myocardial infarctions occurred. lipoproteins. 880-886. who were followed until 31 December 1997.98) in upper compared with lower tertiles of intake. Diet was assessed at baseline (1990–1993) with a validated semiquantitative food-frequency questionnaire. 1. blood pressure.
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. and flow-mediated dilatation (FMD).98) than in nontea drinkers. Results: During 5. 0. and daily intakes of alcohol.13. 0. body mass index. Ian Harvey.94) than for nonfatal events (0. Jonathan J Ryder. flavonoid-rich foods. with adjustment for age.37. vitamin E. 0.57. 75. Data were analyzed in a Cox regression model. and cardiovascular risk: a meta-analysis of randomized controlled trials
Lee Hooper. and total energy.09. The intake of dietary flavonoids (quercetin + kaempferol + myricetin) was significantly inversely associated only with fatal myocardial infarction (0. 0. fiber.68.33. pack-years of cigarette smoking. May 2002 © 2002 American Society for Clinical Nutrition
Flavonoids. education level.6 y of follow-up. American Journal of Clinical Nutrition. polyunsaturated fat. Eric B Rimm. 0.26). coffee.30. Vol. Jeffrey S Cohn.
12.34. and Cochrane databases.99%.62. 5.55. Results:One hundred thirty-three trials were included. Jeffrey B Blumberg. and be of long enough duration to allow assessment of clinically relevant endpoints. 2 studies) intake and reduced systolic (–5. July 2008 © 2008 American Society for Nutrition
Dietary intake of selected flavonols.03.83.86. and validity assessment. flavones. 4 studies).
. –1. data extraction. –9. Chocolate increased FMD after acute (3. examine dose-response effects.28. the effects of flavonoids from soy and cocoa have been the main focus of attention. American Journal of Clinical Nutrition. 4. –2. and meta-analysis. 88. Shumin M Zhang.52. For many of the other flavonoids. 1. Significant heterogeneity confirmed differential effects between flavonoid subclasses and foods. Future studies should focus on other commonly consumed subclasses (eg. anthocyanins and flavanones). –0.21. Acute black tea consumption increased systolic (5.19 mmol/L.30 mm Hg. –0. Conclusions:To date. there was insufficient evidence to draw conclusions about efficacy. No randomized controlled trial studied effects on CVD morbidity or mortality. 1. –5. No. 1. Objective: We prospectively investigated the association between the intake of selected flavonoids and flavonoid-rich foods and risk of cancers in the Women's Health Study.56 mm Hg. formal inclusion or exclusion. –0.Design:Methods included a structured search strategy on MEDLINE. 38-50.23 mmol/L. –0. However.10.86. –0. 6 studies) and chronic (1. –2. I-Min Lee. Vol. 9.12. epidemiologic studies on dietary flavonoids and cancer risk have yielded inconsistent results.88 mm Hg.220.127.116.11. 9 studies) and LDL cholesterol (–0. Green tea reduced LDL (–0. 39 studies). 2. 0. Soy protein isolate (but not other soy products or components) significantly reduced diastolic blood pressure (– 1. 4 studies) and diastolic (2. 95% CI: 2. 4 studies) blood pressure.69 mm Hg.77. and flavonoid-rich foods and risk of cancer in middleaged and older women
Lu Wang. EMBASE. 4 studies) blood pressure. 5 studies) and diastolic (–3.99 mm Hg. Julie E Buring and Howard D Sesso Abstarct Background: Flavonoids may protect against cancer development through several biological mechanisms.45%.
and 1.5 y of follow-up among 38. Objective: We aimed to evaluate the hypothesis that higher flavonoid intake is associated with lower NHL risk. Dietary flavonoids are polyphenolic compounds proposed to be anticarcinogenic. 0. Results: The multivariate RRs of total cancer across increasing quintiles of total quantified flavonoid intake were 1. 89.93.03 for lung cancer.00. 1. kaempferol. and 0.
American Journal of Clinical Nutrition. Conclusion: Our results do not support a major role of 5 common flavonols and flavones or selected flavonoid-rich foods in cancer prevention. No. Maryjean Schenk.94. broccoli. onion. Flavonoids are well-characterized antioxidants and metal chelators.408 women aged 45 y. Cox regression models were used to estimate the relative risk (RR) of total and site-specific cancer across increasing intakes of total and individual selected flavonoids and flavonoid-rich foods (tea. 1. March 2009 © 2009 American Society for Clinical Nutrition
Dietary flavonoid intake and non-Hodgkin lymphoma risk
Cara L Frankenfeld.72). There was also no significant association between intake of flavonoid-rich foods and the incidence of total and site-specific cancers.01 for colorectal cancer. Lindsay M Morton.97 (P for trend = 0. Wendy Cozen.
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.05). 905-912. Intake of individual flavonols (quercetin. 1.Design: A total of 3234 incident cancer cases were identified during 11. For site-specific cancers.03 for breast cancer.09 for ovarian cancer (all P > 0.26913 Vol.15 for endometrial cancer. and tofu). apple. James R Cerhan.00. The associations for the individual flavonoid intakes were similar to those for the total intake. and certain flavonoids exhibit antiproliferative and antiestrogenic effects. 1.3945/ajcn. the multivariate RRs in the highest quintile of total quantified flavonoid intake compared with the lowest quintile were 1. 3. Patricia Hartge and Mary H Ward ABSTRACT Background: The role of dietary factors in non-Hodgkin lymphoma (NHL) risk is not yet well understood. Scott Davis. and myricetin) and flavones (apigenin and luteolin) was assessed from food-frequency questionnaires.2008. 0. doi:10.
tocopherols. However. sex. flavonoid intake was estimated from participant responses to a 117-item food-frequency questionnaire (n = 466 cases and 390 controls). and sex. Epidemiology. anthocyanidins. 1439-1445. 87. even after extensive flavonoid intake. may be associated with lower NHL risk. and energy intake. Controls without history of NHL were selected by random-digit dialing or from Medicare files and frequencymatched to cases by age. and proanthocyanidins were each significantly associated with decreased NHL risk. NHL risk in relation to flavonoid intake in quartiles was evaluated after adjustment for age. Results: Higher total flavonoid intake was significantly associated with lower risk of NHL (P for trend < 0.01): a 47% lower risk in the highest quartile of intake than in the lowest (95% CI: 31%. and End Results cancer registries. Similar patterns of risk were observed for the major NHL subtypes—diffuse large B-cell lymphoma (n = 167) and follicular lymphoma (n = 146). Using 3 recently developed US Department of Agriculture nutrient-specific databases. registry. center. we identified incident NHL cases aged 20–74 y from 4 US Surveillance. education. race.
American Journal of Clinical Nutrition. 5. 73%). epicatechins. No. especially flavonoids. it remains unclear whether this protective effect is attributable to the phenols or to other agents in the diet. and other phenols: direct or indirect effects? Antioxidant or not?
Barry Halliwell. Joseph Rafter and Andrew Jenner
Foods and beverages rich in phenolic compounds. tocotrienols. Vol. This may be because maximal plasma concentrations.Design: During 1998–2000. Alleged health-promoting effects of flavonoids are usually attributed to their powerful antioxidant activities. may be low (insufficient to exert significant systemic
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. Conclusion: A higher intake of flavonoids. NHL family history. May 2008 © 2008 American Society for Nutrition
Health promotion by flavonoids. have often been associated with decreased risk of developing several diseases. Higher intakes of flavonols. but evidence for in vivo antioxidant effects of flavonoids is confusing and equivocal. dietary components with several putative anticarcinogenic activities.
Barry Halliwell. and oxygen species. and perhaps inhibition of cyclooxygenases and lipoxygenases. Reports of substantial increases in plasma total antioxidant activity after flavonoid intake must be interpreted with caution. Onions and black tea are foods rich in flavonoids. which is a potent in vitro inhibitor of membrane lipid peroxidation and LDL oxidation. Tom AB Sanders and Helen Wiseman Abstact Background: Oxidative damage to lipids in vivo may be involved in the development of atherosclerosis and cancer. Objective: Our objective was to investigate the effects of consuming a high-flavonoid (HF) diet enriched with onions and black tea on indexes of oxidative damage in vivo compared with a low-flavonoid (LF) diet. findings may be attributable to changes in urate concentrations. scavenging of reactive nitrogen. Ian S Young.
. 268S-276S. We argue that tocopherols and tocotrienols may also exert direct beneficial effects in the gastrointestinal tract and that their return to the gastrointestinal tract by the liver through the bile may be physiologically advantageous. 1. Our measurements of flavonoids and other phenols in human fecal water are consistent with this concept. However. Anthony I Mallet. Vol. American Journal of Clinical Nutrition. predominantly the flavonoid quercetin. These effects could include binding of prooxidant iron. 81. phenols might exert direct effects within the gastrointestinal tract. Gareth T McAnlis. chlorine. January 2005 © 2005 American Society for Clinical Nutrition
Consumption of flavonoids in onions and black tea: lack of effect on F2-isoprostanes and autoantibodies to oxidized LDL in healthy humans
James D O'Reilly. No. because of the high concentrations present.antioxidant effects) and because flavonoid metabolites tend to have decreased antioxidant activity.
quercetin (22%). quercetin-3-glucoside.generated DNA damage from hydrogen peroxide (100 micromol/L) in human lymphocytes were examined by using the single-cell gel electrophoresis assay (comet assay). No. 6. Vol. 73. kaempferol (32%). At a concentration of 279 micromol/L. however. quercetin. plasma concentrations of the F2-isoprostane 8-epi-prostaglandin F2 were slightly higher after the HF treatment phase than after the LF treatment [0.3-glucoside (62%). In the men. plasma F2-isoprostane concentrations. American Journal of Clinical Nutrition. quercitrin (quercetin-3-Lrhamnoside) (45%). 93.2 nmol/L. June 2001 © 2001 American Society for Clinical Nutrition
Effects of flavonoids and vitamin C on oxidative DNA damage to human lymphocytes
M Noroozi.6. The antioxidant effects of pretreatment with flavonoids and vitamin C. The ranking was similar
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. 23. 1040-1044. The protective effect of vitamin C against DNA damage at this concentration was significantly less than that of all the flavonoids except apigenin. and 279. apigenin (59%). Pretreatment with all flavonoids and vitamin C produced dose-dependent reductions in oxidative DNA damage. In all subjects.029 nmol/L (111 ± 10. WJ Angerson and ME Lean This study assessed the antioxidant potencies of several widespread dietary flavonoids across a range of concentrations and compared with vitamin C as a positive control. and MDA-LDL autoantibody titer between the HF and LF dietary treatments.8 ng/L).Design: Thirty-two healthy humans were studied in a randomized crossover design. P = 0.022 nmol/L (92 ± 7. and vitamin C (78%). myricetin (10%).6 ± 37.2. Indexes of oxidative damage used were plasma F2-isoprostanes (a biomarker of lipid peroxidation in vivo) and the titer of antibodies to malondialdehyde (MDA)-modified LDL. and rutin.041].4 nmol/L compared with less than the limit of detection of 66. plasma quercetin concentrations were significantly higher after the HF treatment phase than after the LF treatment: 221. Conclusion: Flavonoid consumption in onions and tea had no significant effect on plasma F2-isoprostane concentrations and MDA-LDL autoantibody titer in this study and thus does not seem to inhibit lipid peroxidation in humans.26 ± 0. rutin (quercetin-3beta-D-rutinoside) (82%). at standardized concentrations (7. on oxygen radical.4 micromol/L).31 ± 0.4 ng/L) compared with 0. they were ranked in decreasing order of potency as follows: luteolin (9% of damage from unopposed hydrogen peroxide). Results: There were no significant differences in the intake of macronutrients or assessed micronutrients.
001). NO-dependent. Copyright © 1998 by The American Society for Clinical Nutrition. 1210-1218. This action may confer antileukotriene action in vivo. we assessed whether cocoa polyphenols inhibited human 5-lipoxygenase. These data suggest that the free flavonoids are more protective than the conjugated flavonoids (eg. Vol 67. both in combination: 62%). The protective effect of quercetin and vitamin C at a concentration of 23. Because intake of flavonoid-rich chocolate by human subjects was reported to decrease the plasma concentrations of proinflammatory cysteinyl leukotrienes.2 micromol/L was found to be additive (quercetin: 71% of maximal DNA damage from unopposed hydrogen peroxide. Data are also consistent with the hypothesis that antioxidant activity of free flavonoids is related to the number and position of hydroxyl groups. quercetin compared with its conjugate quercetin-3-glucoside. and it was shown that ingestion of the high-flavanol coca drink but not the low-flavanol cocoa drink
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. P < 0. Christian Heiss and Malte Kelm
Cocoa products are sources of flavan-3-ols.with estimated ED50 (concentration to produce 50% protection) values. Inc
Cocoa polyphenols and inflammatory mediators
Helmut Sies. In a double-blind crossover study. This review provides a survey of our research on the effects of cocoa polyphenols on leukotriene and nitric oxide (NO) metabolism and on myeloperoxidase-induced modification of LDL. vitamin C: 83%. 20 individuals at risk for cardiovascular diseases received cocoa beverages with high or low contents of flavan-3-ols. American Journal of Clinical Nutrition. flow-mediated dilation of the brachial artery and concentrations of nitroso compounds in plasma were measured. (–)Epicatechin and other cocoa flavan-3-ols proved to be inhibitory at the enzyme level. Tankred Schewe. the key enzyme of leukotriene synthesis. which have attracted interest regarding cardiovascular health.
were thus attenuated. Exogenous indole-3-acetic acid (IAA) also elevated flavonoid accumulation. Flavonoid accumulation was higher in gravity-stimulated root tips as compared with vertical controls. and one of the mediators is the proinflammatory proatherogenic enzyme myeloperoxidase. Buer and Gloria K. 81. 1. Muday
We examined whether flavonoids act as endogenous auxin transport regulators during gravity vector and light intensity changes in Arabidopsis thaliana roots. The tt4(2YY6) roots had delayed gravitropism that was chemically complemented with a flavonoid intermediate. with maximum differences coinciding with the timing of gravitropic bending. but flavonoid accumulation was absent in tt4(2YY6) roots. and in epidermal and cortical cells. the site of differential growth. Flavonoid accumulation was found in wild-type columella cells. suggesting that flavonoid changes in response to gravity might be partly as a result of changing IAA distribution.significantly increased plasma concentrations of nitroso compounds and flow-mediated dilation of the brachial artery. consistent with the absence of a negative auxin transport regulator. Flavonoid deficient transparent testa4 [tt4(2YY6)] seedlings had elevated root basipetal auxin transport compared with the wild type. an NO metabolite. and was located in epidermal cells. Acropetal
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. No. such as nitrite and peroxynitrite.
American Journal of Clinical Nutrition. January 2005 © 2005 American Society for Clinical Nutrition
The transparent testa4 Mutation Prevents Flavonoid Synthesis and Alters Auxin Transport and the Response of Arabidopsis Roots to Gravity and Light
Charles S. 304S-312S. ingested flavonoids may reverse endothelial dysfunction through enhancement of NO bioactivity. Therefore. Oxidative modification of LDL appears to be crucial for atherogenesis. the site of gravity perception. Vol. Micromolar concentrations of (–)-epicatechin or other flavonoids were found to suppress lipid peroxidation in LDL induced by myeloperoxidase in the presence of physiologically relevant concentrations of nitrite. Adverse effects of NO metabolites.
1.09). This effect has been attributed to their high flavonoid content. J. the present study examined whether dietary intake of catechins. Asthma was defined by positive responses to a standard screening questionnaire in 1996 and information about usual diet was obtained by a food frequency questionnaire in 1997. as were differences in root acropetal transport in tt4(2YY6). asthma severity and chronic sputum production. L. flavonols and total catechins. In a population-based. C. Thompson and S. respectively) nor was it associated with asthma severity. dietary intake of these three flavonoid subclasses was not significantly associated with asthma. These results are consistent with light.94 (0. 0.86–1. Sterne.IAA transport was also elevated in roots of tt4(2YY6). R. After controlling for potential confounders. A. O. Shaheen
Epidemiological studies have suggested that a high consumption of apples may protect against asthma and chronic obstructive pulmonary disease.471 adults aged 16–50 yrs in London (UK).98 (0.00 (0. W. Arts. C. I.02).88 –1. but few studies have investigated the relationship between flavonoid intake and obstructive lung disease directly. flavonols and flavones was negatively associated with asthma. case-control study of 1. (odds ratio per quintile (95% confidence interval) = 0.
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.92–1.and gravity-induced flavonoid stimulation that alters auxin transport in roots and dependent physiological processes.08) for flavones. or chronic sputum production. including gravitropic bending and root development. The Plant Cell 16:1191-1205 (2004) © 2004 American Society of Plant Biologists
Dietary intake of flavonoids and asthma in adults
V. Garcia. Flavonoid synthesis was repressed in the dark.
Folts. Acute cardiac events are also associated with decreased platelet-derived nitric oxide (NO) release. Liqing Li. respectively). Methods and Results—Incubation of platelets with dilute PGJ led to inhibition of aggregation.5±5.05. It is possible that other flavonoids or polyphenols present in apples may explain the protective effect of apples on obstructive lung disease. To confirm the in vivo relevance of these findings. In this study. Eur Respir J 2005. and superoxide release decreased from 29.9 µmol/L. PhD. MD.009). III. and decreased superoxide production.5 pmol/108 platelets.0 to 19. Deak.05.6±0. PhD. and both red wine and purple grape juice (PGJ) contain flavonoids with antioxidant and antiplatelet properties believed to be protective against cardiovascular events. MD. Mark D.1183/09031936.2±3.6±0. 20 healthy subjects consumed 7 mL · kg-1 · d-1 of PGJ for 14 days. -Tocopherol levels increased significantly after PGJ consumption (from 15. the effects of PGJ and PGJ-derived flavonoids on platelet function and platelet NO production were determined. 26:449-452 Copyright ©ERS Journals Ltd 2005 doi: 10.0±1.007 and P<0. Perlman. Iafrati.5±1.2 to 6. Vadim Ivanov. Jacob A.In conclusion. Leslie R. no evidence was found for a protective effect of three major subclasses of dietary flavonoids on asthma. platelet-derived NO production increased from 3. BS. Freedman.7 to 17. P<0. Platelet aggregation was inhibited after PGJ supplementation. John D. MS. PhD
Background—Moderate red wine consumption is inversely associated with coronary ischemia. enhanced release of platelet-derived NO. Crawford Parker.00142104
Select Flavonoids and Whole Juice From Purple Grapes Inhibit Platelet Function and Enhance Nitric Oxide Release
Jane E. Balz Frei. and
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.1 arbitrary units (P<0. MD.
and some have been shown to possess antiparasitic activity. Conclusions—Both in vitro incubation and oral supplementation with PGJ decrease platelet aggregation.103:2792.0% (P<0. eight showed antiplasmodial activity against the 3D7 strain (with IC50 values between 11 and 66 μM). increase platelet-derived NO release. Inc.) © 2001 American Heart Association.
Common dietary flavonoids inhibit the growth of the intraerythrocytic malaria parasite
Adele M Lehane and Kevin J Saliba
BMC Research Notes 2008. platelet aggregation. independent of alcohol consumption. respectively. Of the eleven flavonoids tested. and did not affect parasite susceptibility to the antimalarial drugs chloroquine or artemisinin.1186/1756-0500-1-26 Published:18 June 2008
Flavonoids are abundant plant phenolic compounds.A chloroquine-sensitive (3D7) and a chloroquine-resistant (7G8) strain of P. with IC50 values of 11 ± 1 μM and 12 ± 1 μM for 3D7 and 7G8. and decrease superoxide production. 2001. Here we investigate the effects of a range of common dietary flavonoids on the growth of two strains of the human malaria parasite Plasmodium falciparum.the plasma protein–independent antioxidant activity increased by 50. 1:26doi:10. Last. Combining low concentrations of flavonoids was found to produce an apparent additive antiplasmodial effect. and all showed activity against the 7G8 strain (with IC50 values between 12 and 76 μM). (Circulation. and NO release. falciparum were tested for in vitro susceptibility to a range of individual dietary flavonoids and flavonoid combinations. More than 6000 have been identified to date.05). in cardiovascular disease. These findings may be a result of antioxidant-sparing and/or direct effects of select flavonoids found in PGJ. The suppression of platelet-mediated thrombosis represents a potential mechanism for the beneficial effects of purple grape products. Certain common dietary flavonoids inhibit the intraerythrocytic
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. Luteolin was found to prevent the progression of parasite growth beyond the young trophozoite stage. incubation of platelets with select flavonoid fractions isolated from PGJ consistently attenuated superoxide levels but had variable effects on whole-blood aggregation. The most active compound against both strains was luteolin. Parasite susceptibility was measured in 96-well plates over 96 h using a previously described [3H]hypoxanthine incorporation assay.
VvF3'5'H1. and antioxidant capacity. which altered flower color and flavonoid composition as expected. the expression of VvF3'5'H1 and VvCytoB5 in white grapes during ripening was extremely low. Hydroxylation of the B-ring of flavonoids is catalyzed by flavonoid 3'-hydroxylase (F3'H) and flavonoid 3'.and 3'.5'-hydroxylated anthocyanins. We report the identification of genes encoding F3'H. Debra McDavid and Simon P. Robinson ABSTRACT Flavonoids are important secondary metabolites in many fruits. and VvCytoB5 in grapes is coordinated with
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.growth of the 3D7 and 7G8 strains of P.
Identification of the Flavonoid Hydroxylases from Grapevine and Their Regulation during Fruit Development
Jochen Bogs. Flavonoid combinations warrant further investigation as antiplasmodial agents. In contrast to red grapes. when proanthocyanidins (PAs) are synthesized. and may also require cytochrome b5. and a putative cytochrome b5 from grapevine (Vitis vinifera L. Our results show that temporal and tissuespecific expression of VvF3'H. VvF3'H and VvCytoB5 were expressed in seeds but not VvF3'5'H1. when 3'-hydroxylated flavonols are made. VvF3'H was expressed in grapes before flowering. Ali Ebadi. and all three genes were expressed after flowering.5'hydroxylase (F3'5'H). Functionality of the genes VvF3'H and VvF3'5'H1 was demonstrated by ectopic expression in petunia (Petunia hybrida). where VvF3'H. VvCytoB5 expression was correlated with expression of both VvF3'H and VvF3'5'H1 in the different grape tissues. suggesting a difference in transcriptional regulation. VvF3'5'H1. and VvCytoB5 were highly expressed during ripening. consistent with the accumulation of 3'-hydroxylated PAs in this tissue. falciparum. cv Shiraz) and their transcriptional regulation in fruit. stability. In berry skin. expression of all three genes was low at the onset of ripening (véraison) but increased after véraison concomitant with the accumulation of 3'. and their hydroxylation pattern determines their color. F3'5'H.
from anticancer and antibacterial activities through to inhibition of bone resorption. Understanding the regulation of flavonoid hydroxylases could be used to modify flavonoid composition of fruits. the interactions between flavonoids and lipid bilayers as well as biological membranes and their components are reviewed.17457254.00238. with special emphasis on the structure-activity relationships and mechanisms underlying the biological activity of flavonoids.2006. In the present paper.html
. doi:10.the accumulation of the respective hydroxylated flavonols and PAs.nature.
Plant Physiology 140:279-291 (2006) © 2006 American Society of Plant Biologists
Flavonoid-membrane interactions: possible consequences for biological effects of some polyphenolic compounds
Andrzej B Hendrich
Flavonoids are found ubiquitously in higher plants and constitute an important component of the majority of peoples' daily diets. as well as anthocyanins. The biological activities of flavonoids cover a very broad spectrum. 27–40.1111/j.x
Acta Pharmacologica Sinica (2006) 27.com/aps/journal/v27/n1/abs/aps20062a.
Antonio Vella. Methods: K2-EDTA derived leukocyte buffy coats enriched in basophil granulocytes were treated with different concentrations of quercetin and triggered with anti-IgE. the calcium ionophore A23187 and the phorbol ester PMA in different experimental conditions. exerts a modulatory action at nanomolar concentrations on human basophils. Quercetin. Anita Conforti. Basophils were captured in a flow cytometry analysis as CD123bright/HLADRnon expressing cells and fluorescence values of the activation markers CD63-FITC or
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.Bimodal action of the flavonoid quercetin on basophil function: an investigation of the putative biochemical targets
Salvatore Chirumbolo. a large group of polyphenolic metabolites derived from plants have received a great deal of attention over the last several decades for their properties in inflammation and allergy. the most abundant of plant flavonoids. Riccardo Ortolani and Paolo Bellavit
Flavonoids. As this mechanism needs to be elucidated. fMLP. Marta Marzotto. in this study we focused the possible signal transduction pathways which may be affected by this compound.
CD203c-PE were used to produce dose response curves. 8:13doi:10. Clinical and Molecular Allergy 2010. thus suggesting a role for PI3K involvement in the priming mechanism. The specific phosphoinositide-3 kinase (PI3K) inhibitor wortmannin exhibited the same behavior of quercetin in anti-IgE and fMLP activation. Nanomolar concentrations of quercetin were able to prime both markers expression and histamine release in the fMLP activation model while no effect of quercetin was observed when basophils were activated with PMA.com/content/8/1/13/abstract
. These results rule out a possible role of protein kinase C in the complex response of basophil to quercetin. while indirectly suggest PI3K as the major intracellular target of this compound also in human basophils.1186/1476-7961-8-13
Published:17 September 2010
http://www. Quercetin inhibited the expression of CD63 and CD203c and the histamine release in basophils activated with anti-IgE or with the ionophore: the IC50 in the antiIgE model was higher than in the ionophore model and the effects were more pronounced for CD63 than for CD203c.clinicalmolecularallergy. The same population was assayed for histamine release.