Flavonols and cardiovascular disease

Perez-Vizcaino, Francisco; Duarte, Juan

doi:10.1016/j.mam.2010.09.002

Cited by 393Phytochemicals and Antioxidant ActivitiesFlavonoids in Medical ResearchNutritional Studies and Diet

Flavonols and cardiovascular disease

Perez-Vizcaino, Francisco, Duarte, Juan·2010·Molecular Aspects of Medicine

DOI 10.1016/j.mam.2010.09.002

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Abstract

Flavonols, and specially quercetin, are widely distributed in plants and are present in considerable amounts in fruits and vegetables. In addition to their anti-oxidant effect, flavonols interfere with a large number of biochemical signaling pathways and, therefore, physiological and pathological processes. There is solid evidence that, in vitro, quercetin and related flavonols exert endothelium-independent vasodilator effects, protective effect on nitric oxide and endothelial function under conditions of oxidative stress, platelet antiaggregant effects, inhibition of LDL oxidation, reduction of adhesion molecules and other inflammatory markers and prevention of neuronal oxidative and inflammatory damage. The metabolites of quercetin show partial protective effects on endothelial function and LDL oxidation. Quercetin produces undisputed antihypertensive and antiatherogenic effects, prevents endothelial dysfunction and protects the myocardium from ischemic damage. It has no clear effects on serum lipid profile and on insulin resistance. Human intervention trials with isolated flavonols demonstrate an antihypertensive effect. The meta-analysis of epidemiological studies show an inverse association between flavonol (together with flavone) intake and coronary heart disease and stroke. Therefore, although there is no solid proof yet, a substantial body of evidence suggests that quercetin may prevent the most common forms of cardiovascular disease contributing to the protective effects afforded by fruits and vegetables.

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HN vegetables do not induce tolerance, as suggested by our 7 d study, the 10 d study by Sobko et al., and a 15 d study by Vanhatalo et al.
“The results of our 7 d study, the 10 d study described above (20) and a 15 d study by Vanhatalo et al. (34) suggest that HN vegetables do not induce tolerance, which is a potential advantage over the therapeutic use of organic nitrates (26) .”
From High-nitrate vegetable diet increases plasma nitrate and nitrite concentrations and reduces blood pressure in healthy women (2015) · cites this paper as [34]
Some observational studies evaluating total or selected dietary flavonoids observe lower risk of cardiometabolic events; no long-term clinical trials have been performed.
“Some observational studies evaluating total or selected dietary flavonoids observe lower risk of cardiometabolic events;299, 300 no long-term clinical trials have been performed.”
From Dietary and Policy Priorities for Cardiovascular Disease, Diabetes, and Obesity: A Comprehensive Review (2016) · cites this paper as [299]

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Cardioprotective actions of two bioflavonoids, quercetin and rutin, in experimental myocardial infarction in both normal and streptozotocin-induced type I diabetic rats
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Oxidative and nitrosative stress induces peroxiredoxins in pancreatic beta cells
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Flavonoid inhibition of the human neutrophil NADPH-oxidase
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Quercetin-Supplemented Diets Lower Blood Pressure and Attenuate Cardiac Hypertrophy in Rats With Aortic Constriction
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Quercetin Inhibits eNOS, Microtubule Polymerization, and Mitotic Progression in Bovine Aortic Endothelial Cells
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Comparison of red wine extract and polyphenol constituents on endothelin-1 synthesis by cultured endothelial cells
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Vasorelaxant Effects of the Bioflavonoid Chrysin in Isolated Rat Aorta
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Pretreatment with a combination of quercetin and α-tocopherol ameliorates adenosine triphosphatases and lysosomal enzymes in myocardial infarcted rats
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Self-citation
Involvement of thromboxane A2 in the endothelium‐dependent contractions induced by myricetin in rat isolated aorta
Jiménez, R., Andriambeloson, E., Duarte, J., Andriantsitohaina, R., Jiménez, J., Pérez‐Vizcaíno, F., Zarzuelo, A., & Tamargo, J. L. (1999) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0702694 · Cited by 30 · see citing works
Self-citation
Activation of EpRE-mediated gene transcription by quercetin glucuronides depends on their deconjugation
Lee-Hilz, Y. Y., Stolaki, M., van Berkel, W. J. H., Aarts, J. M. M. J. G., & Rietjens, I. M. C. M. (2008) · Food and Chemical Toxicology · doi:10.1016/j.fct.2008.02.010 · Cited by 30 · see citing works
Glucuronidated Metabolites of the Flavonoid Quercetin do not Auto-Oxidise, do not Generate Free Radicals and do not Decrease Nitric Oxide Bioavailability
Lodi, F., Jiménez, R., Menéndez, C., Needs, P. W., Duarte, J., & Pérez‐Vizcaíno, F. (2008) · Planta Medica · doi:10.1055/s-2008-1074525 · Cited by 25 · see citing works
Self-citation
Quercetin is bioavailable from a single ingestion of grape juice
Dávalos, A., Castilla, P., Gómez‐Cordovés, C., & Bartolomé, B. (2006) · International Journal of Food Sciences and Nutrition · doi:10.1080/09637480600858662 · Cited by 23 · see citing works
Term "Vitamin P" Recommended to be Discontinued
Vickery, H. B., Nelson, E. M., Almquist, H. J., & Elvehjem, C. A. (1950) · Science · doi:10.1126/science.112.2917.628 · Cited by 21 · see citing works
Hypoxia modulates gene expression of IP3 receptors in rodent cerebellum
Jurkovičová, D., Kopáček, J., Štefánik, P., Kubovčáková, L., Zahradníková, A., Zahradníková, A., Pastoreková, S., & Križanová, O. (2007) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-007-0214-6 · Cited by 20 · see citing works
Inhibition of the different cyclic nucleotide phosphodiesterase isoforms separated from rat brain by flavonoid compounds.
Picq, M., Dubois, M., Prigent, A., Némoz, G., & Pachéco, H. (1989) · PubMed · Cited by 11 · see citing works
Term "Vitamin P" Recommended to be Discontinued
Vickery, H. B., Nelson, E. M., Almquist, H. J., & Elvehjem, C. A. (1950) · Science · doi:10.1126/science.112.2917.628.a · Cited by 5 · see citing works

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Sorted by citations

Dietary and Policy Priorities for Cardiovascular Disease, Diabetes, and Obesity: A Comprehensive Review
Mozaffarian, D. (2016) · Circulation · doi:10.1161/circulationaha.115.018585 · Cited by 2,216 · see citing works
RETRACTED: Quercetin: A flavonol with multifaceted therapeutic applications?
D’Andrea, G. (2015) · Fitoterapia · doi:10.1016/j.fitote.2015.09.018 · Cited by 729 · see citing works
Retracted
Bioactive compounds in banana and their associated health benefits – A review
Singh, B., Singh, J. P., Kaur, A., & Singh, N. (2016) · Food Chemistry · doi:10.1016/j.foodchem.2016.03.033 · Cited by 531 · see citing works
Therapeutic potential of quercetin as a cardiovascular agent
Patel, R. V., Mistry, B. M., Shinde, S. K., Syed, R., Singh, V., & Shin, H. (2018) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2018.06.053 · Cited by 506 · see citing works
A survey of modulation of gut microbiota by dietary polyphenols
Dueñas, M., Muñoz-González, I., Cueva, C., Jiménez-Girón, A., Sánchez-Patán, F., Santos-Buelga, C., Moreno-Arribas, M. V., & Bartolomé, B. (2015) · BioMed Research International · doi:10.1155/2015/850902 · Cited by 396 · see citing works
“Indeed, a range of pharmacological effects have been demonstrated for different phenolic compounds—especially flavonoids—through in vitro, ex vivo and animal assays [8, 9].”
Background
Flavonoid intake and risk of CVD: a systematic review and meta-analysis of prospective cohort studies
Wang, X., Ouyang, Y., Liu, J., & Zhao, G. (2013) · British Journal Of Nutrition · doi:10.1017/s000711451300278x · Cited by 384 · see citing works
“Flavonols may protect coronary vessels by preventing atherosclerosis, hypertension and endothelial dysfunction((50)).”
Dietary phytochemicals and their potential effects on obesity: A review
González-Castejón, M., & Rodríguez‐Casado, A. (2011) · Pharmacological Research · doi:10.1016/j.phrs.2011.07.004 · Cited by 375 · see citing works
Tea: A new perspective on health benefits
Pinto, M. D. S. (2013) · Food Research International · doi:10.1016/j.foodres.2013.01.038 · Cited by 296 · see citing works
Research trends in flavonoids and health
Pérez‐Vizcaíno, F., & Fraga, C. G. (2018) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2018.03.022 · Cited by 284 · see citing works
The Health Potential of Fruits and Vegetables Phytochemicals: Notable Examples
Rodríguez‐Casado, A. (2014) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2012.755149 · Cited by 267 · see citing works
“On the other hand, many studies also indicate a strong link between fruit and vegetable intake and a reduced risk for cardiovascular disease (Badimon et al., 2010; Perez-Vizcaino and Duarte, 2010; Finks et al., 2012; Vasanthi et al., 2012).”
Background
Red Wine Consumption and Cardiovascular Health
Castaldo, L., Narváez, A., Izzo, L., Graziani, G., Gaspari, A., Minno, G. D., & Ritieni, A. (2019) · Molecules · doi:10.3390/molecules24193626 · Cited by 264 · see citing works
“These compounds are known to play a wide range of biological activities and are considered the main active compounds within the flavonoids group [74].”
Background
Evolution of Phenolic Compounds from Color and Flavor Problems to Health Benefits
Soto‐Vaca, A., Gutierrez, A., Losso, J. N., Xu, Z., & Finley, J. W. (2012) · Journal of Agricultural and Food Chemistry · doi:10.1021/jf300861c · Cited by 238 · see citing works
Bioactive compounds in banana fruits and their health benefits
Sidhu, J. S., & Zafar, T. A. (2018) · Food Quality and Safety · doi:10.1093/fqsafe/fyy019 · Cited by 230 · see citing works
Dietary Flavonoids and Cardiovascular Disease: A Comprehensive Dose–Response Meta‐Analysis
Micek, A., Godos, J., Rio, D. D., Galvano, F., & Grosso, G. (2021) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.202001019 · Cited by 226 · see citing works
Green extraction techniques from fruit and vegetable waste to obtain bioactive compounds—A review
García, S. L. R., & Raghavan, V. (2021) · Critical reviews in food science and nutrition · doi:10.1080/10408398.2021.1901651 · Cited by 164 · see citing works
Effects of Apigenin on RBL-2H3, RAW264.7, and HaCaT Cells: Anti-Allergic, Anti-Inflammatory, and Skin-Protective Activities
Park, C.-H., Min, S.-Y., Yu, H.-W., Kim, K., Kim, S. Y., Lee, H., Kim, J., & Park, Y. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21134620 · Cited by 191 · see citing works
“Moreover, 100 μM apigenin could inhibit NO production in RAW264 cells at a level similar to that observed with quercetin (15 μM) [62], which exhibits excellent inhibitory activity on NO production (Figure 2a).”
Background
Polyphenol protection and treatment of hypertension
Hügel, H., Jackson, N., May, B. H., Zhang, A. L., & Xue, C. C. (2016) · Phytomedicine · doi:10.1016/j.phymed.2015.12.012 · Cited by 187 · see citing works
Potential Role of Seaweed Polyphenols in Cardiovascular-Associated Disorders
Gómez‐Guzmán, M., Rodríguez‐Nogales, A., Algieri, F., & Gálvez, J. (2018) · Marine Drugs · doi:10.3390/md16080250 · Cited by 185 · see citing works
“Of note, flavonoids possess antioxidant properties that ameliorate vascular dysfunction via increasing nitric oxide (NO) bioavailability and endothelium-dependent vasorelaxation [126].”
Background
Study of the dynamic changes in the non-volatile chemical constituents of black tea during fermentation processing by a non-targeted metabolomics approach
Tan, J., Dai, W., Lü, M., Lv, H., Guo, L., Zhang, Y., Zhu, Y., Peng, Q., & Lin, Z. (2015) · Food Research International · doi:10.1016/j.foodres.2015.11.018 · Cited by 181 · see citing works
Actions of Quercetin, a Polyphenol, on Blood Pressure
Marunaka, Y., Marunaka, R., Sun, H., Yamamoto, T., Kanamura, N., Inui, T., & Taruno, A. (2017) · Molecules · doi:10.3390/molecules22020209 · Cited by 177 · see citing works
A Comprehensive Review on Nutritional Value, Medicinal Uses, and Processing of Banana
Ranjha, M. M. A. N., Irfan, S., Nadeem, M., & Mahmood, S. (2022) · Food Reviews International · doi:10.1080/87559129.2020.1725890 · Cited by 176 · see citing works
Electrospun chitosan oligosaccharide/polycaprolactone nanofibers loaded with wound-healing compounds of Rutin and Quercetin as antibacterial dressings
Zhou, L., Cai, L., Ruan, H., Zhang, L., Wang, J., Jiang, H., Wu, Y., Feng, S., & Chen, J. (2021) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2021.05.031 · Cited by 162 · see citing works
Does childhood nutrition influence adult cardiovascular disease risk?—Insights from the Young Finns Study
Kaikkonen, J., Mikkilä, V., Magnussen, C. G., Juonala, M., Viikari, J. S. A., & Raitakari, O. T. (2012) · Annals of Medicine · doi:10.3109/07853890.2012.671537 · Cited by 156 · see citing works
Dynamic changes in the metabolite profile and taste characteristics of Fu brick tea during the manufacturing process
Li, Q., Jin, Y., Jiang, R., Xu, Y., Zhang, Y., Luo, Y., Huang, J., Wang, K., & Liu, Z. (2020) · Food Chemistry · doi:10.1016/j.foodchem.2020.128576 · Cited by 157 · see citing works
Brain “fog,” inflammation and obesity: key aspects of neuropsychiatric disorders improved by luteolin
Theoharides, T. C. (2015) · Frontiers in Neuroscience · doi:10.3389/fnins.2015.00225 · Cited by 154 · see citing works
“Flavonoids have been proposed as possible therapeutic agents for CAD (Kempuraj et al., 2005; Perez-Vizcaino and Duarte, 2010; Yap et al., 2010).”
Background
Kaempferol attenuates cognitive deficit via regulating oxidative stress and neuroinflammation in an ovariectomized rat model of sporadic dementia
Babaei, P., Kouhestani, S., & Jafari, A. (2018) · Neural Regeneration Research · doi:10.4103/1673-5374.238714 · Cited by 155 · see citing works
“, 2015), Parkinson (Li and Pu, 2011) and cardiovascular diseases (Perez-Vizcaino and Duarte, 2010).”
Polyphenol Supplementation as a Complementary Medicinal Approach to Treating Inflammatory Bowel Disease
Biasi, F., Astegiano, M., Maina, M., Leonarduzzi, G., & Poli, G. (2011) · Current Medicinal Chemistry · doi:10.2174/092986711797535263 · Cited by 152 · see citing works
“Most clinical studies on polyphenols examine the possibility of reducing the risk of developing different cardiovascular diseases, such as atherosclerosis, obesity and insulin resistance, myocardial infarction, and preventing cancer [73].”
Background
Factors modulating bioavailability of quercetin-related flavonoids and the consequences of their vascular function
Terao, J. (2017) · Biochemical Pharmacology · doi:10.1016/j.bcp.2017.03.021 · Cited by 149 · see citing works
“Quercetin and related flavonoids have long been suggested to possess beneficial effects on vascular function leading to protective role in atherosclerotic events [77,78].”
Background
A Structurally‐Tunable 3‐Hydroxyflavone Motif for Visible Light‐Induced Carbon Monoxide‐Releasing Molecules (CORMs)
Anderson, S. N., Richards, J. M., Esquer, H., Benninghoff, A. D., Arif, A. M., & Berreau, L. M. (2015) · ChemistryOpen · doi:10.1002/open.201500167 · Cited by 134 · see citing works
The flavonoid paradox: conjugation and deconjugation as key steps for the biological activity of flavonoids
Pérez‐Vizcaíno, F., Duarte, J., & Santos‐Buelga, C. (2012) · Journal of the Science of Food and Agriculture · doi:10.1002/jsfa.5697 · Cited by 134 · see citing works
Self-citation
A New Database Facilitates Characterization of Flavonoid Intake, Sources, and Positive Associations with Diet Quality among US Adults ,
Sebastian, R. S., Enns, C. W., Goldman, J. D., Martin, C., Steinfeldt, L. C., Murayi, T., & Moshfegh, A. J. (2015) · Journal of Nutrition · doi:10.3945/jn.115.213025 · Cited by 133 · see citing works
Potential health benefits of garden pea seeds and pods: A review
Kumari, T., & Deka, S. C. (2021) · Legume Science · doi:10.1002/leg3.82 · Cited by 132 · see citing works
“…carotenoids, vitamin C and antioxidants which lessen the chances of heart stroke by modifying cardiometabolic risks and various diseases related to heart because of their ability to protect the cells from damage (Papandreou et al., 2019; Perez-Vizcaino & Duarte, 2010; Voutilainen et al., 2006).”
Background
Dietary polyphenols and their roles in fat browning
Silvester, A. J., Aseer, K. R., & Yun, J. W. (2018) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2018.09.028 · Cited by 131 · see citing works
First Web-Based Database on Total Phenolics and Oxygen Radical Absorbance Capacity (ORAC) of Fruits Produced and Consumed within the South Andes Region of South America
Speisky, H., López‐Alarcón, C., Gómez, M., Fuentes, J., & Sandoval-Acuña, C. (2012) · Journal of Agricultural and Food Chemistry · doi:10.1021/jf205167k · Cited by 128 · see citing works
Vascular deconjugation of quercetin glucuronide: The flavonoid paradox revealed?
Menéndez, C., Dueñas, M., Galindo, P., González‐Manzano, S., Jiménez, R., Moreno, L., Zarzuelo-Romero, M. J., Rodríguez‐Gómez, I., Duarte, J., Santos‐Buelga, C., et al. (2011) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201100378 · Cited by 127 · see citing works
“These data are supported by multiple animal studies showing that quercetin and related flavonoids exert a wide range of biological effects both in vitro and in vivo [4].”
ResultSelf-citation
Glucuronidated Quercetin Lowers Blood Pressure in Spontaneously Hypertensive Rats via Deconjugation
Galindo, P., Rodríguez‐Gómez, I., González‐Manzano, S., Dueñas, M., Jiménez, R., Menéndez, C., Vargas, F., Tamargo, J. L., Santos‐Buelga, C., Pérez‐Vizcaíno, F., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0032673 · Cited by 127 · see citing works
“for the observed protective effects of dietary flavonoids with respect to cardiovascular diseases [5].”
BackgroundSelf-citation
Modulation of nitric oxide by flavonoids
Duarte, J., Francisco, V., & Pérez‐Vizcaíno, F. (2014) · Food & Function · doi:10.1039/c4fo00144c · Cited by 127 · see citing works
Self-citation
Role of flavonoids in thrombotic, cardiovascular, and inflammatory diseases
Vazhappilly, C. G., Ansari, S. A., Al-Jaleeli, R., Al-Azawi, A. M., Ramadan, W. S. H., Menon, V., Hodeify, R. F., Siddiqui, S. S., Merheb, M. M., Matar, R., et al. (2019) · Inflammopharmacology · doi:10.1007/s10787-019-00612-6 · Cited by 124 · see citing works
Kaempferol inhibits thrombosis and platelet activation
Choi, J., Park, S., Kim, S.-J., & Kim, S. (2015) · Biochimie · doi:10.1016/j.biochi.2015.06.001 · Cited by 122 · see citing works
The UPR in atherosclerosis
Zhou, A. X., & Tabas, I. (2013) · Seminars in Immunopathology · doi:10.1007/s00281-013-0372-x · Cited by 121 · see citing works
“Quercetin and its related flavonols exert multiple functions in in vitro studies, including endothelium-independent vasodilator effects, protective effect on nitric oxide and endothelial function under oxidative stress, suppression of platelet aggregation, inhibition of LDL oxidation, and reduction of adhesion molecul…”
Molecular and physiological actions of quercetin: need for clinical trials to assess its benefits in human disease
Miles, S. L., McFarland, M., & Niles, R. M. (2014) · Nutrition Reviews · doi:10.1111/nure.12152 · Cited by 114 · see citing works
High-nitrate vegetable diet increases plasma nitrate and nitrite concentrations and reduces blood pressure in healthy women
Ashworth, A., Mitchell, K., Blackwell, J. R., Vanhatalo, A., & Jones, A. M. (2015) · Public Health Nutrition · doi:10.1017/s1368980015000038 · Cited by 109 · see citing works
“In addition, biologically active polyphenols, such as quercetin, have been shown to reduce BP((14,15)), potentially via increasing the biological activity of nitric oxide and protecting it from oxidation((16)).”
An overview and update on the epidemiology of flavonoid intake and cardiovascular disease risk
Parmenter, B. H., Croft, K. D., Hodgson, J. M., Dalgaard, F., Bondonno, C. P., Lewis, J. R., Cassidy, A., Scalbert, A., & Bondonno, N. P. (2020) · Food & Function · doi:10.1039/d0fo01118e · Cited by 109 · see citing works
The activation of mitochondrial BK potassium channels contributes to the protective effects of naringenin against myocardial ischemia/reperfusion injury
Testai, L., Martelli, A., Marino, A., D’Antongiovanni, V., Ciregia, F., Giusti, L., Lucacchini, A., Chericoni, S., Breschi, M. C., & Calderone, V. (2013) · Biochemical Pharmacology · doi:10.1016/j.bcp.2013.03.018 · Cited by 107 · see citing works
“This phytochemical class has been intensely investigated after the early publication of convincing epidemiological studies, indicating a significant association between the dietary intake of flavonoids and a decreased risk of important pathological disorders, such as the cardiovascular diseases [28–33].”
Background
Bond dissociation free energy as a general parameter for flavonoid radical scavenging activity
Stepanić, V., Gall‐Tros̆elj, K., Lučić, B., Marković, Z., & Amić, D. (2013) · Food Chemistry · doi:10.1016/j.foodchem.2013.03.072 · Cited by 107 · see citing works
Transcriptional regulation of flavonol biosynthesis in plants
Cao, Y., Mei, Y., Zhang, R., Zhong, Z., Yang, X., Xu, C., Chen, K., & Li, X. (2024) · Horticulture Research · doi:10.1093/hr/uhae043 · Cited by 107 · see citing works
“Moreover, numerous studies have reported that flavonols have strong antioxidant activity and play important roles in preventing chronic non-communicable diseases such as cancers, cardiovascular diseases, and diabetes in humans [9–14].”
Background
Transgenic rice seed synthesizing diverse flavonoids at high levels: a new platform for flavonoid production with associated health benefits
Ogo, Y., Ozawa, K., Ishimaru, T., Murayama, T., & Takaiwa, F. (2013) · Plant Biotechnology Journal · doi:10.1111/pbi.12064 · Cited by 105 · see citing works
Natural flavonols: actions, mechanisms, and potential therapeutic utility for various diseases
Mahmud, A. R., Ema, T. I., Siddiquee, M. F. R., Shahriar, A., Ahmed, H., Mosfeq-Ul-Hasan, M., Rahman, N., Islam, R., Uddin, M. R., & Mizan, M. F. R. (2023) · Beni-Suef University Journal of Basic and Applied Sciences · doi:10.1186/s43088-023-00387-4 · Cited by 106 · see citing works
Untargeted metabolomics coupled with chemometrics approach for Xinyang Maojian green tea with cultivar, elevation and processing variations
Wang, H., Cao, X., Yuan, Z., & Guo, G. (2021) · Food Chemistry · doi:10.1016/j.foodchem.2021.129359 · Cited by 107 · see citing works
Raman spectroscopy and machine-learning for edible oils evaluation
Berghian-Groșan, C., & Măgdaş, D. A. (2020) · Talanta · doi:10.1016/j.talanta.2020.121176 · Cited by 100 · see citing works
Cardioprotective effects of different flavonoids against myocardial ischaemia/reperfusion injury in Langendorff-perfused rat hearts
Testai, L., Martelli, A., Cristofaro, M., Breschi, M. C., & Calderone, V. (2013) · Journal of Pharmacy and Pharmacology · doi:10.1111/jphp.12032 · Cited by 100 · see citing works
Phytochemicals as novel agents for the induction of browning in white adipose tissue
Azhar, Y., Parmar, A., Miller, C. N., Samuels, J. S., & Rayalam, S. (2016) · Nutrition & Metabolism · doi:10.1186/s12986-016-0150-6 · Cited by 99 · see citing works
Metabolomics Investigation Reveals That 8-C N-Ethyl-2-pyrrolidinone-Substituted Flavan-3-ols Are Potential Marker Compounds of Stored White Teas
Dai, W., Tan, J., Lü, M., Zhu, Y., Li, P., Peng, Q., Guo, L., Zhang, Y., Xie, D., Hu, Z., et al. (2018) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.8b02038 · Cited by 96 · see citing works
Direct comparison of metabolic health effects of the flavonoids quercetin, hesperetin, epicatechin, apigenin and anthocyanins in high-fat-diet-fed mice
den Hil, E. F. H.-V., van Schothorst, E. M., van der Stelt, I., Swarts, H. J. M., Vliet, M., Amolo, T., Vervoort, J. J. M., Venema, D. P., Hollman, P. C. H., Rietjens, I. M. C. M., et al. (2015) · Genes & Nutrition · doi:10.1007/s12263-015-0469-z · Cited by 96 · see citing works
“The observed potential beneficial effects of flavonoids in humans are mostly based on studies using flavonoid-rich foods or extracts (Kim et al. 2011; Perez-Vizcaino and Duarte 2010).”
Background
Reaction time and DPPH concentration influence antioxidant activity and kinetic parameters of bioactive molecules and plant extracts in the reaction with the DPPH radical
Fadda, A., Serra, M., Molinu, M. G., Azara, E., Barberis, A., & Sanna, D. (2014) · Journal of Food Composition and Analysis · doi:10.1016/j.jfca.2014.06.006 · Cited by 94 · see citing works
Quercetin ameliorates glucose and lipid metabolism and improves antioxidant status in postnatally monosodium glutamate-induced metabolic alterations
Seiva, F. R. F., Chuffa, L. G. D. A., Braga, C. P., Amorim, J. P. D. A., & Fernandes, A. A. H. (2012) · Food and Chemical Toxicology · doi:10.1016/j.fct.2012.07.009 · Cited by 93 · see citing works
“More directly, MSG is thought to cause cardiovascular damage, while quercetin administration (Perez-Vizcaino and Duarte, 2010) has improved this condition.”
Background
Antioxidant Potential of Polyphenolic Compounds, Sources, Extraction, Purification and Characterization Techniques: A Focused Review
Ahmad, Z., Rauf, A., Orhan, İ. E., Mubarak, M. S., Akram, Z., Islam, M. R., Imran, M., Edis, Z., Kondapavuluri, B. K., Thangavelu, L. P., et al. (2025) · Food Science & Nutrition · doi:10.1002/fsn3.71259 · Cited by 88 · see citing works
The flavonoid quercetin induces acute vasodilator effects in healthy volunteers: Correlation with beta-glucuronidase activity
Perez, A., González‐Manzano, S., Jiménez, R., Pérez-Abud, R., Haro, J. M., Osuna, A., Santos‐Buelga, C., Duarte, J., & Pérez‐Vizcaíno, F. (2014) · Pharmacological Research · doi:10.1016/j.phrs.2014.07.005 · Cited by 88 · see citing works
“…(IISGM), Spain r t i c l e i n f o rticle history: eceived 13 May 2014 eceived in revised form 11 July 2014 ccepted 17 July 2014 vailable online 27 July 2014 eywords: uercetin asodilation uman a b s t r a c t Quercetin exerts vasodilator, antiplatelet and antiproliferative effects and reduces…”
BackgroundSelf-citation
In vitro and in vivo structure and activity relationship analysis of polymethoxylated flavonoids: Identifying sinensetin as a novel antiangiogenesis agent
Lam, I. K., Alex, D., Wang, Y., Liu, P., Liu, A., Du, G., & Lee, S. M. (2012) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201100680 · Cited by 87 · see citing works
“Epidemiological and experimental in vitro and in vivo evidence points to a possible protective effect of flavonoids against human cardiovascular diseases and cancer risks [9, 10].”
Background
Quercetin suppresses inflammation by reducing ERK1/2 phosphorylation and NF kappa B activation in Leptin-induced Human Umbilical Vein Endothelial Cells (HUVECs)
Indra, M. R., Karyono, S., Ratnawati, R., & Malik, S. G. (2013) · BMC Research Notes · doi:10.1186/1756-0500-6-275 · Cited by 87 · see citing works
“Quercetin is one of the most widely distributed flavonoids in fruits, vegetables, tea and wine [23], reported to have anti-inflammatory properties, and might act as health-promoting substances [24,25].”
Background
The beneficial health effects of flavonoids on the cardiovascular system: Focus on K+ channels
Fusi, F., Trezza, A., Tramaglino, M., Sgaragli, G., Saponara, S., & Spiga, O. (2020) · Pharmacological Research · doi:10.1016/j.phrs.2019.104625 · Cited by 86 · see citing works
Quercetin postconditioning attenuates myocardial ischemia/reperfusion injury in rats through the PI3K/Akt pathway
Wang, Y., Zhang, Z. Z., Wu, Y., Ke, J., He, X., & Wang, Y. (2013) · Brazilian Journal of Medical and Biological Research · doi:10.1590/1414-431x20133036 · Cited by 85 · see citing works
“Que manifests a wide range of beneficial biological activites and can mediate cardioprotective effects (7,23).”
Background
Cardiovascular Effects of Flavonoids
Sánchez, M., Romero, M., Gómez‐Guzmán, M., Tamargo, J. L., Pérez‐Vizcaíno, F., & Duarte, J. (2018) · Current Medicinal Chemistry · doi:10.2174/0929867326666181220094721 · Cited by 85 · see citing works
Self-citation
Updates on naringinase: structural and biotechnological aspects
Puri, M. (2011) · Applied Microbiology and Biotechnology · doi:10.1007/s00253-011-3679-3 · Cited by 83 · see citing works
Stress triggers coronary mast cells leading to cardiac events
Alevizos, M., Karagkouni, A., Panagiotidou, S., Vasiadi, M., & Theoharides, T. C. (2013) · Annals of Allergy Asthma & Immunology · doi:10.1016/j.anai.2013.09.017 · Cited by 83 · see citing works
The Flavonoid Quercetin Reverses Pulmonary Hypertension in Rats
Morales‐Cano, D., Menéndez, C., Moreno, E., Moral‐Sanz, J., Barreira, B., Galindo, P., Pandolfi, R., Jiménez, R., Moreno, L., Cogolludo, A. L., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0114492 · Cited by 82 · see citing works
“Several studies using various animal models provide support for the observed protective effects of dietary flavonoids with respect to cardiovascular diseases [12].”
ResultSelf-citation
Systemic and cerebral exposure to and pharmacokinetics of flavonols and terpene lactones after dosing standardized G inkgo biloba leaf extracts to rats via different routes of administration
Chen, F., Li, L., Xu, F., Sun, Y., Du, F., Ma, X., Zhong, C., Li, X., Wang, F., Zhang, N., et al. (2013) · British Journal of Pharmacology · doi:10.1111/bph.12285 · Cited by 81 · see citing works
“The majority of pharmacological assessments have been performed on the flavonol aglycones (Perez-Vizcaino and Duarte, 2010), rather than those ginkgo Table 5 Excretory data of total flavonols and terpene lactones after an i.”
Background
Biology in Bloom: A Primer on the Arabidopsis thaliana Model System
Woodward, A. W., & Bartel, B. (2018) · Genetics · doi:10.1534/genetics.118.300755 · Cited by 81 · see citing works
“Flavonol intake is correlated with markers of cardiovascular health (Perez-Vizcaino and Duarte 2010), so increasing crop flavonol content is an attractive ambition.”
Background
Antibacterial activity of quercetin on oral infectious pathogens
Shu, Y. (2011) · African Journal of Microbiology Research · doi:10.5897/ajmr11.849 · Cited by 82 · see citing works
“…studies have demonstrated that it had obvious pharmaceutical effects of anti-tumor (Feng et al., 2011), antioxidation (Chondrogianni et al., 2010), anti-inflammatory (Yamaguchi and Weitzmann, 2011), cardiovascular protection (Perez-Vizcaino and Duarte, 2010) and anti-viral (Mahmood et al., 1996).”
Background
Quercetin and Its Role in Chronic Diseases
Oboh, G., Ademosun, A. O., & Ogunsuyi, O. B. (2016) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-41342-6_17 · Cited by 78 · see citing works
Flavonoid quercetin–methotrexate combination inhibits inflammatory mediators and matrix metalloproteinase expression, providing protection to joints in collagen-induced arthritis
Haleagrahara, N., Hodgson, K., Miranda‐Hernandez, S., Hughes, S. D., Kulur, A. B., & Ketheesan, N. (2018) · Inflammopharmacology · doi:10.1007/s10787-018-0464-2 · Cited by 78 · see citing works
“Recent studies have demonstrated that this flavonoid plays a significant role in modulating inflammatory processes associated with cardiovascular and metabolic disorders (Panchal et al. 2012; Perez-Vizcaino and Duarte 2010).”
Background
Dietary flavonoids are neuroprotective through Nrf2-coordinated induction of endogenous cytoprotective proteins
Leonardo, C. C., & Doré, S. (2011) · Nutritional Neuroscience · doi:10.1179/1476830511y.0000000013 · Cited by 77 · see citing works
Role of MAPK/NF-κB pathway in cardioprotective effect of Morin in isoproterenol induced myocardial injury in rats
Verma, V. K., Malik, S., Narayanan, S. P., Mutneja, E., Sahu, A. K., Bhatia, J., & Arya, D. S. (2019) · Molecular Biology Reports · doi:10.1007/s11033-018-04575-9 · Cited by 76 · see citing works
Flavonoids as potential anti-platelet aggregation agents: from biochemistry to health promoting abilities
Sharifi‐Rad, J., Quispe, C., Shaheen, S., Haouari, M. E., Azzini, E., Butnariu, M., Sărac, I., Pentea, M., Ramírez‐Alarcón, K., Martorell, M., et al. (2021) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2021.1924612 · Cited by 76 · see citing works
“Similar results were stated in a series of experiments, that Quercetin has also been subject of several studies for its anti-platelet effects (Mosawy et al. 2013a, 2013b, 2014; Perez-Vizcaino and Duarte 2010).”
Result
A critical review on quercetin bioflavonoid and its derivatives: Scope, synthesis, and biological applications with future prospects
Udaya Rajesh, R., & Sangeetha, D. (2023) · Arabian Journal of Chemistry · doi:10.1016/j.arabjc.2023.104881 · Cited by 77 · see citing works
Effect of onion peel extract on endothelial function and endothelial progenitor cells in overweight and obese individuals
Choi, E.-Y., Lee, H., Woo, J. S., Jang, H. H., Hwang, S. J., Kim, H. S., Kim, W., Kim, Y.-S., Choue, R., Cha, Y.-J., et al. (2015) · Nutrition · doi:10.1016/j.nut.2015.04.020 · Cited by 74 · see citing works
“Quercetin derivatives present in onions are regarded as the most important flavonoids for improving inflammatory reaction and endothelial dysfunction in many animal and human studies [10–13].”
Background
Flavonol intake and stroke risk: A meta-analysis of cohort studies
Wang, Z., Zhao, D., Nie, Z.-L., Zhao, H., Zhou, B., Gao, W. Q., Wang, L., & Yang, Z. (2013) · Nutrition · doi:10.1016/j.nut.2013.10.009 · Cited by 73 · see citing works
“They are present in considerable amounts in our habitual diet and exhibit a wide range of biological activities [3–5].”
Background
Adsorption and Recovery of Polyphenolic Flavonoids Using TiO2-Functionalized Mesoporous Silica Nanoparticles
Khan, M. A., Wallace, W. T., Islam, S. Z., Nagpure, S., Strzalka, J. W., Littleton, J. M., Rankin, S. E., & Knutson, B. L. (2017) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.7b09510 · Cited by 73 · see citing works
Cardioprotective effects of rhamnetin in H9c2 cardiomyoblast cells under H2O2-induced apoptosis
Park, E.-S., Kang, J. C., Jang, Y. C., Park, J. S., Jang, S. Y., Kim, D.-E., Kim, B., & Shin, H. (2014) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2014.02.019 · Cited by 71 · see citing works
Enzymatically Modified Isoquercitrin: Production, Metabolism, Bioavailability, Toxicity, Pharmacology, and Related Molecular Mechanisms
Owczarek, A., Magiera, A., & Olszewska, M. A. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232314784 · Cited by 71 · see citing works
Quercetin attenuates cardiomyocyte apoptosis via inhibition of JNK and p38 mitogen-activated protein kinase signaling pathways
Li, C., Wang, T., Zhang, C., Xuan, J., Su, C., & Wang, Y. (2015) · Gene · doi:10.1016/j.gene.2015.12.012 · Cited by 70 · see citing works
Kaempferol, Myricetin and Fisetin in Prostate and Bladder Cancer: A Systematic Review of the Literature
Crocetto, F., Zazzo, E. D., Buonerba, C., Aveta, A., Pandolfo, S. D., Barone, B., Trama, F., Caputo, V. F., Scafuri, L., Ferro, M., et al. (2021) · Nutrients · doi:10.3390/nu13113750 · Cited by 68 · see citing works
“Among these, flavonols, which are characterized by a distinctive hydroxyl group at the C3 carbon position [17], represent the most ubiquitous flavonoids present in food [18].”
Colonic fermentation of polyphenolics from Sea buckthorn ( Hippophae rhamnoides ) berries: Assessment of effects on microbial diversity by Principal Component Analysis
Attri, S., Sharma, K., Raigond, P., & Goel, G. (2017) · Food Research International · doi:10.1016/j.foodres.2017.11.032 · Cited by 68 · see citing works
“Indeed, a range of these potential benefits of polyphenols have been demonstrated through in vitro, ex vivo and animal assays (Perez-Vizcaino & Duarte, 2010; Spencer, Vafeiadou, Williams, & Vauzour, 2012).”
Background
Proatherogenic Macrophage Activities Are Targeted by the Flavonoid Quercetin
Lara-Guzmán, O. J., Tabares-Guevara, J. H., León-Varela, Y. M., Álvarez, R., Roldán, M., Sierra, J. A., Londoño‐Londoño, J., & Ramírez‐Pineda, J. R. (2012) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.112.196147 · Cited by 67 · see citing works
“Quercetin (3,3 ,4 ,5,7-pentahydroxyflavone) is a prototypical naturally occurring flavonoid that exhibits potent antioxidant activities and protects against various degenerative diseases (Chirumbolo, 2010; Perez-Vizcaino and Duarte, 2010; Mendoza and Burd, 2011).”
Background
Differential Impact of Flavonoids on Redox Modulation, Bioenergetics, and Cell Signaling in Normal and Tumor Cells: A Comprehensive Review
Kerimi, A., & Williamson, G. (2017) · Antioxidants and Redox Signaling · doi:10.1089/ars.2017.7086 · Cited by 66 · see citing works
“The absorption and biological effects of quercetin in humans are the subject of numerous reviews (55, 143, 190).”
Wine’s Phenolic Compounds and Health: A Pythagorean View
Visioli, F., Panaite, S.-A., & Tomé‐Carneiro, J. (2020) · Molecules · doi:10.3390/molecules25184105 · Cited by 66 · see citing works
“These compounds are known to play a wide range of biological activities and are considered the main active compounds within the flavonoids group [36,37].”
Background
Shining natural flavonols in sensing and bioimaging
Tong, C., Shi, F., Tong, X., Shi, S., Ali, I., & Guo, Y. (2021) · TrAC Trends in Analytical Chemistry · doi:10.1016/j.trac.2021.116222 · Cited by 65 · see citing works
PpMYB15 and PpMYBF1 Transcription Factors Are Involved in Regulating Flavonol Biosynthesis in Peach Fruit
Cao, Y., Xie, L., Ma, Y., Ren, C., Xing, M., Fu, Z., Wu, X., Yin, X.-R., Xu, C., & Li, X. (2018) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.8b04810 · Cited by 64 · see citing works
Epigenetic regulation of active Chinese herbal components for cancer prevention and treatment: A follow-up review
Huang, Z., Huang, Q., Ji, L., Wang, Y., Qi, X., Liu, L., Liu, Z., & Lu, L. (2016) · Pharmacological Research · doi:10.1016/j.phrs.2016.09.023 · Cited by 62 · see citing works
Quercetin Inhibits Vascular Endothelial Growth Factor-Induced Choroidal and Retinal Angiogenesis in vitro
Li, F., Bai, Y., Zhao, M., Huang, L., Li, S., Li, X., & Chen, Y. (2015) · Ophthalmic Research · doi:10.1159/000369824 · Cited by 59 · see citing works
Dietary flavonoid intake and the risk of stroke: a dose-response meta-analysis of prospective cohort studies
Tang, Z., Li, M., Zhang, X., & Hou, W.-S. (2016) · BMJ Open · doi:10.1136/bmjopen-2015-008680 · Cited by 58 · see citing works
“A third mechanism is the protective action of flavonoids on the anti-inflammatory responses in the brain, which may be attributable to lipid raft disruption and antioxidant effects.(46) Because the flavonoids are very diverse regarding their bioavailability and bioactivity, the rationale for assuming that intakes of a…”
Background
Plant phytochemicals as new potential drugs for immune disorders and cancer therapy: really a promising path?
Chirumbolo, S. (2012) · Journal of the Science of Food and Agriculture · doi:10.1002/jsfa.5670 · Cited by 58 · see citing works
Protective effect of dietary flavonoid quercetin against lipemic-oxidative hepatic injury in hypercholesterolemic rats
Mariee, A. D., Abd‐Allah, G. M., & El-Beshbishy, H. A. (2012) · Pharmaceutical Biology · doi:10.3109/13880209.2012.655424 · Cited by 58 · see citing works
“Most studies have shown that quercetin has no beneficial effect on the plasma lipid profile (Yamamoto & Oue, 2006: Perez-Vizcaino & Duarte, 2010; Egert et al., 2010; Zhao et al., 2011).”
Background
Impact of Nutrition on Pulmonary Arterial Hypertension
Callejo, M., Barberà, J. A., Duarte, J., & Pérez‐Vizcaíno, F. (2020) · Nutrients · doi:10.3390/nu12010169 · Cited by 58 · see citing works
“Many studies have analyzed the influence of polyphenols in human heath [94], and more especially its positive role against cardiovascular diseases [95,96].”
BackgroundSelf-citation
The flavonoid scaffold as a template for the design of modulators of the vascular Cav1.2 channels
Saponara, S., Carosati, E., Mugnai, P., Sgaragli, G., & Fusi, F. (2011) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2011.01476.x · Cited by 57 · see citing works
“It is conceivable that molecules such as quercetin, capable of generating H2O2 (Perez-Vizcaino and Duarte, 2010), may modulate Cav1.”
Background
Monitoring of phytochemicals in fresh and fresh-cut vegetables: A comparison
Alarcón-Flores, M. I., Romero‐González, R., Vidal, J. L. M., González, F. J. E., & Frenich, A. G. (2013) · Food Chemistry · doi:10.1016/j.foodchem.2013.07.065 · Cited by 56 · see citing works
Quercetin and its metabolites inhibit the membrane NADPH oxidase activity in vascular smooth muscle cells from normotensive and spontaneously hypertensive rats
Jiménez, R., López-Sepúlveda, R., Romero, M., Toral, M., Cogolludo, A. L., Pérez‐Vizcaíno, F., & Duarte, J. (2014) · Food & Function · doi:10.1039/c4fo00818a · Cited by 54 · see citing works
Self-citation
The Anticancer Potential of Plant-Derived Nutraceuticals via the Modulation of Gene Expression
Vrânceanu, M., Galimberti, D., Banc, R., Dragoş, O., Cozma-Petruț, A. P., Hegheş, S. C., Voștinaru, O., Cuciureanu, M. D., Stroia, C. M., Miere, D., et al. (2022) · Plants · doi:10.3390/plants11192524 · Cited by 59 · see citing works
Research Progress of Flavonoids Regulating Endothelial Function
Li, H., & Zhang, Q. (2023) · Pharmaceuticals · doi:10.3390/ph16091201 · Cited by 58 · see citing works
Dietary flavonoids intake and the risk of coronary heart disease: A dose-response meta-analysis of 15 prospective studies
Jiang, W., Wei, H., & He, B. (2014) · Thrombosis Research · doi:10.1016/j.thromres.2014.12.016 · Cited by 55 · see citing works
“No other uses without permission flavonoids group [6].”
Background

Therapeutic potential of quercetin as a cardiovascular agent
Patel, R. V., Mistry, B. M., Shinde, S. K., Syed, R., Singh, V., & Shin, H. (2018) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2018.06.053 · Cited by 506 · see citing works
Endothelial function and cardiovascular disease: Effects of quercetin and wine polyphenols
Pérez‐Vizcaíno, F., Duarte, J., & Andriantsitohaina, R. (2006) · Free Radical Research · doi:10.1080/10715760600823128 · Cited by 218 · see citing works
Self-citation
Q
Eskin, M., & Tamir, S. (2005) · CRC Press eBooks · doi:10.1201/9780203486856-18
Flavonoids and cardiovascular disease: Mechanisms involved in the cardioprotective effects of quercetin
Pérez‐Vizcaíno, F., Duarte, J. F., Cogolludo, A. L., Lodi, F., Jiménez, R., & Tamargo, J. L. (2008)
Self-citation
Targeting Cardiovascular Diseases by Flavonols: An Update
Kozłowska, A., & Szostak-Węgierek, D. E. (2022) · Nutrients · doi:10.3390/nu14071439 · Cited by 47 · see citing works

Authors: Perez-Vizcaino, F., & Duarte, J.
Affiliations: Universidad de Granada (ES)
ORCID: Duarte, Juan
Venue: Molecular Aspects of Medicine
Publisher: Elsevier BV
Published: 2010-12
Volume: 31
Issue: 6
Pages: 478-494
ISSN: 0098-2997 (ISSN-L)
DOI: 10.1016/j.mam.2010.09.002
OpenAlex: W2088383365
Cited by: 393
References: 164
Citations by year: 2026: 11 · 2025: 23 · 2024: 23 · 2023: 21 · 2022: 33 · 2021: 26 · 2020: 18 · 2019: 20 · 2018: 29 · 2017: 16 · 2016: 32 · 2015: 34 · 2014: 30 · 2013: 30 · 2012: 31
FWCI: 2.22
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Molecular Aspects of Medicine (publishedVersion)
PubMed (publishedVersion)
Funders: Spanish Ministerio de Ciencia y Tecnología (AGL2007-66108, SAF2008-03948, Red HERACLES RD06/0009)
Junta de Andalucía (P06-CTS-01555)
Topics: Health Sciences › Medicine › Biochemistry › Phytochemicals and Antioxidant Activities
Health Sciences › Medicine › Pharmacology › Flavonoids in Medical Research
Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Nutritional Studies and Diet
Keywords: flavonols, quercetin, cardiovascular disease, endothelial function, nitric oxide, oxidative stress, platelet aggregation, LDL oxidation, inflammation, antihypertensive effect, atherosclerosis, coronary artery disease, stroke, flavonoid metabolites, fruits and vegetables, antioxidant activity
MeSH terms: Animals, Antioxidants, Cardiovascular Diseases, Endothelium, Vascular, Humans, Muscle, Smooth, Vascular, Quercetin, Oxidative Stress, Flavonols

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