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

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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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Stress triggers coronary mast cells leading to cardiac events
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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 88
“Several studies using various animal models provide support for the observed protective effects of dietary flavonoids with respect to cardiovascular diseases [12].”
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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
“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 92
“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
“…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
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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
“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
Role of MAPK/NF-κB pathway in cardioprotective effect of Morin in isoproterenol induced myocardial injury in rats
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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
“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 80
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
“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
“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 74
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
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
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
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
“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
“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
“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 69
“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 71
“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].”
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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
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
Epigenetic regulation of active Chinese herbal components for cancer prevention and treatment: A follow-up review
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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
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
“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
Protective effect of dietary flavonoid quercetin against lipemic-oxidative hepatic injury in hypercholesterolemic rats
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“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 61
“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
“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
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Quercetin and its metabolites inhibit the membrane NADPH oxidase activity in vascular smooth muscle cells from normotensive and spontaneously hypertensive rats
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Self-citation
The Anticancer Potential of Plant-Derived Nutraceuticals via the Modulation of Gene Expression
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Research Progress of Flavonoids Regulating Endothelial Function
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Dietary flavonoids intake and the risk of coronary heart disease: A dose-response meta-analysis of 15 prospective studies
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“No other uses without permission flavonoids group [6].”
Background

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 (medical) › Phytochemicals and Antioxidant Activities
Health Sciences › Medicine › Pharmacology (medical) › 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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