Cited by 319Phytochemicals and Antioxidant ActivitiesNitric Oxide and Endothelin EffectsAntioxidant Activity and Oxidative Stress

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Potential role of dietary flavonoids in reducing microvascular endothelium vulnerability to oxidative and inflammatory insults ☆ ☆Mention of trade name, proprietary product, or specific equipment does not constitute a guarantee by the US Department of Agriculture and does not imply its approval to the exclusion of other products that may be suitable.

Youdim, Kuresh A., McDonald, Jane, Kalt, Wilhemina, Joseph, James A.·2002·The Journal of Nutritional Biochemistry

DOI 10.1016/s0955-2863(01)00221-2

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Abstract

Although antioxidant systems help control the level of reactive oxygen species they may be overwhelmed during periods of oxidative stress. Evidence suggests that oxidative stress components as well as inflammatory mediators may be involved in the pathogenesis of vascular disorders, where localized markers of oxidative damage have been found. In this regard we investigated the putative antioxidant and anti-inflammatory effects of blueberry and cranberry anthocyanins and hydroxycinnamic acids against H(2)O(2) and TNFalpha induced damage to human microvascular endothelial cells. Polyphenols from both berries were able to localize into endothelial cells subsequently reducing endothelial cells vulnerability to increased oxidative stress at both the membrane and cytosol level. Furthermore, berry polyphenols also reduced TNFalpha induced up-regulation of various inflammatory mediators (IL-8, MCP-1 and ICAM-1) involved in the recruitment of leukocytes to sites of damage or inflammation along the endothelium. In conclusion, polyphenols isolated from both blueberry and cranberry were able to afford protection to endothelial cells against stressor induced up-regulation of oxidative and inflammatory insults. This may have beneficial actions against the initiation and development of vascular diseases and be a contributing factor in the reduction of age-related deficits in neurological impairments previously reported by us.

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Devareddy, L., Hooshmand, S., Collins, J. K., Lucas, E. A., Chai, S. C., & Arjmandi, B. H. (2008) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2007.09.004 · Cited by 136
“A study conducted at Tufts University found that anthocyanins from blueberry show antioxidative and anti-inflammatory properties in treating human microvascular endothelial cells [36].”
Background
Effect of Grape Seed Extract and Quercetin on Cardiovascular and Endothelial Parameters in High‐Risk Subjects
Clifton, P. M. (2004) · BioMed Research International · doi:10.1155/s1110724304403088 · Cited by 132
“Polyphenols from blue and red berries reduce adhesion molecules in endothelial cells in vitro [35].”
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Polyphenolic Composition and Antioxidant Capacity of Extruded Cranberry Pomace
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Antioxidant and Cellular Activities of Anthocyanins and Their Corresponding Vitisins AStudies in Platelets, Monocytes, and Human Endothelial Cells
García-Alonso, M., Rimbach, G. H., Rivas-Gonzalo, J. C., & de Pascual‐Teresa, S. (2004) · Journal of Agricultural and Food Chemistry · doi:10.1021/jf035360v · Cited by 130
Feeding Rats Diets Enriched in Lowbush Blueberries for Six Weeks Decreases Ischemia-induced Brain Damage
Sweeney, M. I., Kalt-Torres, W., MacKinnon, S. L., Ashby, J., & Gottschall‐Pass, K. T. (2002) · Nutritional Neuroscience · doi:10.1080/1028415021000055970 · Cited by 129
“, 2000a) and endothelial cells (Youdim et al., 2002) exposed to hydrogen peroxide, a form of oxidative stress.”
Background
Purple Carrot (Daucus carota L.) Polyacetylenes Decrease Lipopolysaccharide-Induced Expression of Inflammatory Proteins in Macrophage and Endothelial Cells
Metzger, B. T., Barnes, D. M., & Reed, J. D. (2008) · Journal of Agricultural and Food Chemistry · doi:10.1021/jf073494t · Cited by 125
The bioavailability of raspberry anthocyanins and ellagitannins in rats
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Variation of Anthocyanin Content and Profile Throughout Fruit Development and Ripening of Highbush Blueberry Cultivars Grown at Two Different Altitudes
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Effect of Anthocyanin Fractions from Selected Cultivars of Georgia-Grown Blueberries on Apoptosis and Phase II Enzymes
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Phenolic Compounds: A Good Choice Against Chronic Degenerative Diseases
Luna-Guevara, M. L., Guevara, J. J. L., Hernández‐Carranza, P., Ruiz-Espinosa, H., & Ochoa‐Velasco, C. E. (2018) · Studies in natural products chemistry · doi:10.1016/b978-0-444-64179-3.00003-7 · Cited by 133
Anticancer activities of cranberry phytochemicals: An update
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Diets containing blueberry extract lower blood pressure in spontaneously hypertensive stroke-prone rats
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“When BB extracts were placed on human endothelial cells ex vivo, various markers of oxidative stress induced by H2O2 were reduced [30].”
Background
A single portion of blueberry (Vaccinium corymbosum L) improves protection against DNA damage but not vascular function in healthy male volunteers
Bo’, C. D., Riso, P., Campolo, J., Möller, P., Loft, S. H., Klimis‐Zacas, D. J., Brambilla, A., Rizzolo, A., & Porrini, M. (2013) · Nutrition Research · doi:10.1016/j.nutres.2012.12.009 · Cited by 115
Changes of Anthocyanins, Anthocyanidins, and Antioxidant Activity in Bilberry Extract during Dry Heating
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Intracellular Signaling Pathways Modulated by Phenolic Compounds: Application for New Anti-Inflammatory Drugs Discovery
Costa, G., Francisco, V., Lopes, M. C., Cruz, M. T., & Batista, M. T. (2012) · Current Medicinal Chemistry · doi:10.2174/092986712800672049 · Cited by 113
Endotoxin- and D-galactosamine-induced liver injury improved by the administration of Lactobacillus, Bifidobacterium and blueberry.
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Investigation of cytotoxic, apoptosis-inducing, genotoxic and protective effects of the flavonoid rutin in HTC hepatic cells
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Current clinical status on the preventive effects of cranberry consumption against urinary tract infections
Vasileiou, I., Katsargyris, Α., Theocharis, S. E., & Giaginis, C. (2013) · Nutrition Research · doi:10.1016/j.nutres.2013.05.018 · Cited by 107
“[37] Youdim KA, McDonald J, Kalt W, Joseph JA.”
Background
Analysis on the Nutrition Composition and Antioxidant Activity of Different Types of Sweet Potato Cultivars
Ji, H., Zhang, H., Li, H., & Li, Y. (2015) · Food and Nutrition Sciences · doi:10.4236/fns.2015.61017 · Cited by 116
“They have proved their excellent bioactivities such as antimutagenic [5] [6], radical scavenging [7], antihyperglycemic [8], hepatoprotective [9] [10], anticancer [11] [12], antioxidant activities [13]-[16], and chemopreventive activities [17] [18].”
Background
Berry anthocyanins and their aglycons inhibit monoamine oxidases A and B
Dreiseitel, A., Korte, G., Schreier, P. H., Oehme, A., Locher, S., Domani, M., Hajak, G., & Sand, P. G. (2009) · Pharmacological Research · doi:10.1016/j.phrs.2009.01.014 · Cited by 104
Exercise‐induced increases in inflammatory cytokines in muscle and blood of horses
Liburt, N. R., Adams, A. A., Betancourt, A., Horohov, D. W., & McKeever, K. H. (2010) · Equine Veterinary Journal · doi:10.1111/j.2042-3306.2010.00275.x · Cited by 104
Low-calorie cranberry juice supplementation reduces plasma oxidized LDL and cell adhesion molecule concentrations in men
Ruel, G., Pomerleau, S., Couture, P., Lemieux, S., Lamarche, B., & Couillard, C. (2008) · British Journal Of Nutrition · doi:10.1017/s0007114507811986 · Cited by 96
Anthocyanin Absorption, Metabolism, and Distribution from a Wild Blueberry-Enriched Diet (Vaccinium angustifolium) Is Affected by Diet Duration in the Sprague−Dawley Rat
Bo’, C. D., Ciappellano, S., Klimis‐Zacas, D. J., Martini, D., Gardana, C., Riso, P., & Porrini, M. (2009) · Journal of Agricultural and Food Chemistry · doi:10.1021/jf903472x · Cited by 94
Pomegranate protects against arsenic-induced p53-dependent ROS-mediated inflammation and apoptosis in liver cells
Choudhury, S., Ghosh, S., Mukherjee, S., Gupta, P., Bhattacharya, S., Adhikary, A., & Chattopadhyay, S. (2016) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2016.09.001 · Cited by 91
Dietary strategies to recover from exercise-induced muscle damage
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“They have been shown to reduced TNF-a induced up-regulation of inflammatory mediators in human micro-vascular endothelial cells (Youdim et al., 2002), to attenuate inflammatory gene expression in mice (DeFuria et al.”
Background
Wild Mediterranean Dietary Plants as Inhibitors of Pancreatic Lipase
Conforti, F., Perri, V., Menichini, F., Marrelli, M., Uzunov, D., Statti, G. A., & Menichini, F. (2011) · Phytotherapy Research · doi:10.1002/ptr.3603 · Cited by 88
“Recent studies have focused on health functions of phenolics, including flavonoids from fruit and vegetables (Saleem et al., 2002; You-dim et al., 2002; Qian et al., 2004; Chen et al., 2005, 2006; Soobrattee et al., 2005).”
Background
Probiotics and Blueberry Attenuate the Severity of Dextran Sulfate Sodium (DSS)-Induced Colitis
Osman, N., Adawi, D., Ahrné, S., Jeppsson, B. W., & Molin, G. (2008) · Digestive Diseases and Sciences · doi:10.1007/s10620-007-0174-x · Cited by 90
Evidences of the cardioprotective potential of fruits: The case of cranberries
Ruel, G., & Couillard, C. (2007) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.200600286 · Cited by 86
Acute Cardioprotective and Cardiotoxic Effects of Bilberry Anthocyanins in Ischemia–Reperfusion Injury: Beyond Concentration-Dependent Antioxidant Activity
Žiberna, L., Lunder, M., Može, Š., Vanzo, A., Tramer, F., Passamonti, S., & Drevenšek, G. (2010) · Cardiovascular Toxicology · doi:10.1007/s12012-010-9091-x · Cited by 87
Potential health benefits of anthocyanins in oxidative stress related disorders
Alam, M. A., Islam, P., Subhan, N., Rahman, M. M., Khan, F., Burrows, G. E., Nahar, L., & Sarker, S. D. (2021) · Phytochemistry Reviews · doi:10.1007/s11101-021-09757-1 · Cited by 99
“…frozen blueberries 94 participants were participated in a randomized, double blind, parallel groups, and placebo-controlled trial Intake of 12.5 g/day orally for 12 to 24 weeks trial Supplementation improved cognition (McNamara et al. 2018) disorders and atherosclerosis (Youdim et al. 2000, 2002).”
MethodInfluential
Free radical scavenging and antibacterial activities of southern Serbian red wines
Radovanović, A., Radovanović, B. C., & Jovančićević, B. (2009) · Food Chemistry · doi:10.1016/j.foodchem.2009.04.008 · Cited by 81
Effect of daily fruit ingestion on angiotensin converting enzyme activity, blood pressure, and oxidative stress in chronic smokers
McAnulty, S. R., McAnulty, L. S., Morrow, J. D., Khardouni, D., Shooter, L., Monk, J., Gross, S., & Brown, V. (2005) · Free Radical Research · doi:10.1080/10715760500306836 · Cited by 80
“shown to attenuate oxidative and inflammatory stress [12] and alleviate some of the detrimental effects associated with ROS production [13,14].”
Background

Authors: Youdim, K. A., McDonald, J., Kalt, W., & Joseph, J. A.
Affiliations: Tufts University (US)
Agriculture and Agri-Food Canada (CA)
Corresponding author: Youdim, Kuresh A.
ORCID: Youdim, Kuresh A.
Joseph, James A.
Venue: The Journal of Nutritional Biochemistry
Publisher: Elsevier BV
Published: 2002-05
Volume: 13
Issue: 5
Pages: 282-288
ISSN: 0955-2863 (ISSN-L)
DOI: 10.1016/s0955-2863(01)00221-2
OpenAlex: W1868361743
Cited by: 319
References: 40
Citations by year: 2026: 4 · 2025: 5 · 2024: 5 · 2023: 9 · 2022: 14 · 2021: 13 · 2020: 9 · 2019: 9 · 2018: 11 · 2017: 12 · 2016: 9 · 2015: 7 · 2014: 12 · 2013: 31 · 2012: 20
FWCI: 7.73
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: The Journal of Nutritional Biochemistry (publishedVersion)
PubMed (publishedVersion)
Funders: U.S. Department of Agriculture
Cranberry Institute
Topics: Health Sciences › Medicine › Biochemistry (medical) › Phytochemicals and Antioxidant Activities
Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
Health Sciences › Medicine › Biochemistry (medical) › Antioxidant Activity and Oxidative Stress
Keywords: dietary flavonoids, blueberry polyphenols, cranberry polyphenols, anthocyanins, hydroxycinnamic acids, microvascular endothelial cells, oxidative stress, TNF-α, inflammation, antioxidant activity, interleukin-8, MCP-1, ICAM-1, vascular disease

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