Cited by 158Genomics, phytochemicals, and oxidative stressPhytoestrogen effects and researchPhytochemicals and Antioxidant Activities

The DOI matches its Crossref record; 78 of the 78 references it cites were found in a registry or an index.

Targeting the redox sensitive Nrf2–Keap1 defense pathway in cardiovascular disease: protection afforded by dietary isoflavones

Mann, Giovanni E, Bonacasa, Barbara, Ishii, Tetsuro, Siow, Richard CM·2009·Current Opinion in Pharmacology

DOI 10.1016/j.coph.2008.12.012

Open this paper in CoChat — free account

Abstract

Cells have evolved highly regulated defense systems, including the redox sensitive Nrf2-Keap1 signaling pathway involved in the transcriptional activation of phase II defense and antioxidant genes in oxidative stress. Increased generation of reactive oxygen species (ROS) in cardiovascular disease (CVD) leads to impaired endothelial function and reduced nitric oxide (NO) bioavailability. Although epidemiological evidence suggests that diets containing plant-derived isoflavones (phytoestrogens) afford protection against CVDs, supplementation trials have largely reported only marginal health benefits. The molecular mechanisms by which soy isoflavones (genistein, daidzein, and equol) afford protection against oxidative stress in CVD remain to be investigated in large-scale clinical trials. Studies in animal models and cultured vascular cells have established that isoflavones increase eNOS activity and expression and activate the Nrf2-Keap1 signaling pathway, leading to an upregulation of detoxifying and antioxidant defense genes. We review recent advances in the understanding of the signal transduction pathways involved in the activation of endothelial NO production and Nrf2-Keap1-mediated antioxidant gene expression by dietary isoflavones.

Integrity signals

Registry

Crossref · 10.1016/j.coph.2008.12.012

Cites

78 of 78 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Free Radicals in the Physiological Control of Cell Function
Dröge, W. (2002) · Physiological Reviews · doi:10.1152/physrev.00018.2001 · Cited by 9,855
Effects of Conjugated Equine Estrogen in Postmenopausal Women With Hysterectomy: The Women's Health Initiative Randomized Controlled Trial
(2004) · JAMA · doi:10.1001/jama.291.14.1701 · Cited by 4,534
Comparison of the Ligand Binding Specificity and Transcript Tissue Distribution of Estrogen Receptors α and β
Kuiper, G. G. J. M., Carlsson, B., Grandien, K., Enmark, E., Häggblad, J., Nilsson, S., & Gustafsson, J.-A. (1997) · Endocrinology · doi:10.1210/endo.138.3.4979 · Cited by 4,442
Keap1 represses nuclear activation of antioxidant responsive elements by Nrf2 through binding to the amino-terminal Neh2 domain
Itoh, K., Wakabayashi, N., Katoh, Y., Ishii, T., Igarashi, K., Engel, J. D., & Yamamoto, M. (1999) · Genes & Development · doi:10.1101/gad.13.1.76 · Cited by 3,634
Self-citation
Mechanisms linking obesity with cardiovascular disease
Van Gaal, L. F., Mertens, I. L., & De Block, C. E. (2006) · Nature · doi:10.1038/nature05487 · Cited by 2,814
Role of Oxidative Modifications in Atherosclerosis
Stocker, R., & Keaney, J. F. (2004) · Physiological Reviews · doi:10.1152/physrev.00047.2003 · Cited by 2,651
Heme Oxygenase-1/Carbon Monoxide: From Basic Science to Therapeutic Applications
Ryter, S. W., Alam, J., & Choi, A. M. K. (2006) · Physiological Reviews · doi:10.1152/physrev.00011.2005 · Cited by 2,342
Flavonoids: antioxidants or signalling molecules?
Williams, R. J., Spencer, J. P. E., & Rice-Evans, C. (2004) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2004.01.001 · Cited by 2,016
Isolation of NF-E2-related factor 2 (Nrf2), a NF-E2-like basic leucine zipper transcriptional activator that binds to the tandem NF-E2/AP1 repeat of the beta-globin locus control region
Moi, P., Chan, K., Asunis, I., Cao, A., & Kan, Y. W. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.21.9926 · Cited by 1,607
Transcription Factor Nrf2 Coordinately Regulates a Group of Oxidative Stress-inducible Genes in Macrophages
Ishii, T., Itoh, K., Takahashi, S., Sato, H., Yanagawa, T., Katoh, Y., Bannai, S., & Yamamoto, M. P. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.21.16023 · Cited by 1,473
Self-citation

Flagged first, then by citations

Show all 78 references

Sorted by citations

Items 101–157 of 157

Developmental Conditioning of the Vasculature
Clough, G. F. (2014) · Comprehensive physiology · doi:10.1002/cphy.c140037 · Cited by 22
Flavonoids
Miranda, C. L., Maier, C. S., & Stevens, J. F. (2012) · Encyclopedia of Life Sciences · doi:10.1002/9780470015902.a0003068.pub2 · Cited by 17
Photoimmune protective effect of the phytoestrogenic isoflavonoid equol is partially due to its antioxidant activities
Widyarini, S., Domanski, D., Painter, N., & Reeve, V. E. (2012) · Photochemical & Photobiological Sciences · doi:10.1039/c2pp25022e · Cited by 16
Disturbed hemodynamics and oxidative stress interaction in endothelial dysfunction and AAA progression: Focus on Nrf2 pathway
Hasan, M. H., Al-Thani, H. A. S., El-Menyar, A. A., Zeidan, A., Thani, A. A. A., & Yalcin, H. C. (2023) · International Journal of Cardiology · doi:10.1016/j.ijcard.2023.131238 · Cited by 18
Polyphenols from Penthorum chinense Pursh. Attenuates high glucose-induced vascular inflammation through directly interacting with Keap1 protein
Sun, Y., He, L., Wang, W., Wang, T., Wan, H., Li, T., Wang, L., Gao, T., Chen, F., & Tang, L. (2020) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2020.113617 · Cited by 15
8-Hydroxydaidzein Downregulates JAK/STAT, MMP, Oxidative Phosphorylation, and PI3K/AKT Pathways in K562 Cells
Wu, P.-S., Wang, C., Chen, P.-S., Hung, J., Yen, J.-H., & Wu, M. (2021) · Biomedicines · doi:10.3390/biomedicines9121907 · Cited by 14
Concentration-dependent effects of the soy phytoestrogen genistein on the proteome of cultured cardiomyocytes
Sun, Z., Biela, L. M., Hamilton, K. L., & Reardon, K. F. (2012) · Journal of Proteomics · doi:10.1016/j.jprot.2012.04.001 · Cited by 13
Research protocol: effect of natural S-equol on blood pressure and vascular function- a six-month randomized controlled trial among equol non-producers of postmenopausal women with prehypertension or untreated stage 1 hypertension
Liu, Z.-M., Ho, S. C., Chen, Y., Xie, Y. J., Huang, Z.-G., & Ling, W. (2016) · BMC Complementary and Alternative Medicine · doi:10.1186/s12906-016-1065-5 · Cited by 13
Soy-Derived Equol Induces Antioxidant Activity in Zebrafish in an Nrf2-Independent Manner
Watanabe, A., Muraki, K., Tamaoki, J., & Kobayashi, M. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23095243 · Cited by 12
Effect of dehydroepiandrosterone treatment on hormone levels and antioxidant parameters in aged rats.
Yin, F.-J., Kang, J., Han, N., & Ma, H.-T. (2015) · Genetics and Molecular Research · doi:10.4238/2015.september.22.24 · Cited by 10
Theoretical studies on the antioxidant activity of potential marine xanthones
Thuy, P. T., & Ha, N. X. (2024) · Free Radical Research · doi:10.1080/10715762.2024.2438918 · Cited by 11
Dietary supplementation with mulberry leaf flavonoids and carnosic acid complex enhances the growth performance and antioxidant capacity via regulating the p38 MAPK/Nrf2 pathway
Liu, C., Huang, H., Chen, Y., Zhou, Y., Meng, T., Tan, B., He, W., Fu, X., & Xiao, D. (2024) · Frontiers in Nutrition · doi:10.3389/fnut.2024.1428577 · Cited by 11
Targets to Search for New Pharmacological Treatment in Idiopathic Parkinson’s Disease According to the Single-Neuron Degeneration Model
Huenchuguala, S., & Segura‐Aguilar, J. (2024) · Biomolecules · doi:10.3390/biom14060673 · Cited by 10
Cardiovascular Disease and Nutrition
Marhuenda, J., Villaño, D., Cerdá, B., & Zafrilla, M. P. (2019) · IntechOpen eBooks · doi:10.5772/intechopen.84370 · Cited by 10
Synthesis of Graphene Quantum Dot Magnesium Hydroxide Nanocomposites and Investigation of Their Antioxidant and Antimicrobial Activities
Kahraman, O., Turunç, E., Döğen, A., & Binzet, R. (2023) · Current Microbiology · doi:10.1007/s00284-023-03286-0 · Cited by 10
t-BHQ Protects Against Oxidative Damage and Maintains the Antioxidant Response in Malnourished Rats
Gavia-García, G., Rosas-Trejo, M. D. L. Á., García-Mendoza, E., Toledo-Pérez, R., Königsberg, M., Nájera-Medina, O., Luna‐López, A., & González-Torres, M. C. (2018) · Dose-Response · doi:10.1177/1559325818796304 · Cited by 9
Soy may help protect against cardiovascular disease
Cena, E. R., & Steinberg, F. M. (2011) · California Agriculture · doi:10.3733/ca.v065n03p118 · Cited by 8
Bioactive Nutraceuticals and Stroke
Alfieri, A., & Mann, G. E. (2014) · Elsevier eBooks · doi:10.1016/b978-0-12-411462-3.00037-0 · Cited by 8
Self-citation
Cysteine-based redox sensors in the cardiovascular system: from identification to physiology and drug discovery
Burgoyne, J. R., & Eaton, P. (2025) · Physiological Reviews · doi:10.1152/physrev.00051.2024 · Cited by 10
Autophagy characteristics of phytoestrogens in management and prevention of diseases: A narrative review of in-vivo and in-vitro studies
Khater, S. I., Shalabi, M., Alammash, B. B., Alrais, A. I., Al-Ahmadi, D. S., Alqahtani, L. S., Khamis, T., Abdelaziz, S., & Aldawy, K. (2023) · Journal of Advanced Veterinary and Animal Research · doi:10.5455/javar.2023.j683 · Cited by 6
Naturally Occurring Antioxidants
Ronzio, R. A. (2020) · Elsevier eBooks · doi:10.1016/b978-0-323-43044-9.00097-2 · Cited by 6
SH003 as a Redox-Immune Modulating Phytomedicine: A Ferroptosis Induction, Exosomal Crosstalk, and Translational Oncology Perspective
Park, M. N., Fahim, M. M. H., Kang, H. N., Bae, H., Rani, A. S., Nurkolis, F., Tallei, T. E., Ko, S., & Kim, B. (2025) · Cancers · doi:10.3390/cancers17213519 · Cited by 5
Isoflavone aglycones: Sources, bioavailability enhancement strategies, and health benefits
Sofyantoro, F., & Frediansyah, A. (2025) · Journal of Food Composition and Analysis · doi:10.1016/j.jfca.2025.108613 · Cited by 5
Coumestrol induces oxidative stress and impairs migration and embryonic growth
Wetendorf, M., Douglas, E. S., Goodwin, E. R., & Caron, K. M. (2023) · Reproduction · doi:10.1530/rep-23-0017 · Cited by 5
Saponins from Panax japonicas Reduces Myocardial Infarction Induced Reactive Oxygen Species Production and Cardiomyocyte Apoptosis via Activation of the Nrf-2 Pathway
Wei, N., Yuan, D., He, H. B., Xu, Y., Zhang, C. C., Wang, T., Liu, C. Q., & Liu, G. Y. (2014) · Advanced materials research · doi:10.4028/www.scientific.net/amr.881-883.339 · Cited by 5
Effect of nine diets on mRNAs of phase-II conjugation enzymes in livers of mice
Guo, Y., Cui, J. Y., Lü, H., & Klaassen, C. D. (2016) · Xenobiotica · doi:10.1080/00498254.2016.1213926 · Cited by 5
The effect of quercetin on endothelial cells is modified by heterocellular interactions
Tumova, S., Houghton, M. J., & Williamson, G. (2020) · Food & Function · doi:10.1039/d0fo00141d · Cited by 5
Modulation of Oxidative Stress in Cardiovascular Diseases
Jha, J. C., Bose, M., & Jandeleit-Dahm, K. A. M. (2019) · Springer eBooks · doi:10.1007/978-981-13-8946-7_10 · Cited by 5
S-Equol, an Antioxidant Metabolite of Soy Daidzein, and Oxidative Stress in Aging
Jackson, R. L., Greiwe, J. S., & Schwen, R. J. (2014) · Aging · doi:10.1016/b978-0-12-405933-7.00015-9 · Cited by 4
Maternal soy protein isolate diet during lactation programs deleterious effects on hepatic lipid metabolism, atherogenic indices, and function of adrenal in adult rat offspring
Ferreira, M. S., Luquetti, S. C. P. D., Brasiel, P. G. D. A., Mateus, K., Paulino, A. H. D. S., Carvalho, M. M. D. F., Andreazzi, A. E., & de Aguiar, A. S. (2021) · Journal of Developmental Origins of Health and Disease · doi:10.1017/s2040174421000180 · Cited by 4
Phytoestrogens Activate the Estrogen Receptor in HepG2 Cells
Kelly, L. A. (2015) · Methods in molecular biology · doi:10.1007/978-1-4939-3127-9_35 · Cited by 4
8-Hydroxydaidzein Induces Apoptosis and Inhibits AML-Associated Gene Expression in U-937 Cells: Potential Phytochemical for AML Treatment
Wu, P.-S., Wang, C., Hsu, H., Yen, J.-H., & Wu, M. (2023) · Biomolecules · doi:10.3390/biom13111575 · Cited by 3
Disease modifying effects of phytonutrients at gene levels
Manayi, A., Vazirian, M., & Hadjiakhoondi, A. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-815354-3.00005-8 · Cited by 3
Naturally Occurring Antioxidants
Ronzio, R. A. (2013) · Elsevier eBooks · doi:10.1016/b978-1-4377-2333-5.00108-5 · Cited by 3
Association of Soy Foods With Gastric Cancer Considering Helicobacter pylori: A Multi-Center Case-Control Study
Nam, S. Y., Jeon, S. W., Kwon, J. G., Chung, Y. J., Kwon, Y. H., Lee, S. H., Lee, J. Y., Yang, C., & Jo, J. (2024) · Journal of the Korean Gastric Cancer Association · doi:10.5230/jgc.2024.24.e39 · Cited by 2
Emerging druggable targets for cardiovascular disease
Curtis, M. J. (2009) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2009.02.001 · Cited by 2
Health Benefits and Pharmacological Molecular Properties of Isoflavandiol (Equol): In-silico and in-vitro Updates
Singh, P., Kushwaha, P. P., & Kumar, S. (2019) · Springer eBooks · doi:10.1007/978-981-13-6920-9_9 · Cited by 2
Developmental Origins of Endothelial Dysfunction: A Key Step in Cardiometabolic Disease
Torrens, C., Clough, G. F., & Hanson, M. A. (2011) · doi:10.1002/9781444347319.ch3 · Cited by 2
Quel rôle pour les polyphénols dans la protection cardiovasculaire
Morand, C. (2010) · Sciences des Aliments · doi:10.3166/sda.29.143-150 · Cited by 1
δ-Tocotrienol
Pilolli, F., Piroddi, M., Pierpaoli, E., Ciffolilli, S., Provinciali, M., & Galli, F. (2012) · CRC Press eBooks · doi:10.1201/b12502-10 · Cited by 1
Dietary Soy Impact on Host Transcriptome Profile—A Review
Anghel, A., Sala-Cîrtog, M., Marian, C., Samoilă, C., & Sîrbu, I. O. (2021) · Applied Sciences · doi:10.3390/app11177905 · Cited by 1
Polyphenols
(2016) · Contemporary food engineering · doi:10.1201/9781315371245-2 · Cited by 1
Cardiovascular D isease and N u tritio n
Wildman, R. E. C., & Medeiros, D. M. (2014) · CRC Press eBooks · doi:10.1201/b16554-20 · Cited by 1
PROTECTION AGAINST ENDOTHELIAL INFLAMMATION BY GREEN TEA FLAVONOIDS
Zheng, Y. (2010) · UKnowledge (University of Kentucky)
POLYCHLORINATED BIPHENYL-INDUCED ENDOTHELIAL CELL DYSFUNCTION AND ITS MODULATION BY DIETARY LIPIDS
Májková, Z. (2010) · UKnowledge (University of Kentucky)
La voie Nrf2 en pathologie
Boutten, A., Goven, D., Artaud-Macari, É., & Bonay, M. (2011)
Potentiation of Cellular Defense Capacity by Phytochemicals Activating NF-E2-Related Factor 2 for the Prevention and/or Treatment of Alzheimer’s Disease
Park, G. H., & Jang, J. (2015) · Springer eBooks · doi:10.1007/978-4-431-55763-0_21
Pro-oxidant Nrf2 inducers: Promiscuity and protection
Farrell‐Dillon, K., & Fraser, P. A. (2016) · Vascular Pharmacology · doi:10.1016/j.vph.2016.10.007
Effects of Oxidative Stress on the Expression and Function of Inducible Nitric Oxide Synthase in Cultured Vascular Smooth Muscle Cells
Bingi, P. K. (2017) · University of Hertfordshire Research Archive (University of Hertfordshire) · doi:10.18745/th.17660
Extratos biotransformados de fenólicos de cítricos e atividade anti-inflamatória "in vitro"
Moala, T. (2016) · doi:10.47749/t/unicamp.2016.971023
Reactive Oxygen Species in the Pathogenesis of Chronic Kidney Disease: Lessons Derived from Diabetic Nephropathy
Kashihara, N., Satoh, M., & Kanwar, Y. S. (2014) · Springer eBooks · doi:10.1007/978-3-642-30018-9_185
Methylglyoxal, the glyoxalase pathway and advanced glycation endproducts in type 2 diabetes and cardiovascular disease
Hanssen, N. M. J. (2015) · doi:10.26481/dis.20150520nh
Fatty liver disease
van de Wier, B. (2016) · Research Publications (Maastricht University) · doi:10.26481/dis.20160705bw
Multi-functional Ligands and Molecular Hybridization: Conceptual Aspects and Application in the Innovative Design of Drug Candidate Prototypes for Neurodegenerative Diseases
Silva, M. D. F., Viegas, F. P. D., Gontijo, V. S., Ortiz, C. J. C., Franco, G. D. R. R., Ernesto, J. T., Damásio, C. M., Fonseca, G. P. D. S., Silva, I. M. F., Massuda, L. E., et al. (2023) · Frontiers in clinical drug research. CNS and neurological disorders · doi:10.2174/9789815123319123110003
Impact des flavanones des agrumes sur la prévention de l'athérosclérose et mécanismes d'action mis en jeu
Chanet, A. (2011) · theses.fr (ABES) · doi:10.70675/c9b0983czed0bz4b1dzb975z2866bc9e5763
Astaxanthin as a regulator of Nrf2, NF-κB, and their interactions: Molecular mechanisms and potential clinical applications
Frumento, D., & Ţălu, Ş. (2026) · Journal of Cellular Biotechnology · doi:10.1177/23523689261467604
Active-Component-Based Multi-Target Repair: Advances in the Mechanisms by Which Six Natural Oils and Soy Isoflavones Improve Skin Barrier Function during Menopause
白, 新. (2026) · Advances in Clinical Medicine · doi:10.12677/acm.2026.1672740

Authors: Mann, G. E., Bonacasa, B., Ishii, T., & Siow, R. C.
Affiliations: King's College London (GB)
University of Tsukuba (JP)
Corresponding author: Mann, Giovanni E
ORCID: Mann, Giovanni E
Siow, Richard CM
Venue: Current Opinion in Pharmacology
Publisher: Elsevier BV
Published: 2009-04
Volume: 9
Issue: 2
Pages: 139-145
ISSN: 1471-4892 (ISSN-L)
DOI: 10.1016/j.coph.2008.12.012
OpenAlex: W2030386807
Cited by: 158
References: 78
Citations by year: 2026: 2 · 2025: 3 · 2024: 5 · 2023: 8 · 2022: 3 · 2021: 7 · 2020: 9 · 2019: 8 · 2018: 5 · 2017: 6 · 2016: 18 · 2015: 13 · 2014: 11 · 2013: 8 · 2012: 11
FWCI: 1.33
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Current Opinion in Pharmacology (publishedVersion)
PubMed (publishedVersion)
Research Portal (King's College London) (submittedVersion)
Funders: British Heart Foundation (FS/07/020, PG/07/006/22212)
Heart Research UK
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics, phytochemicals, and oxidative stress
Health Sciences › Nursing › Nutrition and Dietetics › Phytoestrogen effects and research
Health Sciences › Medicine › Biochemistry (medical) › Phytochemicals and Antioxidant Activities
Keywords: Nrf2/Keap1 pathway, isoflavones, soy isoflavones, genistein, daidzein, equol, phytoestrogens, cardiovascular disease, oxidative stress, reactive oxygen species, endothelial nitric oxide synthase, nitric oxide bioavailability, endothelial function, antioxidant gene expression, dietary supplementation
MeSH terms: Kelch-Like ECH-Associated Protein 1, Animals, Antioxidants, Cardiovascular Diseases, Clinical Trials as Topic, Endothelium, Vascular, Humans, Isoflavones, Models, Biological, Signal Transduction, Drug Delivery Systems, Oxidants, Reactive Oxygen Species, Nitric Oxide Synthase, Soy Foods, Intracellular Signaling Peptides and Proteins, NF-E2-Related Factor 2

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Targeting the redox sensitive Nrf2–Keap1 defense pathway in cardiovascular disease: protection afforded by dietary isoflavones

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Citations

Cites

Cited by

Related

Metadata

Record

About these checks