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

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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

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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.

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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

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

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