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

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

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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Crossref · 10.1016/j.coph.2008.12.012

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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
Venue
Current Opinion in Pharmacology
Publisher
Elsevier BV
Published
2009-04
Volume
9
Issue
2
Pages
139-145
ISSN
1471-4892 (ISSN-L)
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
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 › Medicine › Pathology and Forensic Medicine › Phytoestrogen effects and research
  • Health Sciences › Medicine › Biochemistry › 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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