ArticleFree radical biology & medicine2015
Phytoestrogens modulate hepcidin expression by Nrf2: Implications for dietary control of iron absorption.
Article in Free radical biology & medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 47 citations in OpenAlex.
- Trace Element and Phytochemical Characterization of Pinus pinaster and Pinus halepensis Bark Extracts with Protective Effects Against Phenylhydrazine-induced Hemolytic Anemia in Rats.Biological trace element research · 2026Article
- Iron Deficiency and Iron Deficiency Anemia: A Comprehensive Overview of Established and Emerging Concepts.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Signaling pathways and targeted therapy for pulmonary hypertension.Signal transduction and targeted therapy · 2025Review
- Thirty years of NRF2: advances and therapeutic challenges.Nature reviews. Drug discovery · 2025Review
- Flavonoid-Phenolic Acid Hybrids Are Potent Inhibitors of Ferroptosis via Attenuation of Mitochondrial Impairment.Antioxidants (Basel, Switzerland) · 2023Article
- Article
- Dimethyl Fumarate and Intestine: From Main Suspect to Potential Ally against Gut Disorders.International journal of molecular sciences · 2023Review
- Regulation of Host Defense Peptide Synthesis by Polyphenols.Antibiotics (Basel, Switzerland) · 2023Review
- Review
- Melatonin Regulates Iron Homeostasis by Inducing Hepcidin Expression in Hepatocytes.International journal of molecular sciences · 2022Article
- Investigating the Molecular Mechanisms of Renal Hepcidin Induction and Protection upon Hemoglobin-Induced Acute Kidney Injury.International journal of molecular sciences · 2022Article
- The Role of Oxidative Stress in the Pathogenesis of Vitiligo: A Culprit for Melanocyte Death.Oxidative medicine and cellular longevity · 2022Review
- RNAseq analysis of treatment-dependent signaling changes during inflammation in a mouse cutaneous wound healing model.BMC genomics · 2021Article
- Epigallocatechin-3-Gallate Suppresses BMP-6-Mediated SMAD1/5/8 Transactivation of Hepcidin Gene by Inducing SMILE in Hepatocytes.Antioxidants (Basel, Switzerland) · 2021Article
- Nrf2 activation does not affect adenoma development in a mouse model of colorectal cancer.Communications biology · 2021Article
- A disease-causing mutation K240E disrupts ferroportin trafficking by SUMO (ferroportin SUMOylation).Biochemistry and biophysics reports · 2021Article
- Natural Antioxidants in Anemia Treatment.International journal of molecular sciences · 2021Review
- Effects of tocotrienol supplementation in Friedreich's ataxia: A model of oxidative stress pathology.Experimental biology and medicine (Maywood, N.J.) · 2020Article
- Therapeutic Advances in Regulating the Hepcidin/Ferroportin Axis.Pharmaceuticals (Basel, Switzerland) · 2019Review
- Role of Dietary Flavonoids in Iron Homeostasis.Pharmaceuticals (Basel, Switzerland) · 2019Review
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Authors and funding
3 authors at 2 institutions in 1 country.
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Abstract
Hepcidin is a liver-derived antimicrobial peptide that regulates iron absorption and is also an integral part of the acute phase response. In a previous report, we found evidence that this peptide could also be induced by toxic heavy metals and xenobiotics, thus broadening its teleological role as a defensin. However it remained unclear how its sensing of disparate biotic and abiotic stressors might be integrated at the transcriptional level. We hypothesized that its function in cytoprotection may be regulated by NFE2-related factor 2 (Nrf2), the master transcriptional controller of cellular stress defenses. In this report, we show that hepcidin regulation is inextricably linked to the acute stress response through Nrf2 signaling. Nrf2 regulates hepcidin expression from a prototypical antioxidant response element in its promoter, and by synergizing with other basic leucine-zipper transcription factors. We also show that polyphenolic small molecules or phytoestrogens commonly found in fruits and vegetables including the red wine constituent resveratrol can induce hepcidin expression in vitro and post-prandially, with concomitant reductions in circulating iron levels and transferrin saturation by one such polyphenol quercetin. Furthermore, these molecules derepress hepcidin promoter activity when its transcription by Nrf2 is repressed by Keap1. Taken together, the data show that hepcidin is a prototypical antioxidant response or cytoprotective gene within the Nrf2 transcriptional circuitry. The ability of phytoestrogens to modulate hepcidin expression in vivo suggests a novel mechanism by which diet may impact iron homeostasis.
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