Trial reportPloS one2013
Estrogen receptor and PI3K/Akt signaling pathway involvement in S-(-)equol-induced activation of Nrf2/ARE in endothelial cells.
Trial report in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
42 citing papers in PubMed, 1 synthesis or guideline pooled it, 80 citations in OpenAlex.
- Mapping the evolution of botanical interventions for diabetic neuropathy: a two-database bibliometric landscape from 2005 to mid-2025.Frontiers in nutrition · 2025Pooled it
- Estrogen receptors and the NRF2 pathway: bridging hormonal regulation and stress response in the gut.Frontiers in endocrinology · 2026Review
- Review
- Polyphenol-Derived Microbiota Metabolites and Cardiovascular Health: A Concise Review of Human Studies.Antioxidants (Basel, Switzerland) · 2024Review
- Effect of the Mediterranean Diet (MeDi) on the Progression of Retinal Disease: A Narrative Review.Nutrients · 2024Review
- Nongenomic ERα-AMPK Signaling Regulates Sex-Dependent Bcrp Transport Activity at the Blood-Brain Barrier.Endocrinology · 2024Article
- Inhibiting Caveolin-1-Related Akt/mTOR Signaling Pathway Protects Against N-methyl-D-Aspartate Receptor Activation-Mediated Dysfunction of Blood-Brain Barrier in vitro.Molecular neurobiology · 2024Article
- The relationship between equol production status and normal tension glaucoma.International ophthalmology · 2024Article
- Polyphenols mediated attenuation of diabetes associated cardiovascular complications: A comprehensive review.Journal of diabetes and metabolic disorders · 2024Review
- An insight into role of amino acids as antioxidants via NRF2 activation.Amino acids · 2024Review
- Isoflavones Effects on Vascular and Endothelial Outcomes: How Is the Gut Microbiota Involved?Pharmaceuticals (Basel, Switzerland) · 2024Review
- The cardiovascular toxicity of polystyrene microplastics in rats: based on untargeted metabolomics analysis.Frontiers in pharmacology · 2024Article
- Article
- The role of phosphoinositide 3-kinases in immune-inflammatory responses: potential therapeutic targets for abdominal aortic aneurysm.Cell cycle (Georgetown, Tex.) · 2022Review
- Potential Protective Mechanisms of S-equol, a Metabolite of Soy Isoflavone by the Gut Microbiome, on Cognitive Decline and Dementia.International journal of molecular sciences · 2022Review
- Role of Nuclear Factor Erythroid 2 (Nrf2) in the Recovery of Long COVID-19 Using Natural Antioxidants: A Systematic Review.Antioxidants (Basel, Switzerland) · 2022Review
- Soy-Derived Equol Induces Antioxidant Activity in Zebrafish in an Nrf2-Independent Manner.International journal of molecular sciences · 2022Article
- Potential Protective Effects of Equol (Soy Isoflavone Metabolite) on Coronary Heart Diseases-From Molecular Mechanisms to Studies in Humans.Nutrients · 2021Review
- Phytoestrogens (Resveratrol and Equol) for Estrogen-Deficient Skin-Controversies/Misinformation versus Anti-Aging In Vitro and Clinical Evidence via Nutraceutical-Cosmetics.International journal of molecular sciences · 2021Review
- [Effects and mechanism of estrogen receptor β agonist on the migration and oxidative stress of human umbilical vein endothelial cell under high glucose condition].Zhonghua shao shang za zhi = Zhonghua shaoshang zazhi = Chinese journal of burns · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
S-(-)equol, a natural product of the isoflavone daidzein, has been reported to offer cytoprotective effects with respect to the cardiovascular system, but how this occurs is unclear. Interestingly, S-(-)equol is produced by the human gut, suggesting a role in physiological processes. We report that treatment of human umbilical vein endothelial cells and EA.hy926 cells with S-(-)equol induces ARE-luciferase reporter gene activity that is dose and time dependent. S-(-)equol (10-250 nM) increases nuclear factor-erythroid 2-related factor 2 (Nrf2) as well as gene products of Nrf2 target genes heme oxygenase-1 (HO-1) and NAD(P)H (nicotinamide-adenine-dinucleotide-phosphate) quinone oxidoreductase 1 (NQO1). Endothelial cells transfected with an HA-Nrf2 expression plasmid had elevated HA-Nrf2, HO-1, and NQO1 in response to S-(-)equol exposure. S-(-)equol treatment affected Nrf2 mRNA only slightly but significantly increased HO-1 and NQO1 mRNA. The pretreatment of cells with specific ER inhibitors or PI3K/Akt (ICI182,780 and LY294002) increased Nrf2, HO-1, and NQO1 protein, impaired nuclear translocation of HA-Nrf2, and decreased ARE-luciferase activity. Identical experiments were conducted with daidzein, which had effects similar to S-(-)equol. In addition, DPN treatment (an ERβ agonist) induced the ARE-luciferase reporter gene, promoting Nrf2 nuclear translocation. Cell pretreatment with an ERβ antagonist (PHTPP) impaired S-(-)equol-induced Nrf2 activation. Pre-incubation of cells followed by co-treatment with S-(-)equol significantly improved cell survival in response to H2O2 or tBHP and reduced apoptotic and TUNEL-positively-stained cells. Notably, the ability of S-(-)equol to protect against H2O2-induced cell apoptosis was attenuated in cells transfected with an siRNA against Nrf2. Thus, beneficial effects of S-(-)equol with respect to cytoprotective antioxidant gene activation may represent a novel strategy to prevent and treat cardiovascular diseases.
Indexed as
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.