ArticleProceedings of the National Academy of Sciences of the United States of America1999
The antioxidant neuroprotective effects of estrogens and phenolic compounds are independent from their estrogenic properties.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 124 papers, 1 of them a synthesis that pooled it.
What it found
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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
124 citing papers in PubMed, 1 synthesis or guideline pooled it, 409 citations in OpenAlex.
- Premature and early menopause and neuroimaging biomarkers of neurodegenerative diseases: a systematic review.Frontiers in dementia · 2026Pooled it
- Sex differences in ferroptosis-related vulnerability to autism-like deficits in the adolescent medial prefrontal cortex following embryonic valproic acid exposure.Biology of sex differences · 2026Article
- Aluminium as a Metalloestrogen: Toxicological Pathways, Endocrine Disruption and Systemic Health Implications.Maedica · 2026Review
- Retinal and choroidal changes in diabetic patients before definitive diagnosis of diabetic retinopathy: a two-year prospective study.Journal of endocrinological investigation · 2026Article
- 24-Hour Ultra-Marathon Running: A Narrative Review of Performance Factors and Physiological Impacts.Sports medicine - open · 2026Review
- The estrogen-ferroptosis axis in postmenopausal osteoporosis, osteoarthritis, and intervertebral disc degeneration: shared mechanisms and emerging evidence.Frontiers in immunology · 2026Review
- Frozen Shoulder as a Systemic Immunometabolic Disorder: The Roles of Estrogen, Thyroid Dysfunction, Endothelial Health, Lifestyle, and Clinical Implications.Journal of clinical medicine · 2025Review
- The role of hydroxyindoles in protecting neuronal cultures from ferroptosis.Cell death discovery · 2025Article
- An Update of Fungal Endophyte Diversity and Strategies for Augmenting Therapeutic Potential of their Potent Metabolites: Recent Advancement.Applied biochemistry and biotechnology · 2025Review
- Raloxifene Prevents Chemically-Induced Ferroptotic Neuronal Death In Vitro and In Vivo.Molecular neurobiology · 2025Article
- Cannabinoids: Role in Neurological Diseases and Psychiatric Disorders.International journal of molecular sciences · 2024Review
- Article
- Mechanisms of Estrogen Influence on Skeletal Muscle: Mass, Regeneration, and Mitochondrial Function.Sports medicine (Auckland, N.Z.) · 2022Review
- The Role of Lipid Rafts and Membrane Androgen Receptors in Androgen's Neurotoxic Effects.Journal of the Endocrine Society · 2022Article
- Catalase, a therapeutic target in the reversal of estrogen-mediated aging.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Article
- Oleuropein Improves Cognitive Dysfunction and Neuroinflammation in Diabetic Rats through the PI3K/Akt/mTOR Pathway.Applied bionics and biomechanics · 2022Article
- Valorizing the usage of olive leaves, bioactive compounds, biological activities, and food applications: A comprehensive review.Frontiers in nutrition · 2022Review
- Neurodegenerative Disease: Roles for Sex, Hormones, and Oxidative Stress.Endocrinology · 2021Review
- Estrogens and the regulation of glucose metabolism.World journal of diabetes · 2021Review
- In Vitro Studies on Therapeutic Effects of Cannabidiol in Neural Cells: Neurons, Glia, and Neural Stem Cells.Molecules (Basel, Switzerland) · 2021Review
64 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Among the family of steroidal molecules, only estrogens have the capability of preventing neuronal cell death caused by increased oxidative burden. Employing neuronal cell lines, brain membrane, and low density lipoprotein oxidation assays, we show that the antioxidant and neuroprotective effects of estrogens are dependent not on their genomic properties as hormones but rather on their basic chemical properties as hydrophobic phenolic molecules. Concentrations of 17beta-estradiol of 0.1-500 nM, which confer maximum estrogen receptor-dependent gene transcription in vitro as well as maximum estrogen receptor binding, respectively, do not show antioxidant or neuroprotective effects. In contrast, phenolic compounds such as 2,4,6-trimethylphenol, N-acetylserotonin, and 5-hydroxyindole exhibit neuroprotective effects without any estrogenicity. Comparing various natural and synthetic mono- and polyphenolic compounds, no correlation between their antioxidant cytoprotective effect and their estrogenic potency can be seen. These results call into question the idea of a general correlation between the intended pharmacological effects of estrogens and phenolic compounds and their effect on estrogen receptor-dependent pathways. Furthermore, they may open the door toward the rational design of neuroprotective antioxidants with decreased hormonal side effects.
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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.