Estrogen receptor-independent inhibition of tumor necrosis factor-α gene expression by phytoestrogen equol is mediated by blocking nuclear factor-κB activation in mouse macrophages
Abstract
Equol has been suggested to possess protective effects on bone. However, the underlying mechanism of osteoprotective effect of equol has not been fully understood. In the present study, we examined the effect of equol on tumor necrosis factor-alpha (TNF-alpha) gene expression to elucidate a possible mechanism by which equol exerts osteoprotective effect. In vivo administration of equol inhibited TNF-alpha production by peritoneal macrophages isolated from LPS-treated mice. Equol also dose-dependently inhibited TNF-alpha production and TNF-alpha mRNA expression in LPS-stimulated mouse macrophages. Pretreatment of cells with ICI 182.780, an estrogen receptor antagonist, had no effect on the inhibitory efficacy of equol on LPS-induced TNF-alpha production. Further study demonstrated that equol inhibited NF-kappaB DNA binding and NF-kappaB-dependent reporter gene expression in activated RAW 264.7 cells. Moreover, equol blocked degradation of IkappaBalpha and IkappaBbeta and nuclear translocation of p65 subunit of NF-kappaB in activated RAW 264.7 cells. These results suggest that the inhibitory effect of equol on TNF-alpha expression is mediated, at least in part, by blocking NF-kappaB activation and the inhibition of TNF-alpha expression by equol might be involved in its osteoprotective effect.
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Equol inhibits NF-KB in macrophages and blocks production of free radicals like nitric oxide (NO).
“Equol has been shown to inhibit NF-KB in macrophages and block the production of free radicals like nitric oxide (NO) [106,107].”
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- Authors
- Kang, J. S., Yoon, Y. D., Han, M. H., Han, S.-B., Lee, K., Kang, M. R., Moon, E.-Y., Jeon, Y. J., Park, S.-K., & Kim, H. M.
- Affiliations
- Korea Research Institute of Bioscience and Biotechnology (KR)
- Chosun University (KR)
- Corresponding author
- Park, Song-Kyu
- Kim, Hwan Mook
- Venue
- Biochemical Pharmacology
- Publisher
- Elsevier BV
- Published
- 2005-12
- Volume
- 71
- Issue
- 1-2
- Pages
- 136-143
- ISSN
- 0006-2952 (ISSN-L)
- OpenAlex
- W2032853997
- Cited by
- 43
- References
- 53
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 4 · 2023: 2 · 2022: 2 · 2021: 1 · 2020: 1 · 2019: 3 · 2018: 1 · 2017: 1 · 2016: 4 · 2014: 1 · 2012: 3
- FWCI
- 2.67
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biochemical Pharmacology (publishedVersion)
- PubMed (publishedVersion)
- KRIBB Repository (submittedVersion)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Phytoestrogen effects and research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Health Sciences › Medicine › Complementary and alternative medicine › Natural Compounds in Disease Treatment
- Keywords
- equol, phytoestrogens, TNF-α, NF-κB activation, estrogen receptor-independent mechanism, macrophages, osteoprotection, IκBα degradation, p65 nuclear translocation, RAW 264.7 macrophages, LPS-stimulated inflammation, fulvestrant
- MeSH terms
- Animals, Base Sequence, Cell Line, Enzyme-Linked Immunosorbent Assay, Gene Expression Regulation, Isoflavones, Macrophages, Receptors, Estrogen, Transcription, Genetic, Tumor Necrosis Factor-alpha, NF-kappa B, DNA Primers, Reverse Transcriptase Polymerase Chain Reaction, Protein Transport, Electrophoretic Mobility Shift Assay, Mice, Equol
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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