Equol inhibits nitric oxide production and inducible nitric oxide synthase gene expression through down-regulating the activation of Akt

Kang, Jong Soon; Yoon, Yeo Dae; Han, Mi Hwa; Han, Sang-Bae; Lee, Kiho; Park, Song-Kyu; Kim, Hwan Mook

doi:10.1016/j.intimp.2006.12.004

Cited by 45Phytoestrogen effects and researchNatural Compounds in Disease TreatmentInflammatory mediators and NSAID effects

Equol inhibits nitric oxide production and inducible nitric oxide synthase gene expression through down-regulating the activation of Akt

Kang, Jong Soon, Yoon, Yeo Dae, Han, Mi Hwa, Han, Sang-Bae, Lee, Kiho, Park, Song-Kyu, Kim, Hwan Mook·2007·International Immunopharmacology

DOI 10.1016/j.intimp.2006.12.004

Open this paper in CoChat — free account

Abstract

In the present study, we report the inhibitory effect of equol on nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) gene expression in murine macrophages. In vivo administration of equol (i.p.) attenuated NO production by peritoneal adherent cells isolated from lipopolysaccharide (LPS)-treated mice. Equol dose-dependently inhibited the LPS-induced production of NO in isolated peritoneal adherent cells and RAW 264.7 cells. The mRNA expression of iNOS was also blocked by equol in LPS-stimulated RAW 264.7 cells. Further study demonstrated that the LPS-induced activation of Akt was suppressed by equol in RAW 264.7 cells while the activation of ERK, SAPK/JNK and p38 MAP kinase was not affected. Equol also blocked LPS-induced NF-kappaB activation. Moreover, the LPS-induced NO production and NF-kappaB activation was inhibited by LY294002, a specific inhibitor of phosphatidylinositol 3-kinase/Akt pathway, in RAW 264.7 cells. These results suggest that equol might inhibit NO production and iNOS gene expression, at least in part, by blocking Akt activation and subsequent down-regulation of NF-kappaB activity.

Integrity signals

Registry

Crossref · 10.1016/j.intimp.2006.12.004

Cites

44 of 44 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

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].”
From Equol’s Anti-Aging Effects Protect against Environmental Assaults by Increasing Skin Antioxidant Defense and ECM Proteins While Decreasing Oxidative Stress and Inflammation (2018) · cites this paper as [107]

Nitric oxide as a secretory product of mammalian cells
Nathan, C. (1992) · The FASEB Journal · doi:10.1096/fasebj.6.12.1381691 · Cited by 4,350 · see citing works
Atherosclerosis
Glass, C. K., & Witztum, J. L. (2001) · Cell · doi:10.1016/s0092-8674(01)00238-0 · Cited by 3,049 · see citing works
Role of transcription factor NF-kappa B/Rel in induction of nitric oxide synthase.
Xie, Q. W., Kashiwabara, Y., & Nathan, C. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)37600-7 · Cited by 2,212 · see citing works
L-arginine is the physiological precursor for the formation of nitric oxide in endothelium-dependent relaxation
Palmer, R. M. J., Rees, D. D., Ashton, D. S., & Moncada, S. (1988) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(88)81362-7 · Cited by 1,348 · see citing works
Promoter of the mouse gene encoding calcium-independent nitric oxide synthase confers inducibility by interferon gamma and bacterial lipopolysaccharide.
Xie, Q. W., Whisnant, R., & Nathan, C. F. (1993) · The Journal of Experimental Medicine · doi:10.1084/jem.177.6.1779 · Cited by 1,118 · see citing works
Soy protein and isoflavones: their effects on blood lipids and bone density in postmenopausal women
Potter, S. M., Baum, J. A., Teng, H., Stillman, R. J., Shay, N. F., & Erdman, J. W. (1998) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/68.6.1375s · Cited by 862 · see citing works
Akt Stimulates the Transactivation Potential of the RelA/p65 Subunit of NF-κB through Utilization of the IκB Kinase and Activation of the Mitogen-activated Protein Kinase p38
Madrid, L. V., Mayo, M. W., Reuther, J. Y., & Baldwin, A. S. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m101103200 · Cited by 777 · see citing works
Dietary effects on breast-cancer risk in Singapore
Lee, H. P., Lee, J. W. N., Gourley, L., Duffy, S. W., Day, N., & Estève, J. (1991) · The Lancet · doi:10.1016/0140-6736(91)92867-2 · Cited by 765 · see citing works
Case-control study of phyto-oestrogens and breast cancer
Ingram, D., Sanders, K., Kolybaba, M. L., & Lopez, D. G. (1997) · The Lancet · doi:10.1016/s0140-6736(97)01339-1 · Cited by 722 · see citing works
Interaction of Phytoestrogens with Estrogen Receptors .ALPHA. and .BETA..
Morito, K., HIROSE, T., Kinjo, J., Hirakawa, T., Okawa, M., Nohara, T., Ogawa, S., Inoue, S., Muramatsu, M., & Masamune, Y. (2001) · Biological and Pharmaceutical Bulletin · doi:10.1248/bpb.24.351 · Cited by 615 · see citing works
Differential regulation of IκB kinase α and β by two upstream kinases, NF-κB-inducing kinase and mitogen-activated protein kinase/ERK kinase kinase-1
Nakano, H., Shindo, M., Komazawa‐Sakon, S., Nishinaka, S., Mihara, M., Yagita∥, H., & Okumura, K. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.7.3537 · Cited by 518 · see citing works
Interaction of Phytoestrogens with Estrogen Receptors .ALPHA. and .BETA.(II).
Morito, K., Aomori, T., Hirose, T., Kinjo, J., Hasegawa, J., Ogawa, S., Inoue, S., Muramatsu, M., & Masamune, Y. (2002) · Biological and Pharmaceutical Bulletin · doi:10.1248/bpb.25.48 · Cited by 464 · see citing works
Antioxidant Activity of Phytoestrogenic Isoflavones
Ruiz‐Larrea, M. B., Mohan, A. R., Paganga, G., Miller, N. J., Bolwell, G. P., & Rice-Evans, C. A. (1997) · Free Radical Research · doi:10.3109/10715769709097785 · Cited by 463 · see citing works
Antioxidant Activities of Isoflavones and Their Biological Metabolites in a Liposomal System
Arora, A., Nair, M. G., & Strasburg, G. M. (1998) · Archives of Biochemistry and Biophysics · doi:10.1006/abbi.1998.0783 · Cited by 404 · see citing works
Distinct Roles of the IκB Kinase α and β Subunits in Liberating Nuclear Factor κB (NF-κB) from IκB and in Phosphorylating the p65 Subunit of NF-κB
Sizemore, N., Lerner, N., Dombrowski, N., Sakurai, H., & Stark, G. R. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m110572200 · Cited by 391 · see citing works
Antioxidant Efficacy of Phytoestrogens in Chemical and Biological Model Systems
Mitchell, J. H., Gardner, P. T., McPhail, D. B., Morrice, P. C., Collins, A. R., & Duthie, G. G. (1998) · Archives of Biochemistry and Biophysics · doi:10.1006/abbi.1998.0951 · Cited by 322 · see citing works
Phosphatidylinositol 3‐kinase is involved in Toll‐like receptor 4‐mediated cytokine expression in mouse macrophages
Ojaniemi, M., Glumoff, V., Harju, K., Vähä-Mäkilä, M., Vuori, K., & Hallman, M. (2003) · European Journal of Immunology · doi:10.1002/eji.200323376 · Cited by 321 · see citing works
NO, nitrotyrosine, and cyclic GMP in signal transduction.
Hanafy, K. A., Krumenacker, J. S., & Murad, F. (2001) · PubMed · Cited by 236 · see citing works
Genistein, the Dietary-Derived Angiogenesis Inhibitor, Prevents LDL Oxidation and Protects Endothelial Cells From Damage by Atherogenic LDL
Kapiotis, S., Hermann, M., Held, I., et al. (1997) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.17.11.2868 · Cited by 234 · see citing works
Diet and Its Preventive Role in Prostatic Disease
Denis, L., Morton, M. S., & Griffiths, K. (1999) · European Urology · doi:10.1159/000019912 · Cited by 223 · see citing works
Substitution of Chloroform by Bromochloropropane in the Single-Step Method of RNA Isolation
Chomczyński, P., & Mackey, K. (1995) · Analytical Biochemistry · doi:10.1006/abio.1995.1126 · Cited by 216 · see citing works
Deficiency in Inducible Nitric Oxide Synthase Results in Reduced Atherosclerosis in Apolipoprotein E-Deficient Mice
Detmers, P. A., Hernandez, M., Mudgett, J. S., Hassing, H., Burton, C. A., Mundt, S. S., Chun, S. H., Fletcher, D. S., Card, D., Lisnock, J., et al. (2000) · The Journal of Immunology · doi:10.4049/jimmunol.165.6.3430 · Cited by 206 · see citing works
Macrophage activation by polysaccharide isolated from Astragalus membranaceus
Lee, K. Y., & Jeon, Y. J. (2005) · International Immunopharmacology · doi:10.1016/j.intimp.2005.02.020 · Cited by 163 · see citing works
Self-citation
Serum phytoestrogens and prostate cancer risk in a nested case‐control study among Japanese men
Ozasa, K., Nakao, M., Watanabe, Y., Hayashi, K., Miki, T., Mikami, K., Mori, M., Sakauchi, F., Washio, M., Ito, Y., et al. (2004) · Cancer Science · doi:10.1111/j.1349-7006.2004.tb03172.x · Cited by 163 · see citing works
Isoflavone Aglycone–Rich Extract without Soy Protein Attenuates Atherosclerosis Development in Cholesterol-Fed Rabbits
Yamakoshi, J., Izumi, T., Tobe, K., Saito, M., Kataoka, S., Obata, A., Kikuchi, M., & Piskuła, M. K. (2000) · Journal of Nutrition · doi:10.1093/jn/130.8.1887 · Cited by 150 · see citing works
Intake of 25 g of Soybean Protein with or without Soybean Fiber Alters Plasma Lipids in Men with Elevated Cholesterol Concentrations
Bakhit, R. M., Klein, B. P., Essex-Sorlie, D., Ham, J. O., Erdman, J. W., & Potter, S. M. (1994) · Journal of Nutrition · doi:10.1093/jn/124.2.213 · Cited by 143 · see citing works
Soybean isoflavonoids and their metabolic products inhibit in vitro lipoprotein oxidation in serum
Hodgson, J. M., Croft, K. D., Puddey, I. B., Mori, T. A., & Beilin, L. J. (1996) · The Journal of Nutritional Biochemistry · doi:10.1016/s0955-2863(96)00133-7 · Cited by 140 · see citing works
The phytoestrogen equol increases nitric oxide availability by inhibiting superoxide production: an antioxidant mechanism for cell-mediated LDL modification
Hwang, J., Wang, J., Morazzoni, P., Hodis, H. N., & Sevanian, A. (2003) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(03)00104-7 · Cited by 137 · see citing works
The therapeutic potential of phytoestrogens
Wiseman, H. (2000) · Expert Opinion on Investigational Drugs · doi:10.1517/13543784.9.8.1829 · Cited by 117 · see citing works
Lipopolysaccharide activates Akt in vascular smooth muscle cells resulting in induction of inducible nitric oxide synthase through nuclear factor-kappa B activation
Hattori, Y., Hattori, S., & Kasai, K. (2003) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2003.09.034 · Cited by 105 · see citing works
Inhibition of Inducible Nitric-Oxide Synthase Expression by Silymarin in Lipopolysaccharide-Stimulated Macrophages
Kang, J. S., Jeon, Y. J., Kim, H. M., Han, S. H., & Yang, K. (2002) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.302.1.138 · Cited by 102 · see citing works
Self-citation
Synergistic inhibition of LDL oxidation by phytoestrogens and ascorbic acid
Hwang, J., Sevanian, A., Hodis, H. N., et al. (2000) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(00)00322-1 · Cited by 100 · see citing works
Potential Role of the JNK/SAPK Signal Transduction Pathway in the Induction of iNOS by TNF-α
Chan, E. D., & Riches, D. W. H. (1998) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1998.9857 · Cited by 95 · see citing works
Lipoteichoic acid induces nuclear factor‐κB activation and nitric oxide synthase expression via phosphatidylinositol 3‐kinase, Akt, and p38 MAPK in RAW 264.7 macrophages
Kao, S., Lei, H., Kuo, C., Chang, M., Chen, B.-C., Chang, Y.-C., Chiu, W., & Lin, C. (2005) · Immunology · doi:10.1111/j.1365-2567.2005.02160.x · Cited by 89 · see citing works
Glabridin, an Isoflavan from Licorice Root, Inhibits Inducible Nitric-Oxide Synthase Expression and Improves Survival of Mice in Experimental Model of Septic Shock
Kang, J. S., Yoon, Y. D., Cho, I.-J., Han, M. H., Lee, C. W., Park, S.-K., & Kim, H. M. (2005) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.104.077107 · Cited by 86 · see citing works
Self-citation
Polysaccharide isolated from Poria cocos sclerotium induces NF-κB/Rel activation and iNOS expression in murine macrophages
Lee, K. Y., & Jeon, Y. J. (2003) · International Immunopharmacology · doi:10.1016/s1567-5769(03)00113-9 · Cited by 79 · see citing works
Self-citation
Radicicol suppresses expression of inducible nitric-oxide synthase by blocking p38 kinase and nuclear factor-kappaB/Rel in lipopolysaccharide-stimulated macrophages.
Jeon, Y. J., Kim, Y. K., Lee, M., Park, S. M., Han, S., & Kim, H. M. (2000) · PubMed · Cited by 79 · see citing works
Self-citation
Effect of Chronic Treatment With the Inducible Nitric Oxide Synthase InhibitorN-Iminoethyl- l -Lysine or With l -Arginine on Progression of Coronary and Aortic Atherosclerosis in Hypercholesterolemic Rabbits
Behr‐Roussel, D., Rupin, A., Simonet, S., et al. (2000) · Circulation · doi:10.1161/01.cir.102.9.1033 · Cited by 78 · see citing works
Both p38αMAPK and JNK/SAPK Pathways Are Important for Induction of Nitric-oxide Synthase by Interleukin-1β in Rat Glomerular Mesangial Cells
Guan, Z., Buckman, S. Y., Springer, L. D., & Morrison, A. R. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.51.36200 · Cited by 76 · see citing works
Nitric Oxide Synthase Gene Therapy for Cardiovascular Disease
Chen, A. F., Ren, J., & Miao, C. (2002) · The Japanese Journal of Pharmacology · doi:10.1254/jjp.89.327 · Cited by 49 · see citing works
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
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. (2005) · Biochemical Pharmacology · doi:10.1016/j.bcp.2005.10.009 · Cited by 43 · see citing works
C2-ceramide inhibits LPS-induced nitric oxide production in RAW 264.7 macrophage cells through down-regulating the activation of Akt
Koide, N., Sugiyama, T., Mori, I., et al. (2003) · Journal of Endotoxin Research · doi:10.1179/096805103125001450 · Cited by 20 · see citing works
C 2-ceramide inhibits LPS-induced nitric oxide production in RAW 264.7 macrophage cells through down-regulating the activation of Akt
Koide, N., Sugiyama, T., Mori, I., et al. (2003) · Journal of Endotoxin Research · doi:10.1177/09680519030090020201 · Cited by 17 · see citing works
Acetylaminofluorene inhibits nitric oxide production in LPS-stimulated RAW 264.7 cells by blocking NF-κB/Rel activation
Jeon, Y. J., Han, S. H., Kang, J. S., Koh, W. S., & Yang, K. (1999) · Toxicology Letters · doi:10.1016/s0378-4274(98)00372-5 · Cited by 11 · see citing works
Self-citation

Flagged first, then by citations

Sorted by citations

Interaction of dietary compounds, especially polyphenols, with the intestinal microbiota: a review
Duda-Chodak, A., Tarko, T., Satora, P., & Sroka, P. (2015) · European Journal of Nutrition · doi:10.1007/s00394-015-0852-y · Cited by 599 · see citing works
Skin aging and oxidative stress: Equol’s anti-aging effects via biochemical and molecular mechanisms
Lephart, E. D. (2016) · Ageing Research Reviews · doi:10.1016/j.arr.2016.08.001 · Cited by 325 · see citing works
Chondroitin sulfate extracted from the Styela clava tunic suppresses TNF-α-induced expression of inflammatory factors, VCAM-1 and iNOS by blocking Akt/NF-κB signal in JB6 cells
Xu, C.-X., Jin, H., Chung, Y.-S., Shin, J.-Y., Woo, M.-A., Lee, K.-H., Palmos, G. N., Choi, B.-D., & Cho, M.-H. (2008) · Cancer Letters · doi:10.1016/j.canlet.2008.01.022 · Cited by 59 · see citing works
Self-citation
Anti-inflammatory effects of essential oil isolated from the buds of Cleistocalyx operculatus (Roxb.) Merr and Perry
Dung, N. T., Bajpai, V. K., Yoon, J. I., & Kang, S. C. (2009) · Food and Chemical Toxicology · doi:10.1016/j.fct.2008.11.033 · Cited by 60 · see citing works
Equol’s Anti-Aging Effects Protect against Environmental Assaults by Increasing Skin Antioxidant Defense and ECM Proteins While Decreasing Oxidative Stress and Inflammation
Lephart, E. (2018) · Cosmetics · doi:10.3390/cosmetics5010016 · Cited by 42 · see citing works

Neuronal nitric oxide synthase immunohistochemistry and 4,5-diaminofluorescein diacetate: tools for nitric oxide research
Kasim, N., Branton, R. L., & Clarke, D. J. (2001) · Journal of Neuroscience Methods · doi:10.1016/s0165-0270(01)00387-9 · Cited by 18 · see citing works
[Effects of extracts of cheezheng pain relieving plaster on nitric oxide and iNOS expression in macrophages induced by lipopolysaccharides].
Liu, Y., Peng, S.-Y., Wang, L., et al. (2009) · PubMed · Cited by 2 · see citing works
Effects of Kaempferol and Myricetin on Inducible Nitric Oxide Synthase Expression and Nitric Oxide Production in Rats
Rostoka, E., Baumane, L., Isajevs, S., et al. (2010) · Basic & Clinical Pharmacology & Toxicology · doi:10.1111/j.1742-7843.2009.00526.x · Cited by 28 · see citing works
Relationship of inducible nitric oxide synthase, nitric oxide with tumors
Gao, Z., Gao, W., & Huangfu, H. (2019) · doi:10.3760/cma.j.issn.1006-9801.2019.10.017
THE STUDY ON THE ROLE OF THE SUBSTRATE,INHIBITOR OF NOS AND PROVIDER OF NO IN RABBITS' INFECTION BY EIMERIA STIEDAI
Zhang, X. (2008) · Shandong Nongye Daxue xuebao

Authors: Kang, J. S., Yoon, Y. D., Han, M. H., Han, S.-B., Lee, K., Park, S.-K., & Kim, H. M.
Affiliations: Korea Research Institute of Bioscience and Biotechnology (KR)
Corresponding author: Park, Song-Kyu
Kim, Hwan Mook
ORCID: Kang, Jong Soon
Yoon, Yeo Dae
Han, Sang-Bae
Lee, Kiho
Park, Song-Kyu
Venue: International Immunopharmacology
Publisher: Elsevier BV
Published: 2007-04
Volume: 7
Issue: 4
Pages: 491-499
ISSN: 1567-5769 (ISSN-L)
DOI: 10.1016/j.intimp.2006.12.004
OpenAlex: W2043872076
Cited by: 45
References: 44
Citations by year: 2026: 3 · 2024: 2 · 2023: 2 · 2022: 1 · 2020: 2 · 2019: 2 · 2018: 4 · 2017: 1 · 2016: 7 · 2015: 5 · 2014: 3 · 2013: 2 · 2012: 1
FWCI: 2.36
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: International Immunopharmacology (publishedVersion)
PubMed (publishedVersion)
KRIBB Repository (submittedVersion)
Topics: Health Sciences › Medicine › Pathology and Forensic Medicine › Phytoestrogen effects and research
Health Sciences › Medicine › Complementary and alternative medicine › Natural Compounds in Disease Treatment
Health Sciences › Medicine › Pharmacology › Inflammatory mediators and NSAID effects
Keywords: equol, nitric oxide production, inducible nitric oxide synthase, Akt signaling, NF-κB activation, lipopolysaccharide, macrophages, RAW 264.7 macrophages, phosphatidylinositol 3-kinase, mitogen-activated protein kinase, anti-inflammatory activity
MeSH terms: Animals, Cell Line, Isoflavones, Lipopolysaccharides, Nitric Oxide, RNA, Messenger, Down-Regulation, Gene Expression Regulation, Enzymologic, NF-kappa B, Mitogen-Activated Protein Kinases, Phytoestrogens, Proto-Oncogene Proteins c-akt, Mice, Nitric Oxide Synthase Type II, 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 ›

Are you an author, or do you see a problem with this page? Request a review

Equol inhibits nitric oxide production and inducible nitric oxide synthase gene expression through down-regulating the activation of Akt

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Cites

Cited by

Related

Record

About these checks