Targeting the redox sensitive Nrf2–Keap1 defense pathway in cardiovascular disease: protection afforded by dietary isoflavones
Abstract
Cells have evolved highly regulated defense systems, including the redox sensitive Nrf2-Keap1 signaling pathway involved in the transcriptional activation of phase II defense and antioxidant genes in oxidative stress. Increased generation of reactive oxygen species (ROS) in cardiovascular disease (CVD) leads to impaired endothelial function and reduced nitric oxide (NO) bioavailability. Although epidemiological evidence suggests that diets containing plant-derived isoflavones (phytoestrogens) afford protection against CVDs, supplementation trials have largely reported only marginal health benefits. The molecular mechanisms by which soy isoflavones (genistein, daidzein, and equol) afford protection against oxidative stress in CVD remain to be investigated in large-scale clinical trials. Studies in animal models and cultured vascular cells have established that isoflavones increase eNOS activity and expression and activate the Nrf2-Keap1 signaling pathway, leading to an upregulation of detoxifying and antioxidant defense genes. We review recent advances in the understanding of the signal transduction pathways involved in the activation of endothelial NO production and Nrf2-Keap1-mediated antioxidant gene expression by dietary isoflavones.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
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?
Haem oxygenase is a protector of lipid peroxidation and is part of the MAPK pathway that results in activation of antioxidant genes/enzyme via the Nrf2/KEAP1/ARE pathway.
“It is known from cardiovascular studies examining dietary isoflavones that haem oxygenase is a protector of lipid peroxidation and is part of the mitogen-activated protein kinase (MAPK) pathway that results in the activation of antioxidant genes/enzyme via the Nrf2/KEAP 1/ARE pathway [95].”
Cites
Free Radicals in the Physiological Control of Cell Function
Dröge, W. (2002) · Physiological Reviews · doi:10.1152/physrev.00018.2001 · Cited by 9,855 · see citing works
Kuiper, G. G. J. M., Carlsson, B., Grandien, K., Enmark, E., Häggblad, J., Nilsson, S., & Gustafsson, J.-A. (1997) · Endocrinology · doi:10.1210/endo.138.3.4979 · Cited by 4,442 · see citing works
Itoh, K., Wakabayashi, N., Katoh, Y., Ishii, T., Igarashi, K., Engel, J. D., & Yamamoto, M. (1999) · Genes & Development · doi:10.1101/gad.13.1.76 · Cited by 3,634 · see citing works
Self-citationMechanisms linking obesity with cardiovascular disease
Van Gaal, L. F., Mertens, I. L., & De Block, C. E. (2006) · Nature · doi:10.1038/nature05487 · Cited by 2,814 · see citing works
Role of Oxidative Modifications in Atherosclerosis
Stocker, R., & Keaney, J. F. (2004) · Physiological Reviews · doi:10.1152/physrev.00047.2003 · Cited by 2,611 · see citing works
Heme Oxygenase-1/Carbon Monoxide: From Basic Science to Therapeutic Applications
Ryter, S. W., Alam, J., & Choi, A. M. K. (2006) · Physiological Reviews · doi:10.1152/physrev.00011.2005 · Cited by 2,308 · see citing works
Flavonoids: antioxidants or signalling molecules?
Williams, R. J., Spencer, J. P. E., & Rice-Evans, C. (2004) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2004.01.001 · Cited by 2,016 · see citing works
Moi, P., Chan, K., Asunis, I., Cao, A., & Kan, Y. W. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.21.9926 · Cited by 1,607 · see citing works
Ishii, T., Itoh, K., Takahashi, S., Sato, H., Yanagawa, T., Katoh, Y., Bannai, S., & Yamamoto, M. P. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.21.16023 · Cited by 1,460 · see citing works
Self-citationBioavailability and bioefficacy of polyphenols in humans. II. Review of 93 intervention studies
Williamson, G., & Manach, C. (2005) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/81.1.243s · Cited by 1,340 · see citing works
Phyto-oestrogens and Western Diseases
Adlercreutz, H., & Mazur, W. (1997) · Annals of Medicine · doi:10.3109/07853899709113696 · Cited by 1,280 · see citing works
Nrf2 signaling in coordinated activation of antioxidant gene expression
Jaiswal, A. K. (2004) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2004.02.074 · Cited by 1,254 · see citing works
Dietary Isoflavones: Biological Effects and Relevance to Human Health
Setchell, K. D. R., & Cassidy, A. (1999) · Journal of Nutrition · doi:10.1093/jn/129.3.758s · Cited by 1,158 · see citing works
McMahon, M., Itoh, K., Yamamoto, M., & Hayes, J. D. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m300931200 · Cited by 1,141 · see citing works
Phytoestrogens: the biochemistry, physiology, and implications for human health of soy isoflavones
Setchell, K. D. R. (1998) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/68.6.1333s · Cited by 1,137 · see citing works
Molecular and Cellular Basis of Cardiovascular Gender Differences
Mendelsohn, M. E., & Karas, R. H. (2005) · Science · doi:10.1126/science.1112062 · Cited by 1,101 · see citing works
Regulation of inflammation and redox signaling by dietary polyphenols
Rahman, I., Biswas, S. K., & Kirkham, P. (2006) · Biochemical Pharmacology · doi:10.1016/j.bcp.2006.07.004 · Cited by 992 · see citing works
Dolinoy, D. C., Weidman, J. R., Waterland, R. A., & Jirtle, R. L. (2006) · Environmental Health Perspectives · doi:10.1289/ehp.8700 · Cited by 932 · see citing works
Itoh, K., Tong, K. I., & Yamamoto, M. P. (2004) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2004.02.075 · Cited by 866 · see citing works
Kobayashi, M., & Yamamoto, M. P. (2006) · Advances in Enzyme Regulation · doi:10.1016/j.advenzreg.2006.01.007 · Cited by 855 · see citing works
Surh, Y., Kundu, J. K., & Na, H. (2008) · Planta Medica · doi:10.1055/s-0028-1088302 · Cited by 759 · see citing works
Stroka, D., Burkhardt, T., Desbaillets, I., Wenger, R. H., Neil, D., Bauer, C., GASSMANN, M., & Candinas, D. (2001) · The FASEB Journal · doi:10.1096/fj.01-0125com · Cited by 716 · see citing works
Nutrigenomics: goals and strategies
Müller, M. M., & Kersten, S. (2003) · Nature Reviews Genetics · doi:10.1038/nrg1047 · Cited by 645 · see citing works
Acute Activation of Maxi-K Channels ( hSlo ) by Estradiol Binding to the β Subunit
Valverde, M. A., Rojas, P., Amigo, J. D., Cosmelli, D. J., Orio, P., Bahamonde, M. I., Mann, G. E., Vergara, C., & Latorre, R. (1999) · Science · doi:10.1126/science.285.5435.1929 · Cited by 508 · see citing works
Self-citationMcMahon, M. J., Thomas, N., Itoh, K., Yamamoto, M. P., & Hayes, J. D. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m601119200 · Cited by 489 · see citing works
Jain, A. K., & Jaiswal, A. K. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m611336200 · Cited by 484 · see citing works
Setchell, K. D., Clerici, C., Lephart, E. D., Cole, S. J., Heenan, C., Castellani, D., Wolfe, B. E., Nechemias-Zimmer, L., Brown, N. M., Lund, T. D., et al. (2005) · The American Journal of Clinical Nutrition · doi:10.1093/ajcn/81.5.1072 · Cited by 471 · see citing works
Tong, K. I., Padmanabhan, B., Kobayashi, A., Shang, C., Hirotsu, Y., Yokoyama, S., & Yamamoto, M. P. (2007) · Molecular and Cellular Biology · doi:10.1128/mcb.00753-07 · Cited by 447 · see citing works
McMahon, M. J., Thomas, N., Itoh, K., Yamamoto, M. P., & Hayes, J. D. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m403061200 · Cited by 406 · see citing works
Role of Nrf2 in the Regulation of CD36 and Stress Protein Expression in Murine Macrophages
Ishii, T., Itoh, K., Ruiz, E., Leake, D. S., Unoki‐Kubota, H., Yamamoto, M. P., & Mann, G. E. (2004) · Circulation Research · doi:10.1161/01.res.0000119171.44657.45 · Cited by 400 · see citing works
Self-citationRedox Mechanisms in Blood Vessels
Mueller, C. F. H., Laude, K. M., McNally, J. S., & Harrison, D. G. (2004) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000149143.04821.eb · Cited by 342 · see citing works
Laminar Flow Induction of Antioxidant Response Element-mediated Genes in Endothelial Cells
Chen, X.-L., Varner, S. E., Rao, A. S., Grey, J. Y., Thomas, S., Cook, C. K., Wasserman, M. A., Medford, R. M., Jaiswal, A. K., & Kunsch, C. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m203161200 · Cited by 333 · see citing works
Nrf1 and Nrf2 Play Distinct Roles in Activation of Antioxidant Response Element-dependent Genes
Ohtsuji, M., Katsuoka, F., Kobayashi, A., Aburatani, H., Hayes, J. D., & Yamamoto, M. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m804597200 · Cited by 317 · see citing works
Phytoestrogens and cardiovascular health
Wroblewski Lissin, L., & Cooke, J. P. (2000) · Journal of the American College of Cardiology · doi:10.1016/s0735-1097(00)00590-8 · Cited by 286 · see citing works
Siow, R. C. M. (1999) · Cardiovascular Research · doi:10.1016/s0008-6363(98)00278-8 · Cited by 274 · see citing works
Self-citationViña, J., Borrás, C., Gambini, J., Sastre, J., & Pallardó, F. V. (2005) · FEBS Letters · doi:10.1016/j.febslet.2005.03.090 · Cited by 271 · see citing works
Cassidy, A., Brown, J. E., Hawdon, A., Faughnan, M. S., King, L. J., Millward, J., Zimmer-Nechemias, L., Wolfe, B., & Setchell, K. D. R. (2006) · Journal of Nutrition · doi:10.1093/jn/136.1.45 · Cited by 256 · see citing works
Dai, G., Vaughn, S., Zhang, Y., Wang, E. T., García‐Cardeña, G., & Gimbrone, M. A. (2007) · Circulation Research · doi:10.1161/circresaha.107.152942 · Cited by 245 · see citing works
de Kleijn, M. J. J., van der Schouw, Y. T., Wilson, P. W. F., Grobbee, D. E., & Jacques, P. F. (2002) · Journal of Nutrition · doi:10.1093/jn/132.2.276 · Cited by 228 · see citing works
Hosoya, T., Maruyama, A., Kang, M.-I., Kawatani, Y., Shibata, T., Uchida, K., Itoh, K., & Yamamoto, M. P. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m502551200 · Cited by 227 · see citing works
Mahn, K., Borrás, C., Knock, G., Taylor, P., Khan, I. Y., Sugden, D., Poston, L., Ward, J., Sharpe, R., Viña, J., et al. (2005) · The FASEB Journal · doi:10.1096/fj.05-4008fje · Cited by 201 · see citing works
Self-citationDietary isoflavones in the prevention of cardiovascular disease – A molecular perspective
Rimbach, G. H., Boesch, C., Frank, J., Fuchs, D., Wenzel, U., Daniel, H., Hall, W. L., & Weinberg, P. D. (2007) · Food and Chemical Toxicology · doi:10.1016/j.fct.2007.06.029 · Cited by 193 · see citing works
Walker, H. A., Dean, T. S., Sanders, T. A. B., Jackson, G., Ritter, J. M., & Chowienczyk, P. (2001) · Circulation · doi:10.1161/01.cir.103.2.258 · Cited by 189 · see citing works
Levonen, A., Inkala, M., Heikura, T., Jauhiainen, S., Jyrkkänen, H.-K., Kansanen, E., Määttä, K. M., Romppanen, E., Turunen, P., Rutanen, J., et al. (2007) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000258868.80079.4d · Cited by 189 · see citing works
Mann, G. E., Rowlands, D. J., Li, F., deWinter, P., & Siow, R. (2007) · Cardiovascular Research · doi:10.1016/j.cardiores.2007.04.004 · Cited by 181 · see citing works
Self-citationBorrás, C., Gambini, J., Gómez‐Cabrera, M. C., Sastre, J., Pallardó, F. V., Mann, G. E., & Viña, J. (2006) · The FASEB Journal · doi:10.1096/fj.05-5522fje · Cited by 180 · see citing works
Self-citationWarabi, E., Takabe, W., Minami, T., Inoue, K., Itoh, K., Yamamoto, M. P., Ishii, T., Kodama, T., & Noguchi, N. (2006) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2006.10.043 · Cited by 165 · see citing works
Self-citationMaternal and neonatal phytoestrogens in Japanese women during birth
Adlercreutz, H., Yamada, T., Wähälä, K., & Watanabe, S. (1999) · American Journal of Obstetrics and Gynecology · doi:10.1016/s0002-9378(99)70281-4 · Cited by 164 · see citing works
The WHI Estrogen-Alone Trial—Do Things Look Any Better?
Hulley, S. B. (2004) · JAMA · doi:10.1001/jama.291.14.1769 · Cited by 156 · see citing works
McCarty, M. F. (2006) · Medical Hypotheses · doi:10.1016/j.mehy.2004.11.046 · Cited by 155 · see citing works
Effect of Gender on NADPH-Oxidase Activity, Expression, and Function in the Cerebral Circulation
Miller, A. A., Drummond, G. R., Mast, A., Schmidt, H. H. H. W., & Sobey, C. G. (2007) · Stroke · doi:10.1161/strokeaha.106.477406 · Cited by 155 · see citing works
Ruehlmann, D. O., Steinert, J. R., Valverde, M. A., Jacob, R., & Mann, G. E. (1998) · The FASEB Journal · doi:10.1096/fasebj.12.7.613 · Cited by 143 · see citing works
Self-citationThe Isoflavone Equol Mediates Rapid Vascular Relaxation
Joy, S., Siow, R. C. M., Rowlands, D. J., Becker, M., Wyatt, A. W., Aaronson, P. I., Coen, C. W., Kalló, I., Jacob, R., & Mann, G. E. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m602803200 · Cited by 141 · see citing works
Self-citationSiow, R. C. M., Li, F. Y. L., Rowlands, D. J., de Winter, P., & Mann, G. E. (2007) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2007.01.004 · Cited by 135 · see citing works
Self-citationSi, H., & Liu, D. (2008) · Journal of Nutrition · doi:10.1093/jn/138.2.297 · Cited by 135 · see citing works
Tamoxifen Activates Smooth Muscle BK Channels through the Regulatory β1 Subunit
Dick, G. M., Rossow, C. F., Sv, S., Horowitz, B., & Sanders, K. M. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m104689200 · Cited by 128 · see citing works
Fetal exposure to phytoestrogens—The difference in phytoestrogen status between mother and fetus
Todaka, E., Sakurai, K., Fukata, H., Miyagawa, H., Uzuki, M., Omori, M., Osada, H., Ikezuki, Y., Tsutsumi, O., Iguchi, T., et al. (2005) · Environmental Research · doi:10.1016/j.envres.2004.11.006 · Cited by 128 · see citing works
Wyatt, A. W., Steinert, J. R., Wheeler-Jones, C. P. D., Morgan, A. J., Sugden, D., Pearson, J. D., Sobrevía, L., & Mann, G. E. (2002) · The FASEB Journal · doi:10.1096/fasebj.16.12.1584 · Cited by 127 · see citing works
Self-citationAnwar, A. A., Li, F. Y. L., Leake, D. S., Ishii, T., Mann, G. E., & Siow, R. C. M. (2005) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2005.03.012 · Cited by 122 · see citing works
Self-citationAntioxidant Gene Therapy for Cardiovascular Disease
Levonen, A., Vähäkangas, E., Koponen, J. K., & Ylä‐Herttuala, S. (2008) · Circulation · doi:10.1161/circulationaha.107.718585 · Cited by 113 · see citing works
Liu, D., Homan, L. L., & Dillon, J. S. (2004) · Endocrinology · doi:10.1210/en.2004-0102 · Cited by 112 · see citing works
Kreijkamp‐Kaspers, S., Kok, L., Bots, M. L., Grobbee, D. E., Lampe, J. W., & van der Schouw, Y. T. (2005) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/81.1.189 · Cited by 112 · see citing works
Probucol Protects Against Smooth Muscle Cell Proliferation by Upregulating Heme Oxygenase-1
Deng, Y., Wu, B. J., Witting, P. K., & Stocker, R. (2004) · Circulation · doi:10.1161/01.cir.0000142610.10530.25 · Cited by 106 · see citing works
Villa, P., Costantini, B., Suriano, R., Perri, C., Macrì, F., Ricciardi, L., Panunzi, S., & Lanzone, A. (2008) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2008-0735 · Cited by 105 · see citing works
Soy Protein, Isoflavones, and Cardiovascular Health
Sacks, F. M., Lichtenstein, A. H., Horn, L. V., Harris, W. S., Kris‐Etherton, P. M., & Winston, M. C. (2006) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000227471.00284.ef · Cited by 104 · see citing works
Trujillo, J., Ramírez, V., Pérez, J., Torre-Villalvazo, I., Torres, N., Tovar, A. R., Muñoz, R. M., Uribe, N., Gamba, G., & Bobadilla, N. A. (2004) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00077.2004 · Cited by 76 · see citing works
Phytoestrogens and cardiovascular disease
Cassidy, A., & Hooper, L. (2006) · The Journal of the British Menopause Society · doi:10.1258/136218006777525776 · Cited by 73 · see citing works
Nestel, P. J., Fujii, A., & Zhang, L. (2006) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2006.04.033 · Cited by 68 · see citing works
Hall, W. L., Formanuik, N. L., Harnpanich, D., Cheung, M., Talbot, D. C. S., Chowienczyk, P., & Sanders, T. A. B. (2008) · Journal of Nutrition · doi:10.1093/jn/138.7.1288 · Cited by 64 · see citing works
Cardiovascular Effects of the Phytoestrogen Genistein
Altavilla, D., Crisafulli, A., Marini, H. R., Esposito, M., D’Anna, R., Corrado, F., Bitto, A., & Squadrito, F. (2004) · Current Medicinal Chemistry - Cardiovascular & Hematological Agents · doi:10.2174/1568016043477297 · Cited by 63 · see citing works
Xu, J., Ikeda, K., & Yamori, Y. (2004) · Hypertension Research · doi:10.1291/hypres.27.675 · Cited by 50 · see citing works
Törmälä, R., Appt, S. E., Clarkson, T. B., Groop, P., Rönnback, M., Ylikorkala, O., & Mikkola, T. S. (2007) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2007.09.010 · Cited by 44 · see citing works
Chin-Dusting, J. P. F., Boak, L. M., Husband, A., & Nestel, P. J. (2004) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2004.03.025 · Cited by 34 · see citing works
Cardiovascular consequences of life‐long exposure to dietary isoflavones in the rat
Douglas, G., Armitage, J. A., Taylor, P. D., Lawson, J. R., Mann, G. E., & Poston, L. (2006) · The Journal of Physiology · doi:10.1113/jphysiol.2005.104125 · Cited by 19 · see citing works
Self-citationKreijkamp‐Kaspers, S., Kok, L., Bots, M. L., Lampe, J. W., van der Schouw, Y. T., & Grobbee, D. E. (2004) · Journal of Hypertension · doi:10.1097/00004872-200406002-00895 · Cited by 16 · see citing works
Knock, G. A., Mahn, K., Mann, G. E., Ward, J. P. T., & Aaronson, P. I. (2006) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2006.05.017 · Cited by 15 · see citing works
Self-citationNutrients: the environmental regulation of cardiovascular gene expression
Minieri, M., & Nardo, P. D. (2007) · Genes & Nutrition · doi:10.1007/s12263-007-0048-z · Cited by 9 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Magesh, S., Chen, Y., & Hu, L. (2012) · Medicinal Research Reviews · doi:10.1002/med.21257 · Cited by 760 · see citing works
Identification of novel NRF2-regulated genes by ChIP-Seq: influence on retinoid X receptor alpha
Chorley, B. N., Campbell, M. R., Wang, X., Karaca, M., Sambandan, D., Bangura, F., Xue, P., Pi, J., Kleeberger, S. R., & Bell, D. A. (2012) · Nucleic Acids Research · doi:10.1093/nar/gks409 · Cited by 557 · 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
Isoflavones: Anti-Inflammatory Benefit and Possible Caveats
Yu, J., Bi, X., Yu, B., & Chen, D. (2016) · Nutrients · doi:10.3390/nu8060361 · Cited by 294 · see citing works
Singh, S., Vrishni, S., Singh, B. K., Rahman, I., & Kakkar, P. (2010) · Free Radical Research · doi:10.3109/10715762.2010.507670 · Cited by 294 · see citing works
Torres, N., Guevara‐Cruz, M., Velázquez‐Villegas, L. A., & Tovar, A. R. (2015) · Archives of Medical Research · doi:10.1016/j.arcmed.2015.05.010 · Cited by 273 · see citing works
Antioxidant actions of flavonoids: Thermodynamic and kinetic analysis
Galleano, M., Verstraeten, S. V., Oteiza, P. I., & Fraga, C. G. (2010) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2010.04.005 · Cited by 248 · see citing works
NRF2 targeting: a promising therapeutic strategy in chronic obstructive pulmonary disease
Boutten, A., Goven, D., Artaud-Macari, É., Boczkowski, J., & Bonay, M. (2011) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2011.02.006 · Cited by 223 · see citing works
Cheng, X., Ku, C.-H., & Siow, R. C. M. (2013) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2013.07.025 · Cited by 217 · see citing works
Self-citationChapple, S. J., Siow, R. C. M., & Mann, G. E. (2012) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2012.04.021 · Cited by 216 · see citing works
Self-citationTargeting the Nrf2–Keap1 antioxidant defence pathway for neurovascular protection in stroke
Alfieri, A., Srivastava, S., Siow, R. C. M., Modo, M., Fraser, P. A., & Mann, G. E. (2011) · The Journal of Physiology · doi:10.1113/jphysiol.2011.210294 · Cited by 198 · see citing works
Self-citationEmerging evidence of the health benefits of S-equol, an estrogen receptor β agonist
Jackson, R. L., Greiwe, J. S., & Schwen, R. J. (2011) · Nutrition Reviews · doi:10.1111/j.1753-4887.2011.00400.x · Cited by 195 · see citing works
The potential of flavonoids in the treatment of non-alcoholic fatty liver disease
van de Wier, B., Koek, G. H., Bast, A., & Haenen, G. R. M. M. (2015) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2014.952399 · Cited by 192 · see citing works
Cheng, X., Siow, R. C. M., & Mann, G. E. (2010) · Antioxidants and Redox Signaling · doi:10.1089/ars.2010.3283 · Cited by 181 · see citing works
Self-citationChocolate and the brain: Neurobiological impact of cocoa flavanols on cognition and behavior
Sokolov, A. N., Pavlova, M. A., Klosterhalfen, S., & Enck, P. (2013) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2013.06.013 · Cited by 178 · see citing works
Liu, T., Lv, Y., Zhao, J., You, Q., & Jiang, Z. (2021) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2021.03.034 · Cited by 172 · see citing works
Targeting the Nrf2 pathway against cardiovascular disease
Li, J., Ichikawa, T., Janicki, J. S., & Cui, T. (2009) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728220903025762 · Cited by 168 · see citing works
Varı́, R., D’Archivio, M., Filesi, C., Carotenuto, S., Scazzocchio, B., Santangelo, C., Giovannini, C., & Masella, R. (2010) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2010.03.008 · Cited by 171 · see citing works
Dysfunctional Nrf2–Keap1 redox signaling in skeletal muscle of the sedentary old
Safdar, A., DeBeer, J., & Tarnopolsky, M. A. (2010) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2010.08.010 · Cited by 158 · see citing works
Rodríguez‐Ramiro, I., Ramos, S., Bravo, L., Goya, L., & Martín, M. Á. (2011) · European Journal of Nutrition · doi:10.1007/s00394-011-0269-1 · Cited by 142 · see citing works
Zhai, X., Lin, M., Zhang, F., Hu, Y. W., Xu, X., Li, Y., Liu, K., Ma, X., Tian, X., & Yao, J. (2012) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201200536 · Cited by 134 · see citing works
Phytoestrogens and the metabolic syndrome
Jungbauer, A., & Medjakovic, S. (2013) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2012.12.009 · Cited by 128 · see citing works
Davinelli, S., Saso, L., D’Angeli, F., Calabrese, V., Intrieri, M., & Scapagnini, G. (2022) · Molecules · doi:10.3390/molecules27020502 · Cited by 125 · see citing works
Mitochondria: Redox Metabolism and Dysfunction
Kang, J., & Pervaiz, S. (2012) · Biochemistry Research International · doi:10.1155/2012/896751 · Cited by 121 · see citing works
Siow, R. C. M., & Mann, G. E. (2010) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2010.09.003 · Cited by 119 · see citing works
Self-citationSrivastava, S., Blower, P. J., Aubdool, A. A., Hider, R. C., Mann, G. E., & Siow, R. C. M. (2016) · Scientific Reports · doi:10.1038/s41598-016-0012-5 · Cited by 112 · see citing works
Self-citationHormetics: Dietary Triggers of an Adaptive Stress Response
Birringer, M. (2011) · Pharmaceutical Research · doi:10.1007/s11095-011-0551-1 · Cited by 97 · see citing works
Pizzimenti, S., Toaldo, C., Pettazzoni, P., Dianzani, M. U., & Barrera, G. (2010) · Cancers · doi:10.3390/cancers2020338 · Cited by 96 · see citing works
Imai, S. (2010) · Pharmacological Research · doi:10.1016/j.phrs.2010.01.006 · Cited by 89 · see citing works
Induction of human fetal hemoglobin via the NRF2 antioxidant response signaling pathway
Macari, E. R., & Lowrey, C. H. (2011) · Blood · doi:10.1182/blood-2010-10-314096 · Cited by 87 · see citing works
Zhu, L.-H., Wang, L., Wang, D., Jiang, H., Tang, Q., Yan, L., Bian, Z., Wang, X.-A., & Li, H. (2009) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2009.10.040 · Cited by 85 · see citing works
Recent advances in pancreatic cancer: biology, treatment, and prevention
Singh, D. K., Upadhyay, G., Srivastava, R. K., & Shankar, S. (2015) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2015.04.003 · Cited by 84 · see citing works
Mulvaney, K. M., Matson, J. P., Siesser, P. F., Tamir, T. Y., Goldfarb, D., Jacobs, T. M., Cloer, E. W., Harrison, J. S., Vaziri, C., Cook, J. G., et al. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m116.729418 · Cited by 82 · see citing works
Zhang, T., Liang, X., Shi, L., Wang, L., Chen, J., Kang, C., Zhu, J., & Mi, M. (2013) · PLoS ONE · doi:10.1371/journal.pone.0079075 · Cited by 80 · see citing works
Intake of Soy, Soy Isoflavones and Soy Protein and Risk of Cancer Incidence and Mortality
Fan, Y., Wang, M., Li, Z., Jiang, H., Shi, J., Shi, X., Liu, S., Zhao, J., Kong, L., Zhang, W., et al. (2022) · Frontiers in Nutrition · doi:10.3389/fnut.2022.847421 · Cited by 84 · see citing works
Májková, Z., Layne, J. D., Sunkara, M., Morris, A. J., Toborek, M. J., & Hennig, B. (2010) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2010.11.013 · Cited by 80 · see citing works
Daidzein ameliorates LPS-induced hepatocyte injury by inhibiting inflammation and oxidative stress
Yu, Z., Liu, Y., Deng, S., & Liang, M. (2020) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2020.173399 · Cited by 78 · see citing works
The Regulatory Effect of Phytochemicals on Chronic Diseases by Targeting Nrf2-ARE Signaling Pathway
He, W., Lv, C., Chen, Z., Shi, M., Zeng, C., Hou, D., & Qin, S. (2023) · Antioxidants · doi:10.3390/antiox12020236 · Cited by 76 · see citing works
Leonardo, C. C., & Doré, S. (2011) · Nutritional Neuroscience · doi:10.1179/1476830511y.0000000013 · Cited by 77 · see citing works
Jung, D., Ha, H., Zheng, X., Chang, Y., & Williams, D. R. (2010) · Molecular BioSystems · doi:10.1039/c0mb00089b · Cited by 77 · see citing works
Nrf2 as an Endothelial Mechanosensitive Transcription Factor
McSweeney, S. R., Warabi, E., & Siow, R. C. M. (2015) · Hypertension · doi:10.1161/hypertensionaha.115.06146 · Cited by 77 · see citing works
Self-citationSappanone A exhibits anti-inflammatory effects via modulation of Nrf2 and NF-κB
Lee, S.-H., Choi, S.-Y., Choo, Y.-Y., Kim, O., Trần, P. T., Dao, C. T., Min, B.-S., & Lee, J. (2015) · International Immunopharmacology · doi:10.1016/j.intimp.2015.06.015 · Cited by 73 · see citing works
Selenium and diabetes: an enigma?
Mueller, A. S., Mueller, K., Wolf, N. M., & Pallauf, J. (2009) · Free Radical Research · doi:10.1080/10715760903196925 · Cited by 72 · see citing works
Kobatake, E., Nakagawa, H., Seki, T., & Miyazaki, T. (2017) · PLoS ONE · doi:10.1371/journal.pone.0177106 · Cited by 69 · see citing works
Genistein alleviates pressure overload‐induced cardiac dysfunction and interstitial fibrosis in mice
Qin, W., Du, N., Zhang, L., Wu, X., Hu, Y., Li, X., Shen, N., Li, Y., Yang, B., Xu, C., et al. (2014) · British Journal of Pharmacology · doi:10.1111/bph.13002 · Cited by 69 · see citing works
Wu, P.-S., Ding, H., Yen, J.-H., Chen, S.-F., Lee, K., & Wu, M. (2018) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.8b00437 · Cited by 69 · see citing works
Bruyne, T. D., Steenput, B., Roth, L., Meyer, G. R. Y. D., dos Santos, C. N., Valentová, K., Dambrova, M., & Hermans, N. (2019) · Nutrients · doi:10.3390/nu11030578 · Cited by 68 · see citing works
Cox, K. B., Liu, J., Tian, L., Barnes, S., Yang, Q., & Wood, P. A. (2009) · Laboratory Investigation · doi:10.1038/labinvest.2009.86 · Cited by 66 · see citing works
Makabe, S., Takahashi, Y., Watanabe, H., Murakami, M., Ohba, T., & Ito, H. (2010) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2010.07.059 · Cited by 53 · see citing works
MiR-34b Protects Against Focal Cerebral Ischemia-Reperfusion (I/R) Injury in Rat by Targeting Keap1
Rong, H., Ma, J., Niu, B., Li, J., Chang, J. H., Zhang, Y., Liu, P., & Luan, X. (2018) · Journal of Stroke and Cerebrovascular Diseases · doi:10.1016/j.jstrokecerebrovasdis.2018.08.023 · Cited by 53 · see citing works
Leoncini, E., Malaguti, M., Angeloni, C., Motori, E., Fabbri, D., & Hrelia, S. (2011) · Journal of Food Science · doi:10.1111/j.1750-3841.2011.02311.x · Cited by 51 · see citing works
New Treatment Strategies for Alcohol-Induced Heart Damage
Fernández‐Solà, J., & Porta, A. P. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms17101651 · Cited by 49 · see citing works
Shlomai, J. (2010) · Antioxidants and Redox Signaling · doi:10.1089/ars.2009.3029 · Cited by 47 · see citing works
Sun, X., Zuo, H., Liu, C., & Yang, Y. (2016) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2016.2719 · Cited by 48 · see citing works
The Role of Plant-derived Products in Pancreatitis: Experimental and Clinical Evidence
Anchi, P., Khurana, A., Bale, S., & Godugu, C. (2017) · Phytotherapy Research · doi:10.1002/ptr.5792 · Cited by 47 · see citing works
Targeted antioxidant therapies in hyperglycemia-mediated endothelial dysfunction
de Haan, J. B. (2010) · Frontiers in Bioscience-Scholar · doi:10.2741/s182 · Cited by 47 · see citing works
Why tocotrienols work better: insights into the in vitro anti-cancer mechanism of vitamin E
Viola, V., Pilolli, F., Piroddi, M., Pierpaoli, E., Orlando, F., Provinciali, M., Betti, M., Mazzini, F., & Galli, F. (2011) · Genes & Nutrition · doi:10.1007/s12263-011-0219-9 · Cited by 46 · see citing works
Evidence for genistein as a mitochondriotropic molecule
de Oliveira, M. R. (2016) · Mitochondrion · doi:10.1016/j.mito.2016.05.005 · Cited by 45 · see citing works
Ruan, Q., Ruan, J., Zhang, W., Qian, F., & Yu, Z. (2017) · Pharmacological Research · doi:10.1016/j.phrs.2017.08.010 · Cited by 44 · see citing works
Dose-dependent deleterious and salutary actions of the Nrf2 inducer dh404 in chronic kidney disease
Vaziri, N. D., Liu, S., Farzaneh, S. H., Nazertehrani, S., Khazaeli, M., & Zhao, Y. (2015) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2015.04.022 · Cited by 44 · see citing works
Piesche, M., Roos, J., Kuhn, B. R., Fettel, J., Hellmuth, N., Brat, C., Maucher, I. V., Awad, O., Matrone, C., Comerma-Steffensen, S., et al. (2020) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.01297 · Cited by 44 · see citing works
Bonacasa, B., Siow, R. C. M., & Mann, G. E. (2011) · Microcirculation · doi:10.1111/j.1549-8719.2011.00088.x · Cited by 43 · see citing works
Self-citationRodrigues, F., Almeida, I. M. C., Sarmento, B. F. C. C., Amaral, M. H., & Oliveira, M. B. P. P. (2014) · Industrial Crops and Products · doi:10.1016/j.indcrop.2014.03.014 · Cited by 43 · see citing works
Targeting Abdominal Obesity and Its Complications with Dietary Phytoestrogens
Kuryłowicz, A., Cakala, M., & Puzianowska‐Kuźnicka, M. (2020) · Nutrients · doi:10.3390/nu12020582 · Cited by 43 · see citing works
Kim, S. H., Kim, S. H., Choi, M., Lee, Y., Kim, Y. O., Ahn, D. S., Kim, Y., Kang, E. S., Lee, E. J., Jung, M., et al. (2010) · Cardiovascular Research · doi:10.1093/cvr/cvq089 · Cited by 41 · see citing works
A new skeleton flavonoid and a new lignan from Portulaca oleracea L. and their activities
Duan, Y., Ying, Z., He, F., Ying, X., Jia, L., & Yang, G. (2021) · Fitoterapia · doi:10.1016/j.fitote.2021.104993 · Cited by 41 · see citing works
Chemical characterization and antioxidant properties of Canadian propolis
Naggar, Y. A., Sun, J., Robertson, A. J., Giesy, J. P., & Wiseman, S. B. (2016) · Journal of Apicultural Research · doi:10.1080/00218839.2016.1233700 · Cited by 40 · see citing works
Hsu, W.-H., Lee, B., & Pan, T. (2014) · Journal of Agricultural and Food Chemistry · doi:10.1021/jf501373a · Cited by 39 · see citing works
Khanna, A. K., Xu, J., & Mehra, M. R. (2011) · Laboratory Investigation · doi:10.1038/labinvest.2011.146 · Cited by 38 · see citing works
Li, H.-Y., Pan, L., Ke, Y., Batnasan, E., Jin, X., Liu, Z., & Ba, X. (2014) · Acta Pharmacologica Sinica · doi:10.1038/aps.2013.191 · Cited by 37 · see citing works
Wu, X., Huang, L., & Liu, J. (2021) · Experimental and Therapeutic Medicine · doi:10.3892/etm.2021.10110 · Cited by 37 · see citing works
Pleiotropic Effects of Isoflavones in Inflammation and Chronic Degenerative Diseases
Bernatonienė, J., Kazlauskaitė, J. A., & Kopustinskienė, D. M. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22115656 · Cited by 37 · see citing works
Laurindo, L. F., de Maio, M. C., Minniti, G., Corrêa, N. D. G., Barbalho, S. M., Quesada, K. R., Guiguer, É. L., Sloan, K. P., Detregiachi, C. R. P., Araújo, A. C., et al. (2023) · Metabolites · doi:10.3390/metabo13020243 · Cited by 37 · see citing works
Hwang, A.-R., Han, J.-H., Lim, J. H., Kang, Y. J., & Woo, C.-H. (2017) · PLoS ONE · doi:10.1371/journal.pone.0178278 · Cited by 36 · see citing works
Ferguson, J. F., Ryan, M., Gibney, E. R., Brennan, L., Roche, H. M., & Reilly, M. P. (2014) · Nutrition Metabolism and Cardiovascular Diseases · doi:10.1016/j.numecd.2014.03.010 · Cited by 35 · see citing works
Genistein: mechanisms of action for a pleiotropic neuroprotective agent in stroke
Schreihofer, D. A., & Oppong‐Gyebi, A. (2017) · Nutritional Neuroscience · doi:10.1080/1028415x.2017.1391933 · Cited by 35 · see citing works
Chen, L., Zhang, B., & Saatman, K. E. (2019) · Neural Regeneration Research · doi:10.4103/1673-5374.265545 · Cited by 32 · see citing works
Graeser, A.-C., Boesch, C., Lippmann, J., Wagner, A. E., Huebbe, P., Storm, N., Höppner, W., Wiswedel, I., Gardemann, A., Minihane, A. M., et al. (2011) · Journal of Molecular Medicine · doi:10.1007/s00109-011-0771-1 · Cited by 31 · see citing works
Yamashita, Y., Nakamura, A., Nanba, F., Saito, S., Toda, T., Nakagawa, J., & Ashida, H. (2020) · Nutrients · doi:10.3390/nu12092755 · Cited by 28 · see citing works
Choo, Y.-Y., Lee, S.-H., Nguyễn, P. H., Lee, W., Woo, M., Min, B.-S., & Lee, J. (2015) · RSC Advances · doi:10.1039/c4ra13847c · Cited by 27 · see citing works
TONG, Y.-F., LIU, Y., HU, Z.-X., LI, Z.-C., & AGULA, A. (2015) · Experimental and Therapeutic Medicine · doi:10.3892/etm.2015.2896 · Cited by 27 · see citing works
Rudkowska, I., Ponton, A., Jacques, H., Lavigne, C., Holub, B. J., Marette, A., & Vohl, M. (2011) · Lifestyle Genomics · doi:10.1159/000330226 · Cited by 26 · see citing works
Al‐Saeedi, F. J. (2020) · Clinical and Experimental Pharmacology and Physiology · doi:10.1111/1440-1681.13432 · Cited by 25 · see citing works
Soumyakrishnan, S., & Sudhandiran, G. (2011) · Biomedicine & Preventive Nutrition · doi:10.1016/j.bionut.2011.09.005 · Cited by 25 · see citing works
Xiao, H., Lu, F.-L., Stewart, D., & Zhang, Y. (2013) · Current Chemical Biology · doi:10.2174/2212796811307020008 · Cited by 25 · see citing works
Nitric oxide up-regulates endothelial expression of angiotensin II type 2 receptors
Dao, V. T.-V., Medini, S., Bisha, M., Balz, V., Suvorava, T., Baş, M., & Kojda, G. (2016) · Biochemical Pharmacology · doi:10.1016/j.bcp.2016.05.011 · Cited by 25 · see citing works
Zhang, S., Xu, S., Duan, H., Zhu, Z., Yang, Z., Cao, J., Zhao, Y., Huang, Z., Wu, Q., & Duan, J. (2019) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2019.03.024 · Cited by 24 · see citing works
Birru, R. L., Ahuja, V., Vishnu, A., Evans, R. W., Miyamoto, Y., Miura, K., Usui, T., & Sekikawa, A. M. (2016) · Journal of Nutritional Science · doi:10.1017/jns.2016.18 · Cited by 23 · see citing works
Wu, P.-S., Yen, J.-H., Wang, C., Chen, P., Hung, J., & Wu, M. (2020) · Biomedicines · doi:10.3390/biomedicines8110506 · Cited by 23 · see citing works
Sies, H., Hollman, P. C. H., Grune, T., Stahl, W., Biesalski, H. K., & Williamson, G. (2012) · Advances in Nutrition · doi:10.3945/an.111.001578 · Cited by 22 · see citing works
Drew, J. E. (2012) · Advances in Nutrition · doi:10.3945/an.112.002121 · Cited by 22 · see citing works
Vascular Protective Effects of Fruit Polyphenols
Habauzit, V., Milenković, D., & Morand, C. (2013) · Polyphenols in Human Health and Disease · doi:10.1016/b978-0-12-398456-2.00068-2 · Cited by 22 · see citing works
Tumova, S., Kerimi, A., & Williamson, G. (2019) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2019.04.023 · Cited by 22 · see citing works
Yuan-jing, F., Wei, W., Jian-ping, L., Jin, Y., & Zi-ling, D. (2016) · Food & Function · doi:10.1039/c6fo00889e · Cited by 21 · see citing works
Nrf2 Is Crucial to Graft Survival in a Rodent Model of Heart Transplantation
Wu, W., Qiu, Q., Wang, H., Whitman, S. A., Fang, D., Lian, F., & Zhang, D. D. (2013) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2013/919313 · Cited by 18 · see citing works
Akinrinde, A. S., Omóbòwálé, T. O., Oyagbemi, A. A., Asenuga, E. R., & Ajibade, T. O. (2016) · Canadian Journal of Physiology and Pharmacology · doi:10.1139/cjpp-2016-0197 · Cited by 18 · see citing works
Rodriguez‐Duarte, J., Galliussi, G., Dapueto, R., Rossello, J., Malacrida, L. S., Kamaid, A., Schopfer, F. J., Escande, C., López, G. V., & Batthyány, C. (2018) · British Journal of Pharmacology · doi:10.1111/bph.14561 · Cited by 16 · see citing works
Unlocking daidzein's healing power: Present applications and future possibilities in phytomedicine
Goleij, P., Sanaye, P. M., Alam, W., Zhang, J., Tabari, M. A. K., Filosa, R., Jeandet, P., Cheang, W. S., Efferth, T., & Khan, H. Z. (2024) · Phytomedicine · doi:10.1016/j.phymed.2024.155949 · Cited by 17 · see citing works
La voie Nrf2 en pathologie respiratoire
Boutten, A., Goven, D., Artaud-Macari, É., & Bonay, M. (2011) · médecine/sciences · doi:10.1051/medsci/20112711012 · Cited by 17 · see citing works
- Authors
- Mann, G. E., Bonacasa, B., Ishii, T., & Siow, R. C.
- Affiliations
- King's College London (GB)
- University of Tsukuba (JP)
- Corresponding author
- Mann, Giovanni E
- Venue
- Current Opinion in Pharmacology
- Publisher
- Elsevier BV
- Published
- 2009-04
- Volume
- 9
- Issue
- 2
- Pages
- 139-145
- ISSN
- 1471-4892 (ISSN-L)
- OpenAlex
- W2030386807
- Cited by
- 158
- References
- 78
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 5 · 2023: 8 · 2022: 3 · 2021: 7 · 2020: 9 · 2019: 8 · 2018: 5 · 2017: 6 · 2016: 18 · 2015: 13 · 2014: 11 · 2013: 8 · 2012: 11
- FWCI
- 1.33
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Current Opinion in Pharmacology (publishedVersion)
- PubMed (publishedVersion)
- Research Portal (King's College London) (submittedVersion)
- Funders
- British Heart Foundation (FS/07/020, PG/07/006/22212)
- Heart Research UK
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics, phytochemicals, and oxidative stress
- Health Sciences › Medicine › Pathology and Forensic Medicine › Phytoestrogen effects and research
- Health Sciences › Medicine › Biochemistry › Phytochemicals and Antioxidant Activities
- Keywords
- Nrf2/Keap1 pathway, isoflavones, soy isoflavones, genistein, daidzein, equol, phytoestrogens, cardiovascular disease, oxidative stress, reactive oxygen species, endothelial nitric oxide synthase, nitric oxide bioavailability, endothelial function, antioxidant gene expression, dietary supplementation
- MeSH terms
- Kelch-Like ECH-Associated Protein 1, Animals, Antioxidants, Cardiovascular Diseases, Clinical Trials as Topic, Endothelium, Vascular, Humans, Isoflavones, Models, Biological, Signal Transduction, Drug Delivery Systems, Oxidants, Reactive Oxygen Species, Nitric Oxide Synthase, Soy Foods, Intracellular Signaling Peptides and Proteins, NF-E2-Related Factor 2
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