Generic placeholder image

Current Pharmaceutical Design


ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Review Article

Impact of Antioxidant Natural Compounds on the Thyroid Gland and Implication of the Keap1/Nrf2 Signaling Pathway

Author(s): Ana Paunkov, Dionysios V. Chartoumpekis, Panos G. Ziros, Niki Chondrogianni, Thomas W. Kensler and Gerasimos P. Sykiotis*

Volume 25, Issue 16, 2019

Page: [1828 - 1846] Pages: 19

DOI: 10.2174/1381612825666190701165821

open access plus


Background: Natural compounds with potential antioxidant properties have been used in the form of food supplements or extracts with the intent to prevent or treat various diseases. Many of these compounds can activate the cytoprotective Nrf2 pathway. Besides, some of them are known to impact the thyroid gland, often with potential side-effects, but in other instances, with potential utility in the treatment of thyroid disorders.

Objective: In view of recent data regarding the multiple roles of Nrf2 in the thyroid, this review summarizes the current bibliography on natural compounds that can have an effect on thyroid gland physiology and pathophysiology, and it discusses the potential implication of the Nrf2 system in the respective mechanisms.

Methods & Results: Literature searches for articles from 1950 to 2018 were performed in PubMed and Google Scholar using relevant keywords about phytochemicals, Nrf2 and thyroid. Natural substances were categorized into phenolic compounds, sulfur-containing compounds, quinones, terpenoids, or under the general category of plant extracts. For individual compounds in each category, respective data were summarized, as derived from in vitro (cell lines), preclinical (animal models) and clinical studies. The main emerging themes were as follows: phenolic compounds often showed potential to affect the production of thyroid hormones; sulfur-containing compounds impacted the pathogenesis of goiter and the proliferation of thyroid cancer cells; while quinones and terpenoids modified Nrf2 signaling in thyroid cell lines.

Conclusion: Natural compounds that modify the activity of the Nrf2 pathway should be evaluated carefully, not only for their potential to be used as therapeutic agents for thyroid disorders, but also for their thyroidal safety when used for the prevention and treatment of non-thyroidal diseases.

Keywords: Personalized nutrition, phytochemical, flavonoid, Nrf2, thyroid, goiter, hyperthyroidism, hypothyroidism.

Hines E. New nutritive substances: Beyond the ABCs. Food Quality 1999; 6: 39-43.
Willett WC. Diet, nutrition, and avoidable cancer. Environ Health Perspect 1995; 103(Suppl. 8): 165-70.
[PMID: 8741778]
Temple NJ. Antioxidants and disease: More questions than answers. Nutr Res 2000; 20: 449-59.
Willett WC. Diet and health: What should we eat? Science 1994; 264(5158): 532-7.
[] [PMID: 8160011]
Liu RH. Health benefits of fruit and vegetables are from additive and synergistic combinaions of phytochemicals. Am J Clin Nutr 2003; 78: 3-6.
Dinkova-Kostova AT, Talalay P. Direct and indirect antioxidant properties of inducers of cytoprotective proteins. Mol Nutr Food Res 2008; 52(Suppl. 1): S128-38.
[] [PMID: 18327872]
Skibola CF, Smith MT. Potential health impacts of excessive flavonoid intake. Free Radic Biol Med 2000; 29(3-4): 375-83.
[] [PMID: 11035267]
Sykiotis GP, Bohmann D. Stress-activated cap’n’collar transcription factors in aging and human disease. Sci Signal 2010; 3(112): re3.
[] [PMID: 20215646]
Yamamoto M, Kensler TW, Motohashi H. The KEAP1-NRF2 system: A thiol-based sensor-effector apparatus for maintaining redox homeostasis. Physiol Rev 2018; 98(3): 1169-203.
[] [PMID: 29717933]
Suzuki T, Yamamoto M. Molecular basis of the Keap1-Nrf2 system. Free Radic Biol Med 2015; 88(Pt B): 93-100.
[] [PMID: 26117331]
Yamamoto T, Suzuki T, Kobayashi A, et al. Physiological significance of reactive cysteine residues of Keap1 in determining Nrf2 activity. Mol Cell Biol 2008; 28(8): 2758-70.
[] [PMID: 18268004]
Kwak MK, Wakabayashi N, Greenlaw JL, Yamamoto M, Kensler TW. Antioxidants enhance mammalian proteasome expression through the Keap1-Nrf2 signaling pathway. Mol Cell Biol 2003; 23(23): 8786-94.
[] [PMID: 14612418]
Saito R, Suzuki T, Hiramoto K, et al. Characterizations of Three Major Cysteine Sensors of Keap1 in Stress Response. Mol Cell Biol 2015; 36(2): 271-84.
[] [PMID: 26527616]
Zhang Y, Talalay P, Cho CG, Posner GH. A major inducer of anticarcinogenic protective enzymes from broccoli: Isolation and elucidation of structure. Proc Natl Acad Sci USA 1992; 89(6): 2399-403.
[] [PMID: 1549603]
Dinkova-Kostova AT, Holtzclaw WD, Cole RN, et al. Direct evidence that sulfhydryl groups of Keap1 are the sensors regulating induction of phase 2 enzymes that protect against carcinogens and oxidants. Proc Natl Acad Sci USA 2002; 99(18): 11908-13.
[] [PMID: 12193649]
Egner PA, Chen JG, Wang JB, et al. Bioavailability of Sulforaphane from two broccoli sprout beverages: Results of a short-term, cross-over clinical trial in Qidong, China. Cancer Prev Res (Phila) 2011; 4(3): 384-95.
[] [PMID: 21372038]
Dinkova-Kostova AT, Fahey JW, Kostov RV, Kensler TW. KEAP1 and Done? Targeting the NRF2 Pathway with Sulforaphane. Trends Food Sci Technol. 2017; 69(Pt B): 257-69.
[] [PMID: 29242678]
Kensler TW, Ng D, Carmella SG, et al. Modulation of the metabolism of airborne pollutants by glucoraphanin-rich and sulforaphane-rich broccoli sprout beverages in Qidong, China. Carcinogenesis 2012; 33(1): 101-7.
[] [PMID: 22045030]
Axelsson AS, Tubbs E, Mecham B, et al. Sulforaphane reduces hepatic glucose production and improves glucose control in patients with type 2 diabetes. Sci Transl Med 2017; 9(394): 9.
[] [PMID: 28615356]
Singh K, Connors SL, Macklin EA, et al. Sulforaphane treatment of autism spectrum disorder (ASD). Proc Natl Acad Sci USA 2014; 111(43): 15550-5.
[] [PMID: 25313065]
Surh YJ, Kundu JK, Na HK. Nrf2 as a master redox switch in turning on the cellular signaling involved in the induction of cytoprotective genes by some chemopreventive phytochemicals. Planta Med 2008; 74(13): 1526-39.
[] [PMID: 18937164]
Chaker L, Bianco AC, Jonklaas J, Peeters RP. Hypothyroidism. Lancet 2017; 390(10101): 1550-62.
[] [PMID: 28336049]
Hollowell JG. academic.oup.comNWSJoC, undefined. Serum TSH, T4, and Thyroid Antibodies in the United States Population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III)..
McLeod DSA, Cooper DS. The incidence and prevalence of thyroid autoimmunity. Endocrine 2012; 42(2): 252-65.
[] [PMID: 22644837]
Faggiano A, Del Prete M, Marciello F, Marotta V, Ramundo V, Colao A. Thyroid diseases in elderly. Minerva Endocrinol 2011; 36(3): 211-31.
[PMID: 22019751]
Tabatabaie V, Surks MI. The aging thyroid. Curr Opin Endocrinol Diabetes Obes 2013; 20(5): 455-9.
[] [PMID: 23974775]
Hurley DL, Gharib H. Evaluation and management of multinodular goiter. Otolaryngol Clin North Am 1996; 29(4): 527-40.
[PMID: 8844728]
Divi RL, Doerge DR. Mechanism-based inactivation of lactoperoxidase and thyroid peroxidase by resorcinol derivatives. Biochemistry 1994; 33(32): 9668-74.
[] [PMID: 8068644]
Gaitan E. Flavonoids and the thyroid. Nutrition 1996; 12(2): 127-9.
[] [PMID: 8724387]
Kopp P. Thyroid hormone synthesis.In: Braverman LE, Utiger RD, ed.^eds. Lippincott Williams & Wilkins: Philadelphia, USA, 2005; 48-74.
Carvalho DP, Dupuy C. Thyroid hormone biosynthesis and release. Mol Cell Endocrinol 2017; 458: 6-15.
[] [PMID: 28153798]
Scott DA, Wang R, Kreman TM, Sheffield VC, Karniski LP. The Pendred syndrome gene encodes a chloride-iodide transport protein. Nat Genet 1999; 21(4): 440-3.
[] [PMID: 10192399]
Gillam MP, Sidhaye AR, Lee EJ, Rutishauser J, Stephan CW, Kopp P. Functional characterization of pendrin in a polarized cell system. Evidence for pendrin-mediated apical iodide efflux. J Biol Chem 2004; 279(13): 13004-10.
[] [PMID: 14715652]
Silveira JC, Kopp PA. Pendrin and anoctamin as mediators of apical iodide efflux in thyroid cells. Curr Opin Endocrinol Diabetes Obes 2015; 22(5): 374-80.
[] [PMID: 26313899]
Massart C, Hoste C, Virion A, Ruf J, Dumont JE, Van Sande J. Cell biology of H2O2 generation in the thyroid: Investigation of the control of dual oxidases (DUOX) activity in intact ex vivo thyroid tissue and cell lines. Mol Cell Endocrinol 2011; 343(1-2): 32-44.
[] [PMID: 21683758]
Rousset B, Dupuy C, Miot F, Dumont J. Chapter 2 Thyroid Hormone Synthesis And Secretion., Inc. 2000.
Dunn AD, Crutchfield HE, Dunn JT. Proteolytic processing of thyroglobulin by extracts of thyroid lysosomes. Endocrinology 1991; 128(6): 3073-80.
[] [PMID: 1903699]
Dunn AD, Crutchfield HE, Dunn JT. Thyroglobulin processing by thyroidal proteases. Major sites of cleavage by cathepsins B, D, and L. J Biol Chem 1991; 266(30): 20198-204.
[PMID: 1939080]
Gnidehou S, Caillou B, Talbot M, et al. Iodotyrosine dehalogenase 1 (DEHAL1) is a transmembrane protein involved in the recycling of iodide close to the thyroglobulin iodination site. FASEB J 2004; 18(13): 1574-6.
[] [PMID: 15289438]
Poncin S, Colin IM, Gérard AC. Minimal oxidative load: A prerequisite for thyroid cell function. J Endocrinol 2009; 201(1): 161-7.
[] [PMID: 19168506]
Poncin S, Eeckoudt SV, Humblet K. IMCTAjo, undefined.Oxidative stress: A required condition for thyroid cell proliferation. Elsevier.
Poncin S, Gerard AC, Boucquey M. IMCTAjo, undefined.Oxidative stress: A required condition for thyroid cell proliferation. Elsevier
Ziros PG, Habeos IG, Chartoumpekis DV, et al. NFE2-related transcription factor 2 coordinates antioxidant defense with thyroglobulin production and iodination in the thyroid gland. Thyroid 2018; 28(6): 780-98.
[] [PMID: 29742982]
Maier J, van Steeg H, van Oostrom C, Paschke R, Weiss RE, Krohn K. Iodine deficiency activates antioxidant genes and causes DNA damage in the thyroid gland of rats and mice. Biochim Biophys Acta 2007; 1773(6): 990-9.
[] [PMID: 17467074]
Krohn K, Maier J, Paschke R. Mechanisms of disease: Hydrogen peroxide, DNA damage and mutagenesis in the development of thyroid tumors. Nat Clin Pract Endocrinol Metab 2007; 3(10): 713-20.
[] [PMID: 17893690]
Leoni SG, Kimura ET, Santisteban P, De la Vieja A. Regulation of thyroid oxidative state by thioredoxin reductase has a crucial role in thyroid responses to iodide excess. Mol Endocrinol 2011; 25(11): 1924-35.
[] [PMID: 21903721]
Poncin S, Gérard A-C, Boucquey M, et al. Oxidative stress in the thyroid gland: From harmlessness to hazard depending on the iodine content. Endocrinology 2008; 149(1): 424-33.
[] [PMID: 17884933]
Di Jeso B, Arvan P. Thyroglobulin from molecular and cellular biology to clinical endocrinology. Endocr Rev 2016; 37(1): 2-36.
[] [PMID: 26595189]
Leonard JL, Korhle J. Intracellular pathways of iodothyronine metabolism.The Thyroid-A Funda-mental and Clinical Text, seventh ed. Philadelphia, USA 1996.
Wakabayashi N, Chartoumpekis DV, Kensler TW. Crosstalk between Nrf2 and Notch signaling. Free Radic Biol Med 2015; 88(pt B): 158-67.
[] [PMID: 26003520]
Chartoumpekis DV, Kensler TW. New player on an old field; the keap1/Nrf2 pathway as a target for treatment of type 2 diabetes and metabolic syndrome. Curr Diabetes Rev 2013; 9(2): 137-45.
[] [PMID: 23363332]
Sellitti DF, Suzuki K. Intrinsic regulation of thyroid function by thyroglobulin. Thyroid 2014; 24(4): 625-38.
[] [PMID: 24251883]
Ferrandino G, Kaspari RR, Reyna-Neyra A, Boutagy NE, Sinusas AJ, Carrasco N. An extremely high dietary iodide supply forestalls severe hypothyroidism in Na+/I- symporter (NIS) knockout mice. Sci Rep 2017; 7(1): 5329.
[] [PMID: 28706256]
Rossich LE, Thomasz L, Nicola JP, et al. Effects of 2-iodohexadecanal in the physiology of thyroid cells. Mol Cell Endocrinol 2016; 437: 292-301.
[] [PMID: 27568464]
Ziros PG, Manolakou SD, Habeos IG, et al. Nrf2 is commonly activated in papillary thyroid carcinoma, and it controls antioxidant transcriptional responses and viability of cancer cells. J Clin Endocrinol Metab 2013; 98(8): E1422-7.
[] [PMID: 23766517]
Martinez VD, Vucic EA, Pikor LA, Thu KL, Hubaux R, Lam WL. Frequent concerted genetic mechanisms disrupt multiple components of the NRF2 inhibitor KEAP1/CUL3/RBX1 E3-ubiquitin ligase complex in thyroid cancer. Mol Cancer 2013; 12(1): 124.
[] [PMID: 24138990]
Crozier A, Clifford MN, Ashihara H. Plant Secondary Metabolites: Occurrence. Structure and Role in the Human Diet 2007.
Gould KS. Nature’s Swiss Army Knife: The Diverse Protective Roles of Anthocyanins in Leaves. J Biomed Biotechnol 2004; 2004(5): 314-20.
[] [PMID: 15577195]
Dewick PM. Medicinal natural products: A biosynthetic approach. Medicinal natural products: A bi-osynthetic approach. 1997.
Croteau R. KTMLNG. Natural products (secondary metabolites) 2000.
Bravo L. Polyphenols: Chemistry, dietary sources, metabolism, and nutritional significance. Nutr Rev 1998; 56(11): 317-33.
[] [PMID: 9838798]
Han X, Shen T, Lou H, Han X, Shen T, Lou H. Dietary Polyphenols and Their Biological Significance. Int J Mol Sci 2007; 8: 950-88.
Moudgal NR, Raghupathy E, Sarma PS. Studies on goitrogenic agents in food. III. Goitrogenic action of some glycosides isolated from edible nuts. J Nutr 1958; 66(2): 291-303.
[] [PMID: 13599069]
Cai Y, Luo Q, Sun M, Corke H. Antioxidant activity and phenolic compounds of 112 traditional Chinese medicinal plants associated with anticancer. Life Sci 2004; 74(17): 2157-84.
[] [PMID: 14969719]
Divi RL, Doerge DR. Inhibition of thyroid peroxidase by dietary flavonoids. Chem Res Toxicol 1996; 9(1): 16-23.
[] [PMID: 8924586]
Yin F, Giuliano AE, Van Herle AJ. Growth inhibitory effects of flavonoids in human thyroid cancer cell lines. Thyroid 1999; 9(4): 369-76.
[] [PMID: 10319943]
Schröder-van der Elst JP, Smit JWA, Romijn HA, van der Heide D. Dietary flavonoids and iodine metabolism. Biofactors 2003; 19(3-4): 171-6.
[] [PMID: 14757968]
Gaitan E, Lindsay RH, Reichert RD, et al. Antithyroid and goitrogenic effects of millet: Role of C-glycosylflavones. J Clin Endocrinol Metab 1989; 68(4): 707-14.
[] [PMID: 2921306]
Ferreira ACF, Lisboa PC, Oliveira KJ, Lima LP, Barros IA, Carvalho DP. Inhibition of thyroid type 1 deiodinase activity by flavonoids. Food Chem Toxicol 2002; 40(7): 913-7.
[] [PMID: 12065212]
Park CH, Han SE, Nam-goong IS, Kim YI, Kim ES. Combined effects of baicalein and docetaxel on apoptosis in 8505c anaplastic thyroid cancer cells via downregulation of the ERK and Akt/mTOR pathways. Endocrin Metab 2018; 33(1): 121-32.
Gaique TG, Lopes BP, Souza LL, Paula GSM, Pazos-Moura CC, Oliveira KJ. Cinnamon intake reduces serum T3 level and modulates tissue-specific expression of thyroid hormone receptor and target genes in rats. J Sci Food Agric 2016; 96(8): 2889-95.
[] [PMID: 26374392]
Nabavi SF, Moghaddam AH, Nabavi SM, Eslami S. Protective effect of curcumin and quercetin on thyroid function in sodium fluoride intoxicated rats. Fluoride 2011; 44: 147-52.
Allegri L, Rosignolo F, Mio C, Filetti S, Baldan F, Damante G. Effects of nutraceuticals on anaplastic thyroid cancer cells. J Cancer Res Clin Oncol 2018; 144(2): 285-94.
[] [PMID: 29197967]
Sosić-Jurjević B, Filipović B, Ajdzanović V, et al. Suppressive effects of genistein and daidzein on pituitary-thyroid axis in orchidectomized middle-aged rats. Exp Biol Med (Maywood) 2010; 235(5): 590-8.
[] [PMID: 20463299]
Dodurga Y, Eroğlu C, Seçme M, Elmas L, Avcı ÇB, Şatıroğlu-Tufan NL. Anti-proliferative and anti-invasive effects of ferulic acid in TT medullary thyroid cancer cells interacting with URG4/URGCP. Tumour Biol 2016; 37(2): 1933-40.
[] [PMID: 26334619]
Kang HJ, Youn YK, Hong MK, Kim LS. Antiproliferation and redifferentiation in thyroid cancer cell lines by polyphenol phytochemicals. J Korean Med Sci 2011; 26(7): 893-9.
[] [PMID: 21738342]
Divi RL, Chang HC, Doerge DR. Anti-thyroid isoflavones from soybean: Isolation, characterization, and mechanisms of action. Biochem Pharmacol 1997; 54(10): 1087-96.
[] [PMID: 9464451]
Miler M, Jarić I, Živanović J, et al. Citrus flavanones mildly interfere with pituitary-thyroid axis in old-aged male rats. Acta Histochem 2017; 119(3): 292-301.
[] [PMID: 28262328]
Ferreira ACF, Neto JC, da Silva ACM, Kuster RM, Carvalho DP. Inhibition of thyroid peroxidase by Myrcia uniflora flavonoids. Chem Res Toxicol 2006; 19(3): 351-5.
[] [PMID: 16544938]
Jo S, Ha TK, Han SH, et al. Myricetin Induces Apoptosis of Human Anaplastic Thyroid Cancer Cells via Mitochondria Dysfunction. Anticancer Res 2017; 37(4): 1705-10.
[] [PMID: 28373432]
Gaitan E. Environmental Goitrogenesis. In: Ed, 1989; 52.
Chung HJ, Chung MJ, Houng SJ, et al. Toxicological evaluation of the isoflavone puerarin and its glycosides. Eur Food Res Technol 2009; 230: 145-53.
Giuliani C, Bucci I, Di Santo S, et al. The flavonoid quercetin inhibits thyroid-restricted genes expression and thyroid function. Food Chem Toxicol 2014; 66: 23-9.
[] [PMID: 24447974]
Giuliani C, Noguchi Y, Harii N, et al. The flavonoid quercetin regulates growth and gene expression in rat FRTL-5 thyroid cells. Endocrinology 2008; 149(1): 84-92.
[] [PMID: 17962351]
Sebai H, Hovsépian S, Ristorcelli E, Aouani E, Lombardo D, Fayet G. Resveratrol increases iodide trapping in the rat thyroid cell line FRTL-5. Thyroid 2010; 20(2): 195-203.
[] [PMID: 20151827]
Shih A, Davis FB, Lin H-Y, Davis PJ. Resveratrol induces apoptosis in thyroid cancer cell lines via a MAPK- and p53-dependent mechanism. J Clin Endocrinol Metab 2002; 87(3): 1223-32.
[] [PMID: 11889192]
Lin CJ, Lin CY, Chen Y, Huang SH, Wang SM. Rottlerin inhibits migration of follicular thyroid carcinoma cells by PKCdelta-independent destabilization of the focal adhesion complex. J Cell Biochem 2010; 110(2): 428-37.
[PMID: 20225271]
Jatwa R, Kar A, Pradesh M. Protective Effect of L-Ornithine-L-Aspartate and Silymarin on Chemically Induced Kidney Toxicity and thyroid dysfunction in mice. EXCLI J 2008; 7: 139-50.
Radović B, Schmutzler C, Köhrle J. Xanthohumol stimulates iodide uptake in rat thyroid-derived FRTL-5 cells. Mol Nutr Food Res 2005; 49(9): 832-6.
[] [PMID: 16092068]
Renko K, Schäche S, Hoefig CS, et al. An Improved Nonradioactive Screening Method Identifies Genistein and Xanthohumol as Potent Inhibitors of Iodothyronine Deiodinases. Thyroid 2015; 25(8): 962-8.
[] [PMID: 25962824]
Leonard J, Koehrle J. Intracellular pathways of iodothyronine metabolism. In: Braverman L, Utiger R, ed Philadelphia, USA. 1996; 136-73.
Huang WY, Cai YZ, Zhang Y. Natural phenolic compounds from medicinal herbs and dietary plants: Potential use for cancer prevention. Nutr Cancer 2010; 62(1): 1-20.
[] [PMID: 20043255]
Middleton E Jr, Kandaswami C, Theoharides TC, Kandaswami C, Theoharides TC, Theoharides TC. The effects of plant flavonoids on mammalian cells: Implications for inflammation, heart disease, and cancer. Pharmacol Rev 2000; 52(4): 673-751.
[PMID: 11121513]
Izumi Y, Matsumura A, Wakita S, et al. Isolation, identification, and biological evaluation of Nrf2-ARE activator from the leaves of green perilla (Perilla frutescens var. crispa f. viridis). Free Radic Biol Med 2012; 53(4): 669-79.
[] [PMID: 22749808]
Lee D-S, Li B. Im N-K, Kim Y-C, Jeong G-S. 4,2′,5′-Trihydroxy-4′-methoxychalcone from Dalbergia odorifera exhibits anti-inflammatory properties by inducing heme oxygenase-1 in murine macrophages. Int Immunopharmacol 2013; 16: 114-21.
[] [PMID: 23566812]
Paredes-Gonzalez X, Fuentes F, Jeffery S, et al. Induction of NRF2-mediated gene expression by dietary phytochemical flavones apigenin and luteolin. Biopharm Drug Dispos 2015; 36(7): 440-51.
[] [PMID: 25904312]
Huang CS, Lii CK, Lin AH, et al. Protection by chrysin, apigenin, and luteolin against oxidative stress is mediated by the Nrf2-dependent up-regulation of heme oxygenase 1 and glutamate cysteine ligase in rat primary hepatocytes. Arch Toxicol 2013; 87(1): 167-78.
[] [PMID: 22864849]
Gao AM, Ke ZP, Wang JN, Yang JY, Chen SY, Chen H. Apigenin sensitizes doxorubicin-resistant hepatocellular carcinoma BEL-7402/ADM cells to doxorubicin via inhibiting PI3K/Akt/Nrf2 pathway. Carcinogenesis 2013; 34(8): 1806-14.
[] [PMID: 23563091]
Lee C-Y, Chew E-H, Go M-L. Functionalized aurones as inducers of NAD(P)H:quinone oxidoreductase 1 that activate AhR/XRE and Nrf2/ARE signaling pathways: Synthesis, evaluation and SAR. Eur J Med Chem 2010; 45(7): 2957-71.
[] [PMID: 20392544]
Zhang Z, Cui W, Li G, et al. Baicalein protects against 6-OHDA-induced neurotoxicity through activation of Keap1/Nrf2/HO-1 and involving PKCα and PI3K/AKT signaling pathways. J Agric Food Chem 2012; 60(33): 8171-82.
[] [PMID: 22838648]
Liu X, Wang T, Liu X, et al. Biochanin A protects lipopolysaccharide/D-galactosamine-induced acute liver injury in mice by activating the Nrf2 pathway and inhibiting NLRP3 inflammasome activation. Int Immunopharmacol 2016; 38: 324-31.
[] [PMID: 27344638]
Choi B-M, Kim B-R. Upregulation of heme oxygenase-1 by brazilin via the phosphatidylinositol 3-kinase/Akt and ERK pathways and its protective effect against oxidative injury. Eur J Pharmacol 2008; 580(1-2): 12-8.
[] [PMID: 18021765]
Liang L, Luo M, Fu Y, et al. Cajaninstilbene acid (CSA) exerts cytoprotective effects against oxidative stress through the Nrf2-dependent antioxidant pathway. Toxicol Lett 2013; 219(3): 254-61.
[] [PMID: 23535287]
Huang T-C, Chung Y-L, Wu M-L, Chuang S-M. Cinnamaldehyde enhances Nrf2 nuclear translocation to upregulate phase II detoxifying enzyme expression in HepG2 cells. J Agric Food Chem 2011; 59(9): 5164-71.
[] [PMID: 21469739]
Kang ES, Woo IS, Kim HJ, et al. Up-regulation of aldose reductase expression mediated by phosphatidylinositol 3-kinase/Akt and Nrf2 is involved in the protective effect of curcumin against oxidative damage. Free Radic Biol Med 2007; 43(4): 535-45.
[] [PMID: 17640564]
Shen G, Xu C, Hu R, et al. Modulation of nuclear factor E2-related factor 2-mediated gene expression in mice liver and small intestine by cancer chemopreventive agent curcumin. Mol Cancer Ther 2006; 5(1): 39-51.
[] [PMID: 16432161]
Balogun E, Hoque M, Gong P, et al. Curcumin activates the haem oxygenase-1 gene via regulation of Nrf2 and the antioxidant-responsive element. Biochem J 2003; 371(Pt 3): 887-95.
[] [PMID: 12570874]
Chapple SJ, Siow RCM, Mann GE. Crosstalk between Nrf2 and the proteasome: Therapeutic potential of Nrf2 inducers in vascular disease and aging. Int J Biochem Cell Biol 2012; 44(8): 1315-20.
[] [PMID: 22575091]
Chong CM, Zhou ZY, Razmovski-Naumovski V, et al. Danshensu protects against 6-hydroxydopamine-induced damage of PC12 cells in vitro and dopaminergic neurons in zebrafish. Neurosci Lett 2013; 543: 121-5.
[] [PMID: 23562886]
Kim HJ, Lim SS, Park IS, Lim JS, Seo JY, Kim J-S. Neuroprotective effects of dehydroglyasperin C through activation of heme oxygenase-1 in mouse hippocampal cells. J Agric Food Chem 2012; 60(22): 5583-9.
[] [PMID: 22578244]
Lee SE, Yang H, Son GW, et al. Eriodictyol protects endothelial cells against oxidative stress-induced cell death through modulating ERK/Nrf2/ARE-dependent heme oxygenase-1 expression. Int J Mol Sci 2015; 16(7): 14526-39.
[] [PMID: 26132561]
Lou H, Jing X, Ren D, Wei X, Zhang X. Eriodictyol protects against H(2)O(2)-induced neuron-like PC12 cell death through activation of Nrf2/ARE signaling pathway. Neurochem Int 2012; 61(2): 251-7.
[] [PMID: 22609376]
Hu Q, Zhang DD, Wang L, Lou H, Ren D. Eriodictyol-7-O-glucoside, a novel Nrf2 activator, confers protection against cisplatin-induced toxicity. Food Chem Toxicol 2012; 50(6): 1927-32.
[] [PMID: 22465804]
Song HJ, Shin CY, Oh TY, Sohn UD. The protective effect of eupatilin on indomethacin-induced cell damage in cultured feline ileal smooth muscle cells: Involvement of HO-1 and ERK. J Ethnopharmacol 2008; 118(1): 94-101.
[] [PMID: 18440740]
Ma Z-C, Hong Q, Wang Y-G, et al. Ferulic acid protects human umbilical vein endothelial cells from radiation induced oxidative stress by phosphatidylinositol 3-kinase and extracellular signal-regulated kinase pathways. Biol Pharm Bull 2010; 33(1): 29-34.
[] [PMID: 20045931]
Lee SE, Jeong SI, Yang H, Park C-S, Jin Y-H, Park YS. Fisetin induces Nrf2-mediated HO-1 expression through PKC-δ and p38 in human umbilical vein endothelial cells. J Cell Biochem 2011; 112(9): 2352-60.
[] [PMID: 21520244]
Zhao X, Zou Y, Xu H, et al. Gastrodin protect primary cultured rat hippocampal neurons against amyloid-beta peptide-induced neurotoxicity via ERK1/2-Nrf2 pathway. Brain Res 2012; 1482: 13-21.
[] [PMID: 22982592]
Ma W, Yuan L, Yu H, et al. Genistein as a neuroprotective antioxidant attenuates redox imbalance induced by β-amyloid peptides 25-35 in PC12 cells. Int J Dev Neurosci 2010; 28(4): 289-95.
[] [PMID: 20362658]
Wiegand H, Wagner AE, Boesch-Saadatmandi C, Kruse H-P, Kulling S, Rimbach G. Effect of dietary genistein on Phase II and antioxidant enzymes in rat liver. Cancer Genomics Proteomics 2009; 6(2): 85-92.
[PMID: 19451092]
Zhang T, Wang F, Xu H-X, et al. Activation of nuclear factor erythroid 2-related factor 2 and PPARγ plays a role in the genistein-mediated attenuation of oxidative stress-induced endothelial cell injury. Br J Nutr 2013; 109(2): 223-35.
[] [PMID: 22716961]
Zhu C, Dong Y, Liu H, Ren H, Cui Z. Hesperetin protects against H2O2-triggered oxidative damage via upregulation of the Keap1-Nrf2/HO-1 signal pathway in ARPE-19 cells. Biomed Pharmacother 2017; 88: 124-33.
[] [PMID: 28103505]
Elavarasan J, Velusamy P, Ganesan T, Ramakrishnan SK, Rajasekaran D, Periandavan K. Hesperidin-mediated expression of Nrf2 and upregulation of antioxidant status in senescent rat heart. J Pharm Pharmacol 2012; 64(10): 1472-82.
[] [PMID: 22943178]
Gu J, Sun X, Wang G, Li M, Chi M. Icariside II enhances Nrf2 nuclear translocation to upregulate phase II detoxifying enzyme expression coupled with the ERK, Akt and JNK signaling pathways. Molecules 2011; 16(11): 9234-44.
[] [PMID: 22051934]
Lim JH, Park H-S, Choi J-K, Lee I-S, Choi HJ. Isoorientin induces Nrf2 pathway-driven antioxidant response through phosphatidylinositol 3-kinase signaling. Arch Pharm Res 2007; 30(12): 1590-8.
[] [PMID: 18254247]
Saw CLL, Guo Y, Yang AY, et al. The berry constituents quercetin, kaempferol, and pterostilbene synergistically attenuate reactive oxygen species: Involvement of the Nrf2-ARE signaling pathway. Food Chem Toxicol 2014; 72: 303-11.
[] [PMID: 25111660]
Gao SS, Choi B-M, Chen XY, et al. Kaempferol suppresses cisplatin-induced apoptosis via inductions of heme oxygenase-1 and glutamate-cysteine ligase catalytic subunit in HEI-OC1 cell. Pharm Res 2010; 27(2): 235-45.
[] [PMID: 19937094]
Hirose E, Matsushima M, Takagi K, et al. Involvement of heme oxygenase-1 in kaempferol-induced anti-allergic actions in RBL-2H3 cells. Inflammation 2009; 32(2): 99-108.
[] [PMID: 19214725]
Lee BW, Chun SW, Kim SH, et al. Lithospermic acid B protects β-cells from cytokine-induced apoptosis by alleviating apoptotic pathways and activating anti-apoptotic pathways of Nrf2-HO-1 and Sirt1. Toxicol Appl Pharmacol 2011; 252(1): 47-54.
[] [PMID: 21295052]
Chen W-C, Wang S-Y, Chiu C-C, et al. Lucidone suppresses hepatitis C virus replication by Nrf2-mediated heme oxygenase-1 induction. Antimicrob Agents Chemother 2013; 57(3): 1180-91.
[] [PMID: 23254429]
Kumar KJ, Yang HL, Tsai YC, et al. Lucidone protects human skin keratinocytes against free radical-induced oxidative damage and inflammation through the up-regulation of HO-1/Nrf2 antioxidant genes and down-regulation of NF-κB signaling pathway. Food Chem Toxicol 2013; 59: 55-66.
[] [PMID: 23712098]
Tang X, Wang H, Fan L, et al. Luteolin inhibits Nrf2 leading to negative regulation of the Nrf2/ARE pathway and sensitization of human lung carcinoma A549 cells to therapeutic drugs. Free Radic Biol Med 2011; 50(11): 1599-609.
[] [PMID: 21402146]
Chian S, Thapa R, Chi Z, Wang XJ, Tang X. Luteolin inhibits the Nrf2 signaling pathway and tumor growth in vivo. Biochem Biophys Res Commun 2014; 447(4): 602-8.
[] [PMID: 24747074]
Lee MH, Han MH, Lee DS, et al. Morin exerts cytoprotective effects against oxidative stress in C2C12 myoblasts via the upregulation of Nrf2-dependent HO-1 expression and the activation of the ERK pathway. Int J Mol Med 2017; 39(2): 399-406.
[] [PMID: 28035409]
Cho BO, Yin HH, Park SH, Byun EB, Ha HY, Jang SI. Anti-inflammatory activity of myricetin from Diospyros lotus through suppression of NF-κB and STAT1 activation and Nrf2-mediated HO-1 induction in lipopolysaccharide-stimulated RAW264.7 macrophages. Biosci Biotechnol Biochem 2016; 80(8): 1520-30.
[] [PMID: 27068250]
Zhang B, Chen Y, Shen Q, et al. Myricitrin attenuates high glucose-induced apoptosis through activating Akt-Nrf2 signaling in H9c2 cardiomyocytes. Molecules 2016; 21(7): 1-13.
[] [PMID: 27399653]
Ramprasath T, Senthamizharasi M, Vasudevan V, Sasikumar S, Yuvaraj S, Selvam GS. Naringenin confers protection against oxidative stress through upregulation of Nrf2 target genes in cardiomyoblast cells. J Physiol Biochem 2014; 70(2): 407-15.
[] [PMID: 24526395]
Lou H, Jing X, Wei X, Shi H, Ren D, Zhang X. Naringenin protects against 6-OHDA-induced neurotoxicity via activation of the Nrf2/ARE signaling pathway. Neuropharmacology 2014; 79: 380-8.
[] [PMID: 24333330]
Esmaeili MA, Alilou M. Naringenin attenuates CCl4 -induced hepatic inflammation by the activation of an Nrf2-mediated pathway in rats. Clin Exp Pharmacol Physiol 2014; 41(6): 416-22.
[] [PMID: 24684352]
Kil J-S, Son Y, Cheong Y-K, et al. Okanin, a chalcone found in the genus Bidens, and 3-penten-2-one inhibit inducible nitric oxide synthase expression via heme oxygenase-1 induction in RAW264.7 macrophages activated with lipopolysaccharide. J Clin Biochem Nutr 2012; 50(1): 53-8.
[] [PMID: 22247601]
Yeh CT, Ching LC, Yen GC. Inducing gene expression of cardiac antioxidant enzymes by dietary phenolic acids in rats. J Nutr Biochem 2009; 20(3): 163-71.
[] [PMID: 18547798]
Yang Y-C, Lii C-K, Lin A-H, et al. Induction of glutathione synthesis and heme oxygenase 1 by the flavonoids butein and phloretin is mediated through the ERK/Nrf2 pathway and protects against oxidative stress. Free Radic Biol Med 2011; 51(11): 2073-81.
[] [PMID: 21964506]
Ryu J, Zhang R, Hong BH, et al. Phloroglucinol attenuates motor functional deficits in an animal model of Parkinson’s disease by enhancing Nrf2 activity. PLoS One 2013; 8(8)e71178
[] [PMID: 23976995]
Lee HH, Park SA, Almazari I, Kim EH, Na HK, Surh YJ. Piceatannol induces heme oxygenase-1 expression in human mammary epithelial cells through activation of ARE-driven Nrf2 signaling. Arch Biochem Biophys 2010; 501(1): 142-50.
[] [PMID: 20558128]
Son Y, Byun SJ, Pae HO. Involvement of heme oxygenase-1 expression in neuroprotection by piceatannol, a natural analog and a metabolite of resveratrol, against glutamate-mediated oxidative injury in HT22 neuronal cells. Amino Acids 2013; 45(2): 393-401.
[] [PMID: 23712764]
Varì R, D’Archivio M, Filesi C, et al. Protocatechuic acid induces antioxidant/detoxifying enzyme expression through JNK-mediated Nrf2 activation in murine macrophages. J Nutr Biochem 2011; 22(5): 409-17.
[] [PMID: 20621462]
Hwang YP, Jeong HG. Mechanism of phytoestrogen puerarin-mediated cytoprotection following oxidative injury: Estrogen receptor-dependent up-regulation of PI3K/Akt and HO-1. Toxicol Appl Pharmacol 2008; 233(3): 371-81.
[] [PMID: 18845176]
Tanigawa S, Fujii M, Hou DX. Action of Nrf2 and Keap1 in ARE-mediated NQO1 expression by quercetin. Free Radic Biol Med 2007; 42(11): 1690-703.
[] [PMID: 17462537]
Palsamy P, Subramanian S. Resveratrol protects diabetic kidney by attenuating hyperglycemia-mediated oxidative stress and renal inflammatory cytokines via Nrf2-Keap1 signaling. Biochim Biophys Acta 2011; 1812(7): 719-31.
[] [PMID: 21439372]
Park EJ, Lim JH, Nam SI, Park JW, Kwon TK. Rottlerin induces heme oxygenase-1 (HO-1) up-regulation through reactive oxygen species (ROS) dependent and PKC δ-independent pathway in human colon cancer HT29 cells. Biochimie 2010; 92(1): 110-5.
[] [PMID: 19833168]
Tian R, Yang W, Xue Q, et al. Rutin ameliorates diabetic neuropathy by lowering plasma glucose and decreasing oxidative stress via Nrf2 signaling pathway in rats. Eur J Pharmacol 2016; 771: 84-92.
[] [PMID: 26688570]
Jeong G-S, Lee D-S, Li B, Lee H-J, Kim E-C, Kim Y-C. Effects of sappanchalcone on the cytoprotection and anti-inflammation via heme oxygenase-1 in human pulp and periodontal ligament cells. Eur J Pharmacol 2010; 644(1-3): 230-7.
[] [PMID: 20621084]
Zhao F, Shi D, Li T, Li L, Zhao M. Silymarin attenuates paraquat-induced lung injury via Nrf2-mediated pathway in vivo and in vitro. Clin Exp Pharmacol Physiol 2015; 42(9): 988-98.
[] [PMID: 26173462]
Manigandan K, Manimaran D, Jayaraj RL, Elangovan N, Dhivya V, Kaphle A. Taxifolin curbs NF-κB-mediated Wnt/β-catenin signaling via up-regulating Nrf2 pathway in experimental colon carcinogenesis. Biochimie 2015; 119: 103-12.
[] [PMID: 26482805]
Malar DS, Suryanarayanan V, Prasanth MI, Singh SK, Balamurugan K, Devi KP. Vitexin inhibits Aβ25-35 induced toxicity in Neuro-2a cells by augmenting Nrf-2/HO-1 dependent antioxidant pathway and regulating lipid homeostasis by the activation of LXR-α. Toxicol In Vitro 2018; 50: 160-71.
[] [PMID: 29545167]
Yao J, Zhang B, Ge C, Peng S, Fang J. Xanthohumol, a polyphenol chalcone present in hops, activating Nrf2 enzymes to confer protection against oxidative damage in PC12 cells. J Agric Food Chem 2015; 63(5): 1521-31.
[] [PMID: 25587858]
Lv H, Liu Q, Wen Z, Feng H, Deng X, Ci X. Xanthohumol ameliorates lipopolysaccharide (LPS)-induced acute lung injury via induction of AMPK/GSK3β-Nrf2 signal axis. Redox Biol 2017; 12: 311-24.
[] [PMID: 28285192]
Krajka-Kuźniak V, Paluszczak J, Baer-Dubowska W. Xanthohumol induces phase II enzymes via Nrf2 in human hepatocytes in vitro. Toxicol In Vitro 2013; 27(1): 149-56.
[] [PMID: 23085367]
Lee IS, Lim J, Gal J, et al. Anti-inflammatory activity of xanthohumol involves heme oxygenase-1 induction via NRF2-ARE signaling in microglial BV2 cells. Neurochem Int 2011; 58(2): 153-60.
[] [PMID: 21093515]
Tan AC, Konczak I, Sze DMY, Ramzan I. Molecular pathways for cancer chemoprevention by dietary phytochemicals. Nutr Cancer 2011; 63(4): 495-505.
[] [PMID: 21500099]
Jomova K, Vondrakova D, Lawson M, Valko M. Metals, oxidative stress and neurodegenerative disorders. Mol Cell Biochem 2010; 345(1-2): 91-104.
[] [PMID: 20730621]
Shu L, Khor TO, Lee J-H, et al. Epigenetic CpG demethylation of the promoter and reactivation of the expression of Neurog1 by curcumin in prostate LNCaP cells. AAPS J 2011; 13(4): 606-14.
[] [PMID: 21938566]
Sithisarn P, Michaelis M, Schubert-Zsilavecz M, Cinatl J Jr. Differential antiviral and anti-inflammatory mechanisms of the flavonoids biochanin A and baicalein in H5N1 influenza A virus-infected cells. Antiviral Res 2013; 97(1): 41-8.
[] [PMID: 23098745]
Gao A-M, Ke Z-P, Wang J-N, Yang J-Y, Chen S-Y, Chen H. Apigenin sensitizes doxorubicin-resistant hepatocellular carcinoma BEL-7402/ADM cells to doxorubicin via inhibiting PI3K/Akt/Nrf2 pathway. Carcinogenesis 2013; 34(8): 1806-14.
[] [PMID: 23563091]
Cheung KL, Kong A-N. Molecular targets of dietary phenethyl isothiocyanate and sulforaphane for cancer chemoprevention. AAPS J 2010; 12(1): 87-97.
[] [PMID: 20013083]
Shapiro TA, Fahey JW, Wade KL, Stephenson KK, Talalay P. Human metabolism and excretion of cancer chemoprotective glucosinolates and isothiocyanates of cruciferous vegetables. Cancer Epidemiol Biomarkers Prev 1998; 7(12): 1091-100.
[PMID: 9865427]
Fahey JW, Wehage SL, Holtzclaw WD, et al. Protection of humans by plant glucosinolates: Efficiency of conversion of glucosinolates to isothiocyanates by the gastrointestinal microflora. Cancer Prev Res (Phila) 2012; 5(4): 603-11.
[] [PMID: 22318753]
Dinkova-Kostova AT, Wang XJ. Induction of the Keap1/Nrf2/ARE pathway by oxidizable diphenols. Chem Biol Interact 2011; 192(1-2): 101-6.
[] [PMID: 20846517]
Jeong W-S, Keum Y-S, Chen C, et al. Differential expression and stability of endogenous nuclear factor E2-related factor 2 (Nrf2) by natural chemopreventive compounds in HepG2 human hepatoma cells. J Biochem Mol Biol 2005; 38(2): 167-76.
[PMID: 15826493]
Keum YS, Owuor ED, Kim BR, Hu R, Kong ANT. Involvement of Nrf2 and JNK1 in the activation of antioxidant responsive element (ARE) by chemopreventive agent phenethyl isothiocyanate (PEITC). Pharm Res 2003; 20(9): 1351-6.
[] [PMID: 14567627]
Korenori Y, Tanigawa S, Kumamoto T, et al. Modulation of Nrf2/Keap1 system by Wasabi 6-methylthiohexyl isothiocyanate in ARE-mediated NQO1 expression. Mol Nutr Food Res 2013; 57(5): 854-64.
[] [PMID: 23390006]
Langer P, Greer MA. Antithyroid activity of some naturally occurring isothiocyanates in vitro. Metabolism 1968; 17(7): 596-605.
[] [PMID: 5656976]
Okulicz M, Hertig I. Benzyl isothiocyanate disturbs lipid metabolism in rats in a way independent of its thyroid impact following in vivo long-term treatment and in vitro adipocytes studies. J Physiol Biochem 2013; 69(1): 75-84.
[] [PMID: 22798227]
Chen C, Pung D, Leong V, et al. Induction of detoxifying enzymes by garlic organosulfur compounds through transcription factor Nrf2: Effect of chemical structure and stress signals. Free Radic Biol Med 2004; 37(10): 1578-90.
[] [PMID: 15477009]
Gong P, Hu B, Cederbaum AI. Diallyl sulfide induces heme oxygenase-1 through MAPK pathway. Arch Biochem Biophys 2004; 432(2): 252-60.
[] [PMID: 15542064]
Shin HA, Cha YY, Park MS, Kim JM, Lim YC. Diallyl sulfide induces growth inhibition and apoptosis of anaplastic thyroid cancer cells by mitochondrial signaling pathway. Oral Oncol 2010; 46(4): E15-8.
[] [PMID: 20219414]
Kalayarasan S, Sriram N, Sureshkumar A, Sudhandiran G. Chromium (VI)-induced oxidative stress and apoptosis is reduced by garlic and its derivative S-allylcysteine through the activation of Nrf2 in the hepatocytes of Wistar rats. J Appl Toxicol 2008; 28(7): 908-19.
[] [PMID: 18548744]
Saravanan G, Ponmurugan P. Antidiabetic effect of S-allylcysteine: Effect on thyroid hormone and circulatory antioxidant system in experimental diabetic rats. J Diabetes Complications 2012; 26(4): 280-5.
[] [PMID: 22541895]
Ping Z, Liu W, Kang Z, et al. Sulforaphane protects brains against hypoxic-ischemic injury through induction of Nrf2-dependent phase 2 enzyme. Brain Res 2010; 1343: 178-85.
[] [PMID: 20417626]
Lin W, Wu RT, Wu T, Khor T-O, Wang H, Kong A-N. Sulforaphane suppressed LPS-induced inflammation in mouse peritoneal macrophages through Nrf2 dependent pathway. Biochem Pharmacol 2008; 76(8): 967-73.
[] [PMID: 18755157]
Bai Y, Cui W, Xin Y, et al. Prevention by sulforaphane of diabetic cardiomyopathy is associated with up-regulation of Nrf2 expression and transcription activation. J Mol Cell Cardiol 2013; 57: 82-95.
[] [PMID: 23353773]
Yoon H-Y, Kang N-I, Lee H-K, Jang KY, Park J-W, Park B-H. Sulforaphane protects kidneys against ischemia-reperfusion injury through induction of the Nrf2-dependent phase 2 enzyme. Biochem Pharmacol 2008; 75(11): 2214-23.
[] [PMID: 18407246]
Wang L, Tian Z, Yang Q, et al. Sulforaphane inhibits thyroid cancer cell growth and invasiveness through the reactive oxygen species-dependent pathway. Oncotarget 2015; 6(28): 25917-31.
[] [PMID: 26312762]
Singh SV, Pan SS, Srivastava SK, et al. Differential induction of NAD(P)H:quinone oxidoreductase by anti-carcinogenic organosulfides from garlic. Biochem Biophys Res Commun 1998; 244(3): 917-20.
[] [PMID: 9535768]
Thomas M, Zhang P, Noordine M-L, Vaugelade P, Chaumontet C, Duée P-H. Diallyl disulfide increases rat h-ferritin, L-ferritin and transferrin receptor genes in vitro in hepatic cells and in vivo in liver. J Nutr 2002; 132(12): 3638-41.
[] [PMID: 12468600]
Wu CC, Sheen LY, Chen HW, Tsai SJ, Lii CK. Effects of organosulfur compounds from garlic oil on the antioxidation system in rat liver and red blood cells. Food Chem Toxicol 2001; 39(6): 563-9.
[] [PMID: 11346486]
Langer P. Antithyroid action in rats of small doses of some naturally occurring compounds. Endocrinology 1966; 79(6): 1117-22.
[] [PMID: 4162816]
Chartoumpekis DV, Ziros PG, Chen JG, Groopman JD, Kensler TW, Sykiotis GP. Broccoli sprout beverage is safe for thyroid hormonal and autoimmune status: Results of a 12-week randomized trial. Food Chem Toxicol 2019; 126: 1-6.
[] [PMID: 30735751]
Cao X, Xiao H, Zhang Y, Zou L, Chu Y, Chu X. 1, 5-Dicaffeoylquinic acid-mediated glutathione synthesis through activation of Nrf2 protects against OGD/reperfusion-induced oxidative stress in astrocytes. Brain Res 2010; 1347: 142-8.
[] [PMID: 20513363]
Kapeta S, Chondrogianni N, Gonos ES. Nuclear erythroid factor 2-mediated proteasome activation delays senescence in human fibroblasts. J Biol Chem 2010; 285(11): 8171-84.
[] [PMID: 20068043]
Papaevgeniou N, Sakellari M, Jha S, et al. 18α-Glycyrrhetinic Acid Proteasome Activator Decelerates Aging and Alzheimer’s Disease Progression in Caenorhabditis elegans and Neuronal Cultures. Antioxid Redox Signal 2016; 25(16): 855-69.
[] [PMID: 26886723]
Hwang YP, Yun HJ, Chun HK, et al. Protective mechanisms of 3-caffeoyl, 4-dihydrocaffeoyl quinic acid from Salicornia herbacea against tert-butyl hydroperoxide-induced oxidative damage. Chem Biol Interact 2009; 181(3): 366-76.
[] [PMID: 19647727]
González-Burgos E, Carretero ME, Gómez-Serranillos MP. Nrf2-dependent neuroprotective activity of diterpenoids isolated from Sideritis spp. J Ethnopharmacol 2013; 147(3): 645-52.
[] [PMID: 23548583]
Yang SM, Ka SM, Hua KF, et al. Antroquinonol mitigates an accelerated and progressive IgA nephropathy model in mice by activating the Nrf2 pathway and inhibiting T cells and NLRP3 inflammasome. Free Radic Biol Med 2013; 61: 285-97.
[] [PMID: 23567192]
Satoh T, Kosaka K, Itoh K, et al. Carnosic acid, a catechol-type electrophilic compound, protects neurons both in vitro and in vivo through activation of the Keap1/Nrf2 pathway via S-alkylation of targeted cysteines on Keap1. J Neurochem 2008; 104(4): 1116-31.
[] [PMID: 17995931]
Martin D, Rojo AI, Salinas M, et al. Regulation of heme oxygenase-1 expression through the phosphatidylinositol 3-kinase/Akt pathway and the Nrf2 transcription factor in response to the antioxidant phytochemical carnosol. J Biol Chem 2004; 279(10): 8919-29.
[] [PMID: 14688281]
Seo WY, Goh AR, Ju SM, et al. Celastrol induces expression of heme oxygenase-1 through ROS/Nrf2/ARE signaling in the HaCaT cells. Biochem Biophys Res Commun 2011; 407(3): 535-40.
[] [PMID: 21414301]
Kim SH, Kang JG, Kim CS, et al. Cytotoxic effect of celastrol alone or in combination with paclitaxel on anaplastic thyroid carcinoma cells. Tumour Biol 2017; 39(5)1010428317698369
[] [PMID: 28459364]
Park SY, Jin ML, Ko MJ, Park G, Choi YW. Anti-neuroinflammatory Effect of Emodin in LPS-Stimulated Microglia: Involvement of AMPK/Nrf2 Activation. Neurochem Res 2016; 41(11): 2981-92.
[] [PMID: 27538959]
Jing N, Jing Z. ZhanSheng Z, Hui G, Qing W. Pro-apoptic effect of Aloe emodin on human thyroid cancer cell K1. Xiandai Shengwu Yixue Jinzhan 2010; 10: 3225-7.
Lyu JH, Lee GS, Kim KH, et al. ent-kaur-16-en-19-oic Acid, isolated from the roots of Aralia continentalis, induces activation of Nrf2. J Ethnopharmacol 2011; 137(3): 1442-9.
[] [PMID: 21884778]
González-Burgos E, Carretero ME, Gómez-Serranillos MP. Kaurane diterpenes from Sideritis spp. exert a cytoprotective effect against oxidative injury that is associated with modulation of the Nrf2 system. Phytochemistry 2013; 93: 116-23.
[] [PMID: 23642391]
Yap WH, Khoo KS, Ho ASH, Lim YM. Maslinic acid induces HO-1 and NOQ1 expression via activation of Nrf2 transcription factor. Biomed Prevent Nutr 2012; 2: 51-8.
Lee Y-M, Auh QS, Lee D-W, et al. Involvement of Nrf2-mediated upregulation of heme oxygenase-1 in mollugin-induced growth inhibition and apoptosis in human oral cancer cells. BioMed Res Int 2013; 2013210604
[] [PMID: 23738323]
Du Y, Villeneuve NF, Wang XJ, et al. Oridonin confers protection against arsenic-induced toxicity through activation of the Nrf2-mediated defensive response. Environ Health Perspect 2008; 116(9): 1154-61.
[] [PMID: 18795156]
Son TG, Camandola S, Arumugam TV, et al. Plumbagin, a novel Nrf2/ARE activator, protects against cerebral ischemia. J Neurochem 2010; 112(5): 1316-26.
[] [PMID: 20028456]
Yu J, Ren P, Zhong T, et al. Pseudolaric acid B inhibits proliferation in SW579 human thyroid squamous cell carcinoma. Mol Med Rep 2015; 12(5): 7195-202.
[] [PMID: 26460192]
Lee D-S, Choi H-G, Wan Woo K, et al. Pulchellamin G, an amino acid-sesquiterpene lactone, from Saussurea pulchella suppresses lipopolysaccharide-induced inflammatory responses via heme oxygenase-1 expression in murine peritoneal macrophages. Eur J Pharmacol 2013; 715(1-3): 123-32.
[] [PMID: 23742862]
Tao S, Zheng Y, Lau A, et al. Tanshinone I activates the Nrf2-dependent antioxidant response and protects against As(III)-induced lung inflammation in vitro and in vivo. Antioxid Redox Signal 2013; 19(14): 1647-61.
[] [PMID: 23394605]
Zhang H-S, Wang S-Q. Nrf2 is involved in the effect of tanshinone IIA on intracellular redox status in human aortic smooth muscle cells. Biochem Pharmacol 2007; 73(9): 1358-66.
[] [PMID: 17303087]
Chen F, Liu Y, Wang S, et al. Triptolide, a Chinese herbal extract, enhances drug sensitivity of resistant myeloid leukemia cell lines through downregulation of HIF-1α and Nrf2. Pharmacogenomics 2013; 14(11): 1305-17.
[] [PMID: 23930677]
Yu H, Shi L, Zhao S, et al. Triptolide attenuates myocardial ischemia/reperfusion injuries in rats by inducing the activation of Nrf2/HO-1 defense pathway. Cardiovasc Toxicol 2016; 16(4): 325-35.
[] [PMID: 26391895]
Zhu W, Hu H, Qiu P, Yan G. Triptolide induces apoptosis in human anaplastic thyroid carcinoma cells by a p53-independent but NF-kappaB-related mechanism. Oncol Rep 2009; 22(6): 1397-401.
[PMID: 19885592]
Nakamura Y, Yoshida C, Murakami A, Ohigashi H, Osawa T, Uchida K. Zerumbone, a tropical ginger sesquiterpene, activates phase II drug metabolizing enzymes. FEBS Lett 2004; 572(1-3): 245-50.
[] [PMID: 15304356]
Park SY, Park DJ, Kim YH, Kim Y, Choi Y-W, Lee S-J. Schisandra chinensis α-iso-cubebenol induces heme oxygenase-1 expression through PI3K/Akt and Nrf2 signaling and has anti-inflammatory activity in Porphyromonas gingivalis lipopolysaccharide-stimulated macrophages. Int Immunopharmacol 2011; 11(11): 1907-15.
[] [PMID: 21840424]
Palliyaguru DL, Chartoumpekis DV, Wakabayashi N, et al. Withaferin A induces Nrf2-dependent protection against liver injury: Role of Keap1-independent mechanisms. Free Radic Biol Med 2016; 101: 116-28.
[] [PMID: 27717869]
Yarnell E, Abascal K. Botanical medicine for thyroid regulation. Altern Complement Ther 2006; 12: 107-12.
Chandra AK, Mukhopadhyay S, Lahari D, Tripathy S. Goitrogenic content of Indian cyanogenic plant foods & their in vitro anti-thyroidal activity. Indian J Med Res 2004; 119(5): 180-5.
[PMID: 15218979]
Ferreira ACF, Rosenthal D, Carvalho DP. Thyroid peroxidase inhibition by Kalanchoe brasiliensis aqueous extract. Food Chem Toxicol 2000; 38(5): 417-21.
[] [PMID: 10762727]
Kar A, Panda S, Bharti S. Relative efficacy of three medicinal plant extracts in the alteration of thyroid hormone concentrations in male mice. J Ethnopharmacol 2002; 81(2): 281-5.
[] [PMID: 12065164]
Chandra AK, De N. Goitrogenic/antithyroidal potential of green tea extract in relation to catechin in rats. Food Chem Toxicol 2010; 48(8-9): 2304-11.
[] [PMID: 20561943]
Rinner B, Siegl V, Pürstner P, et al. Activity of novel plant extracts against medullary thyroid carcinoma cells. Anticancer Res 2004; 24(2A): 495-500.
[PMID: 15152949]
Gerhäuser C, Klimo K, Hümmer W, et al. Identification of 3-hydroxy-β-damascone and related carotenoid-derived aroma compounds as novel potent inducers of Nrf2-mediated phase 2 response with concomitant anti-inflammatory activity. Mol Nutr Food Res 2009; 53(10): 1237-44.
[] [PMID: 19753606]
Chen H-H, Chen Y-T, Huang Y-W, Tsai H-J, Kuo C-C. 4-Ketopinoresinol, a novel naturally occurring ARE activator, induces the Nrf2/HO-1 axis and protects against oxidative stress-induced cell injury via activation of PI3K/AKT signaling. Free Radic Biol Med 2012; 52(6): 1054-66.
[] [PMID: 22245092]
Lee B-H, Hsu W-H, Chang Y-Y, Kuo H-F, Hsu Y-W, Pan T-M. Ankaflavin: A natural novel PPARγ agonist upregulates Nrf2 to attenuate methylglyoxal-induced diabetes in vivo. Free Radic Biol Med 2012; 53(11): 2008-16.
[] [PMID: 23022408]
Kim KC, Kang KA, Zhang R, et al. Up-regulation of Nrf2-mediated heme oxygenase-1 expression by eckol, a phlorotannin compound, through activation of Erk and PI3K/Akt. Int J Biochem Cell Biol 2010; 42(2): 297-305.
[] [PMID: 19931411]
Ohnuma T, Komatsu T, Nakayama S, Nishiyama T, Ogura K, Hiratsuka A. Induction of antioxidant and phase 2 drug-metabolizing enzymes by falcarindiol isolated from Notopterygium incisum extract, which activates the Nrf2/ARE pathway, leads to cytoprotection against oxidative and electrophilic stress. Arch Biochem Biophys 2009; 488(1): 34-41.
[] [PMID: 19527678]
Wang Y, Zhao H, Lin C, et al. Exhibits Anti-inflammatory Effects in LPS-Stimulated BV2 Microglia Cells Through Activation of Nrf2/HO-1 Signaling Pathway. Neurochem Res 2016; 41(4): 659-65.
[] [PMID: 26498935]
Liu C-L, Chiu Y-T, Hu M-L. Fucoxanthin enhances HO-1 and NQO1 expression in murine hepatic BNL CL.2 cells through activation of the Nrf2/ARE system partially by its pro-oxidant activity. J Agric Food Chem 2011; 59(20): 11344-51.
[] [PMID: 21919437]
Lee K-M, Kang K, Lee SB, Nho CW. Nuclear factor-E2 (Nrf2) is regulated through the differential activation of ERK1/2 and PKC α/βII by Gymnasterkoreayne B. Cancer Lett 2013; 330(2): 225-32.
[] [PMID: 23219897]
Boesch-Saadatmandi C, Wagner AE, Graeser AC, Hundhausen C, Wolffram S, Rimbach G. Ochratoxin A impairs Nrf2-dependent gene expression in porcine kidney tubulus cells. J Anim Physiol Anim Nutr (Berl) 2009; 93(5): 547-54.
[] [PMID: 18547363]
Kay HY, Kim YW, Ryu DH, Sung SH, Hwang SJ, Kim SG. Nrf2-mediated liver protection by sauchinone, an antioxidant lignan, from acetaminophen toxicity through the PKCδ-GSK3β pathway. Br J Pharmacol 2011; 163(8): 1653-65.
[] [PMID: 21039417]
Chiu PY, Chen N, Leong PK, Leung HY, Ko KM. Schisandrin B elicits a glutathione antioxidant response and protects against apoptosis via the redox-sensitive ERK/Nrf2 pathway in H9c2 cells. Mol Cell Biochem 2011; 350(1-2): 237-50.
[] [PMID: 21193948]
Kang KA, Lee KH, Park JW, et al. Triphlorethol-A induces heme oxygenase-1 via activation of ERK and NF-E2 related factor 2 transcription factor. FEBS Lett 2007; 581(10): 2000-8.
[] [PMID: 17467702]
Egner PA, Chen JG, Zarth AT, et al. Rapid and sustainable detoxication of airborne pollutants by broccoli sprout beverage: Results of a randomized clinical trial in China. Cancer Prev Res (Phila) 2014; 7(8): 813-23.
[] [PMID: 24913818]

© 2022 Bentham Science Publishers | Privacy Policy