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The Cytoprotective Activity of Nrf2 Is Regulated by Phytochemicals (Sulforaphane, Curcumin, and Silymarin)

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Plant Antioxidants and Health

Part of the book series: Reference Series in Phytochemistry ((RSP))

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Abstract

The evolution of species has encouraged organisms to adapt to their environment; in this process, an aerobic metabolism was the product of exposure to certain atmospheric conditions. Oxygen consumption in most cellular systems results in the production of reactive oxygen species (ROS) that may be capable of causing cellular damage at a certain level; however, these molecules are crucial to trigger cell signaling pathways for the maintenance of homeostasis. The high production of ROS increases oxidative stress (OS) which may affect some cellular structures. Thus, cells have to develop effective cytoprotective systems to defend themselves against damage. Nuclear factor erythroid 2-related factor 2 (Nrf2) is the master regulator of protection; its activation induces the Nrf2/Keap1/ARE pathway for the expression of a wide range of genes involved in detoxification and the antioxidant response. Researchers have paid special attention to the mechanism that favors this pathway and have found that some phytochemicals are potent Nrf2 activators. Therefore, in this work, we provide an overview of three of the most efficient bioactivators and the evidence supporting them as potential therapeutic elements under different medical conditions.

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Abbreviations

6-OHDA :

6-Hydroxydopamine

ABP:

Aminobiphenyl

AD:

Alzheimer’s Disease

ADN:

Deoxyribonucleic Acid

ALDH:

Aldehyde Dehydrogenase

ARE:

Antioxidant Response Element

Aβ:

Amyloid-β

B[a]P:

Benzo[a]pyrene

Bcl-2:

B-cell Lymphoma 2

BPDE:

[a]P-7,8-Dihydrodiol-9,10-Epoxide

Cas:

Caspase

CAT:

Catalase

CCl4:

Carbon Tetrachloride

CDDP:

Cisplatin

CIN :

Contrast-Induced Nephropathy

Cmax:

Maximal Serum Concentration

COX2:

Cyclooxygenase 2

CS:

Cigarette Smoke

CURS:

Curcumin Synthase

Cys:

Cysteine

DCS:

Diketone-CoA Synthase

DMSO:

Dimethyl Sulfoxide

DYRK2:

Dual Specificity-Tyrosine-Regulated Kinase 2

ERK:

Extracellular-Signal Regulated Kinases

EVVE:

Ethanolic Vitis vinifera Extract

FR:

Free Radicals

GCL:

Glutamate Cysteine Ligase

GCLC:

Glutamate Cysteine Ligase Catalytic

GCLM:

Glutamate Cysteine Ligase Modifier

GCS:

Glutamyl Cysteine Synthetase

GO:

Glucose Oxidase

GPx:

Glutathione Peroxidase

GR:

Glutathione Reductase

GSH:

Glutathione

GSL:

Glucosinolates

GST:

Glutathione S-Transferase

H2O2:

Hydrogen Peroxide

HCl:

Hydrochloric Acid

hepg2:

Hepatoma Cells

HO-1:

Heme-Oxygenase 1

IL-6:

Interleukin-6

iNos:

Nitric Oxide Synthase

JNK:

c-Jun N-Terminal Kinases

Keap1:

Kelch-Like ECH-Associated Protein 1

MAPK:

Mitogen-Activated Protein Kinases

MDA:

Malondialdehyde

Mkp-1:

Protein Kinase Phosphatase 1

mRNA:

Messenger Ribonucleic Acid

NADPH :

Nicotinamide Adenine Dinucleotide Phosphate, Reduced

NASH:

Non-alcoholic Steatohepatitis

Neh:

Homology Regions and Domains

NF-κβ:

Nuclear Factor κβ

NQO1:

Quinone Oxidoreductase 1

Nrf2:

Nuclear Factor Erythroid 2-Related Factor 2

O2:

Oxygen

O2−:

Superoxide Anion Radical

OH−:

Hydroxyl Radical

OS:

Oxidative Stress

PD:

Parkinson’s Disease

Pi3k:

Phosphatidylinositol 3-Kinase

PKB:

Protein Kinase B

PXR:

Pregnane X Receptor

QSAR:

Quantitative Structure–Activity Relationship

RNS:

Reactive Nitrogen Species

ROS:

Reactive Oxygen Species

RPE:

Retinal Pigment Epithelial Cells

RSV:

Respiratory Syncytial Virus

SCD:

Sickle Cell Disease

SCI:

Spinal Cord Injury

SFN:

Sulforaphane

Sm:

Silymarin

SOD:

Superoxide Dismutase

TGF-β:

Transforming Growth Factor Beta

TNF-α:

Tumor Necrosis Factor-Alpha

UGT:

UDP-Glucuronosyltransferase

UV:

Ultraviolet

References

  1. Halliwell B (2007) Biochemistry of oxidative stress. Biochem Soc Trans 35:1147–1150. https://doi.org/10.1042/BST0351147

    Article  CAS  PubMed  Google Scholar 

  2. Handy DE, Loscalzo J (2012) Redox regulation of mitochondrial function. Antioxid Redox Signal 16:1323–1367. https://doi.org/10.1089/ars.2011.4123

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Murphy MP (2009) How mitochondria produce reactive oxygen species. Biochem J 417:1–13. https://doi.org/10.1042/BJ20081386

    Article  CAS  PubMed  Google Scholar 

  4. Schieber M, Chandel NS (2014) ROS function in redox signaling and oxidative stress. Curr Biol 24:R453–R462. https://doi.org/10.1016/j.cub.2014.03.034

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Thannickal VJ, Fanburg BL (2000) Reactive oxygen species in cell signaling. Am J Physiol Lung Cell Mol Physiol 279:L1005–L1028. https://doi.org/10.1152/ajplung.2000.279.6.L1005

    Article  CAS  PubMed  Google Scholar 

  6. Calabrese EJ, Iavicoli I, Calabrese V (2013) Hormesis: its impact on medicine and health. Hum Exp Toxicol 32:120–152. https://doi.org/10.1177/0960327112455069

    Article  CAS  PubMed  Google Scholar 

  7. Bryan HK, Olayanju A, Goldring CE, Park BK (2013) The Nrf2 cell defence pathway: Keap1-dependent and -independent mechanisms of regulation. Biochem Pharmacol 85:705–717. https://doi.org/10.1016/j.bcp.2012.11.016

    Article  CAS  PubMed  Google Scholar 

  8. Tebay LE, Robertson H, Durant ST, Vitale SR, Penning TM, Dinkova-Kostova AT, Hayes JD (2015) Mechanisms of activation of the transcription factor Nrf2 by redox stressors, nutrient cues, and energy status and the pathways through which it attenuates degenerative disease. Free Radic Biol Med 88:108–146. https://doi.org/10.1016/j.freeradbiomed.2015.06.021

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Vargas-Mendoza N, Morales-Gonzalez A, Madrigal-Santillan EO, Madrigal-Bujaidar E, Alvarez-Gonzalez I, Garcia-Melo LF, Anguiano-Robledo L, Fregoso-Aguilar T, Morales-Gonzalez JA (2019) Antioxidant and adaptative response mediated by Nrf2 during physical exercise. Antioxidants (Basel):8. https://doi.org/10.3390/antiox8060196

  10. Kwak MK, Wakabayashi N, Itoh K, Motohashi H, Yamamoto M, Kensler TW (2003) Modulation of gene expression by cancer chemopreventive dithiolethiones through the Keap1-Nrf2 pathway. Identification of novel gene clusters for cell survival. J Biol Chem 278:8135–8145. https://doi.org/10.1074/jbc.M211898200

    Article  CAS  PubMed  Google Scholar 

  11. Jiang T, Huang Z, Lin Y, Zhang Z, Fang D, Zhang DD (2010) The protective role of Nrf2 in streptozotocin-induced diabetic nephropathy. Diabetes 59:850–860. https://doi.org/10.2337/db09-1342

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Tu W, Wang H, Li S, Liu Q, Sha H (2019) The anti-inflammatory and anti-oxidant mechanisms of the Keap1/Nrf2/ARE signaling pathway in chronic diseases. Aging Dis 10:637–651. https://doi.org/10.14336/ad.2018.0513

    Article  PubMed  PubMed Central  Google Scholar 

  13. Moi P, Chan K, Asunis I, Cao A, Kan YW (1994) Isolation of NF-E2-related factor 2 (Nrf2), a NF-E2-like basic leucine zipper transcriptional activator that binds to the tandem NF-E2/AP1 repeat of the beta-globin locus control region. Proc Natl Acad Sci U S A 91:9926–9930. https://doi.org/10.1073/pnas.91.21.9926

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Hayes JD, Dinkova-Kostova AT (2014) The Nrf2 regulatory network provides an interface between redox and intermediary metabolism. Trends Biochem Sci 39:199–218. https://doi.org/10.1016/j.tibs.2014.02.002

    Article  CAS  PubMed  Google Scholar 

  15. Itoh K, Wakabayashi N, Katoh Y, Ishii T, Igarashi K, Engel JD, Yamamoto M (1999) Keap1 represses nuclear activation of antioxidant responsive elements by Nrf2 through binding to the amino-terminal Neh2 domain. Genes Dev 13:76–86. https://doi.org/10.1101/gad.13.1.76

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Itoh K, Igarashi K, Hayashi N, Nishizawa M, Yamamoto M (1995) Cloning and characterization of a novel erythroid cell-derived CNC family transcription factor heterodimerizing with the small Maf family proteins. Mol Cell Biol 15:4184–4193. https://doi.org/10.1128/mcb.15.8.4184

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Namani A, Li Y, Wang XJ, Tang X (2014) Modulation of NRF2 signaling pathway by nuclear receptors: implications for cancer. Biochim Biophys Acta 1843:1875–1885. https://doi.org/10.1016/j.bbamcr.2014.05.003

    Article  CAS  PubMed  Google Scholar 

  18. Eggler AL, Small E, Hannink M, Mesecar AD (2009) Cul3-mediated Nrf2 ubiquitination and antioxidant response element (ARE) activation are dependent on the partial molar volume at position 151 of Keap1. Biochem J 422:171–180. https://doi.org/10.1042/BJ20090471

    Article  CAS  PubMed  Google Scholar 

  19. Tong KI, Padmanabhan B, Kobayashi A, Shang C, Hirotsu Y, Yokoyama S, Yamamoto M (2007) Different electrostatic potentials define ETGE and DLG motifs as hinge and latch in oxidative stress response. Mol Cell Biol 27:7511–7521. https://doi.org/10.1128/MCB.00753-07

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Raghunath A, Sundarraj K, Nagarajan R, Arfuso F, Bian J, Kumar AP, Sethi G, Perumal E (2018) Antioxidant response elements: discovery, classes, regulation and potential applications. Redox Biol 17:297–314. https://doi.org/10.1016/j.redox.2018.05.002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Jain A, Lamark T, Sjottem E, Larsen KB, Awuh JA, Overvatn A, McMahon M, Hayes JD, Johansen T (2010) p62/SQSTM1 is a target gene for transcription factor NRF2 and creates a positive feedback loop by inducing antioxidant response element-driven gene transcription. J Biol Chem 285:22576–22591. https://doi.org/10.1074/jbc.M110.118976

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Lau A, Wang XJ, Zhao F, Villeneuve NF, Wu T, Jiang T, Sun Z, White E, Zhang DD (2010) A noncanonical mechanism of Nrf2 activation by autophagy deficiency: direct interaction between Keap1 and p62. Mol Cell Biol 30:3275–3285. https://doi.org/10.1128/MCB.00248-10

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Komatsu M, Kurokawa H, Waguri S, Taguchi K, Kobayashi A, Ichimura Y, Sou YS, Ueno I, Sakamoto A, Tong KI, Kim M, Nishito Y, Iemura S, Natsume T, Ueno T, Kominami E, Motohashi H, Tanaka K, Yamamoto M (2010) The selective autophagy substrate p62 activates the stress responsive transcription factor Nrf2 through inactivation of Keap1. Nat Cell Biol 12:213–223. https://doi.org/10.1038/ncb2021

    Article  CAS  PubMed  Google Scholar 

  24. Chen W, Sun Z, Wang XJ, Jiang T, Huang Z, Fang D, Zhang DD (2009) Direct interaction between Nrf2 and p21(Cip1/WAF1) upregulates the Nrf2-mediated antioxidant response. Mol Cell 34:663–673. https://doi.org/10.1016/j.molcel.2009.04.029

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Gorrini C, Baniasadi PS, Harris IS, Silvester J, Inoue S, Snow B, Joshi PA, Wakeham A, Molyneux SD, Martin B, Bouwman P, Cescon DW, Elia AJ, Winterton-Perks Z, Cruickshank J, Brenner D, Tseng A, Musgrave M, Berman HK, Khokha R, Jonkers J, Mak TW, Gauthier ML (2013) BRCA1 interacts with Nrf2 to regulate antioxidant signaling and cell survival. J Exp Med 210:1529–1544. https://doi.org/10.1084/jem.20121337

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Mendoza N, E-SE (2018) Introduction to phytochemicals: secondary metabolites from plants with active principles for pharmacological importance. In: Toshiki A (ed) Phytochemicals. Source of antioxidants and role in disease prevention. InTech, pp 25–47

    Google Scholar 

  27. Koche D, Shirsat R, Kawale M (2018, 2016) An overerview of major classes of phytochemicals: their types and role in disease prevention. Hislopia J 9

    Google Scholar 

  28. Lopez-Romero D, Izquierdo-Vega JA, Morales-Gonzalez JA, Madrigal-Bujaidar E, Chamorro-Cevallos G, Sanchez-Gutierrez M, Betanzos-Cabrera G, Alvarez-Gonzalez I, Morales-Gonzalez A, Madrigal-Santillan E (2018) Evidence of some natural products with antigenotoxic effects. Part 2: plants, vegetables, and natural resin. Nutrients 10. https://doi.org/10.3390/nu10121954

  29. Liu RH (2004) Potential synergy of phytochemicals in cancer prevention: mechanism of action. J Nutr 134:3479S–3485S. https://doi.org/10.1093/jn/134.12.3479S

    Article  CAS  PubMed  Google Scholar 

  30. Robledinos-Anton N, Fernandez-Gines R, Manda G, Cuadrado A (2019) Activators and inhibitors of NRF2: a review of their potential for clinical development. Oxidative Med Cell Longev 2019:9372182. https://doi.org/10.1155/2019/9372182

    Article  CAS  Google Scholar 

  31. Saito R, Suzuki T, Hiramoto K, Asami S, Naganuma E, Suda H, Iso T, Yamamoto H, Morita M, Baird L, Furusawa Y, Negishi T, Ichinose M, Yamamoto M (2016) Characterizations of three major cysteine sensors of Keap1 in stress response. Mol Cell Biol 36:271–284. https://doi.org/10.1128/MCB.00868-15

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Yamamoto T, Suzuki T, Kobayashi A, Wakabayashi J, Maher J, Motohashi H, Yamamoto M (2008) Physiological significance of reactive cysteine residues of Keap1 in determining Nrf2 activity. Mol Cell Biol 28:2758–2770. https://doi.org/10.1128/MCB.01704-07

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Yang L, Palliyaguru DL, Kensler TW (2016) Frugal chemoprevention: targeting Nrf2 with foods rich in sulforaphane. Semin Oncol 43:146–153. https://doi.org/10.1053/j.seminoncol.2015.09.013

    Article  CAS  PubMed  Google Scholar 

  34. Houghton CA, Fassett RG, Coombes JS (2013) Sulforaphane: translational research from laboratory bench to clinic. Nutr Rev 71:709–726. https://doi.org/10.1111/nure.12060

    Article  PubMed  Google Scholar 

  35. Houghton CA, Fassett RG, Coombes JS (2016) Sulforaphane and other nutrigenomic Nrf2 activators: can the clinician’s expectation be matched by the reality? Oxidative Med Cell Longev 2016:7857186. https://doi.org/10.1155/2016/7857186

    Article  CAS  Google Scholar 

  36. Latté KP, Appel KE, Lampen A (2011) Health benefits and possible risks of broccoli – an overview. Food Chem Toxicol 49:3287–3309. https://doi.org/10.1016/j.fct.2011.08.019

    Article  CAS  PubMed  Google Scholar 

  37. USDA Food composition databases

    Google Scholar 

  38. Slavin JL, Lloyd B (2012) Health benefits of fruits and vegetables. Adv Nutr 3:506–516. https://doi.org/10.3945/an.112.002154

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Kapusta-Duch J, Kopeć A, Piatkowska E, Borczak B, Leszczyńska T (2012) The beneficial effects of Brassica vegetables on human health. Rocz Panstw Zakl Hig 63:389–395

    CAS  PubMed  Google Scholar 

  40. Pancholi S (2018) Antibacterial potential of ethanolic extract of broccoli (Brassica oleracea var. italica) against human pathogenic bacteria. Oxid Med Cell Longev 10

    Google Scholar 

  41. de Figueiredo SM, Filho SA, Nogueira-Machado JA, Caligiorne RB (2013) The anti-oxidant properties of isothiocyanates: a review. Recent Pat Endocr Metab Immune Drug Discov 7:213–225. https://doi.org/10.2174/18722148113079990011

    Article  CAS  PubMed  Google Scholar 

  42. Abellán Á, Domínguez-Perles R, Moreno DA, García-Viguera C (2019) Sorting out the value of cruciferous sprouts as sources of bioactive compounds for nutrition and health. Nutrients 11. https://doi.org/10.3390/nu11020429

  43. de Figueiredo SM, Binda NS, Nogueira-Machado JA, Vieira-Filho SA, Caligiorne RB (2015) The antioxidant properties of organosulfur compounds (sulforaphane). Recent Pat Endocr Metab Immune Drug Discov 9:24–39. https://doi.org/10.2174/1872214809666150505164138

    Article  CAS  PubMed  Google Scholar 

  44. Kamal MM, Akter S, Lin CN, Nazzal S (2020) Sulforaphane as an anticancer molecule: mechanisms of action, synergistic effects, enhancement of drug safety, and delivery systems. Arch Pharm Res 43:371–384. https://doi.org/10.1007/s12272-020-01225-2

    Article  CAS  PubMed  Google Scholar 

  45. Nakagawa K, Umeda T, Higuchi O, Tsuzuki T, Suzuki T, Miyazawa T (2006) Evaporative light-scattering analysis of sulforaphane in broccoli samples: quality of broccoli products regarding sulforaphane contents. J Agric Food Chem 54:2479–2483. https://doi.org/10.1021/jf051823g

    Article  CAS  PubMed  Google Scholar 

  46. Xu TRD, Sun X, Yang G (2012) Dual roles of sulforaphane in cancer treatment. Anti-Cancer Agents Med Chem 12:1132–1142

    Article  CAS  Google Scholar 

  47. Ho E, Clarke JD, Dashwood RH (2009) Dietary sulforaphane, a histone deacetylase inhibitor for cancer prevention. J Nutr 139:2393–2396. https://doi.org/10.3945/jn.109.113332

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Prochaska HJ, Santamaria AB, Talalay P (1992) Rapid detection of inducers of enzymes that protect against carcinogens. Proc Natl Acad Sci U S A 89:2394–2398. https://doi.org/10.1073/pnas.89.6.2394

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Zhang Y, Talalay P, Cho CG, Posner GH (1992) A major inducer of anticarcinogenic protective enzymes from broccoli: isolation and elucidation of structure. Proc Natl Acad Sci U S A 89:2399–2403. https://doi.org/10.1073/pnas.89.6.2399

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Cornblatt BS, Ye L, Dinkova-Kostova AT, Erb M, Fahey JW, Singh NK, Chen MS, Stierer T, Garrett-Mayer E, Argani P, Davidson NE, Talalay P, Kensler TW, Visvanathan K (2007) Preclinical and clinical evaluation of sulforaphane for chemoprevention in the breast. Carcinogenesis 28:1485–1490. https://doi.org/10.1093/carcin/bgm049

    Article  CAS  PubMed  Google Scholar 

  51. Kallifatidis G, Rausch V, Baumann B, Apel A, Beckermann BM, Groth A, Mattern J, Li Z, Kolb A, Moldenhauer G, Altevogt P, Wirth T, Werner J, Schemmer P, Büchler MW, Salnikov AV, Herr I (2009) Sulforaphane targets pancreatic tumour-initiating cells by NF-kappaB-induced antiapoptotic signalling. Gut 58:949–963. https://doi.org/10.1136/gut.2008.149039

    Article  CAS  PubMed  Google Scholar 

  52. Sharma C, Sadrieh L, Priyani A, Ahmed M, Hassan AH, Hussain A (2011) Anti-carcinogenic effects of sulforaphane in association with its apoptosis-inducing and anti-inflammatory properties in human cervical cancer cells. Cancer Epidemiol 35:272–278. https://doi.org/10.1016/j.canep.2010.09.008

    Article  CAS  PubMed  Google Scholar 

  53. Li SH, Fu J, Watkins DN, Srivastava RK, Shankar S (2013) Sulforaphane regulates self-renewal of pancreatic cancer stem cells through the modulation of sonic hedgehog-GLI pathway. Mol Cell Biochem 373:217–227. https://doi.org/10.1007/s11010-012-1493-6

  54. Jo GH, Kim GY, Kim WJ, Park KY, Choi YH (2014) Sulforaphane induces apoptosis in T24 human urinary bladder cancer cells through a reactive oxygen species-mediated mitochondrial pathway: the involvement of endoplasmic reticulum stress and the Nrf2 signaling pathway. Int J Oncol 45:1497–1506. https://doi.org/10.3892/ijo.2014.2536

    Article  CAS  PubMed  Google Scholar 

  55. Atwell LL, Beaver LM, Shannon J, Williams DE, Dashwood RH, Ho E (2015) Epigenetic regulation by sulforaphane: opportunities for breast and prostate cancer chemoprevention. Curr Pharmacol Rep 1:102–111. https://doi.org/10.1007/s40495-014-0002-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Chen CY, Yu ZY, Chuang YS, Huang RM, Wang TC (2015) Sulforaphane attenuates EGFR signaling in NSCLC cells. J Biomed Sci 22:38. https://doi.org/10.1186/s12929-015-0139-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Talalay P (2000) Chemoprotection against cancer by induction of phase 2 enzymes. Biofactors 12:5–11. https://doi.org/10.1002/biof.5520120102

    Article  CAS  PubMed  Google Scholar 

  58. Navarro SL, Li F, Lampe JW (2011) Mechanisms of action of isothiocyanates in cancer chemoprevention: an update. Food Funct 2:579–587. https://doi.org/10.1039/c1fo10114e

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Thimmulappa RK, Mai KH, Srisuma S, Kensler TW, Yamamoto M, Biswal S (2002) Identification of Nrf2-regulated genes induced by the chemopreventive agent sulforaphane by oligonucleotide microarray. Cancer Res 62:5196–5203

    CAS  PubMed  Google Scholar 

  60. McWalter GK, Higgins LG, McLellan LI, Henderson CJ, Song L, Thornalley PJ, Itoh K, Yamamoto M, Hayes JD (2004) Transcription factor Nrf2 is essential for induction of NAD(P)H:quinone oxidoreductase 1, glutathione S-transferases, and glutamate cysteine ligase by broccoli seeds and isothiocyanates. J Nutr 134:3499s–3506s. https://doi.org/10.1093/jn/134.12.3499S

    Article  CAS  PubMed  Google Scholar 

  61. Kraft AD, Johnson DA, Johnson JA (2004) Nuclear factor E2-related factor 2-dependent antioxidant response element activation by tert-butylhydroquinone and sulforaphane occurring preferentially in astrocytes conditions neurons against oxidative insult. J Neurosci 24:1101–1112. https://doi.org/10.1523/jneurosci.3817-03.2004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Gao X, Talalay P (2004) Induction of phase 2 genes by sulforaphane protects retinal pigment epithelial cells against photooxidative damage. Proc Natl Acad Sci U S A 101:10446–10451. https://doi.org/10.1073/pnas.0403886101

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Lo SC, Hannink M (2006) PGAM5, a Bcl-XL-interacting protein, is a novel substrate for the redox-regulated Keap1-dependent ubiquitin ligase complex. J Biol Chem 281:37893–37903. https://doi.org/10.1074/jbc.M606539200

    Article  CAS  PubMed  Google Scholar 

  64. Kwak MK, Cho JM, Huang B, Shin S, Kensler TW (2007) Role of increased expression of the proteasome in the protective effects of sulforaphane against hydrogen peroxide-mediated cytotoxicity in murine neuroblastoma cells. Free Radic Biol Med 43:809–817. https://doi.org/10.1016/j.freeradbiomed.2007.05.029

    Article  CAS  PubMed  Google Scholar 

  65. Cho HY, Imani F, Miller-DeGraff L, Walters D, Melendi GA, Yamamoto M, Polack FP, Kleeberger SR (2009) Antiviral activity of Nrf2 in a murine model of respiratory syncytial virus disease. Am J Respir Crit Care Med 179:138–150. https://doi.org/10.1164/rccm.200804-535OC

    Article  CAS  PubMed  Google Scholar 

  66. Yeh CT, Chiu HF, Yen GC (2009) Protective effect of sulforaphane on indomethacin-induced cytotoxicity via heme oxygenase-1 expression in human intestinal Int 407 cells. Mol Nutr Food Res 53:1166–1176. https://doi.org/10.1002/mnfr.200800558

    Article  CAS  PubMed  Google Scholar 

  67. Park HM, Kim JA, Kwak MK (2009) Protection against amyloid beta cytotoxicity by sulforaphane: role of the proteasome. Arch Pharm Res 32:109–115. https://doi.org/10.1007/s12272-009-1124-2

    Article  CAS  PubMed  Google Scholar 

  68. Dash PK, Zhao J, Orsi SA, Zhang M, Moore AN (2009) Sulforaphane improves cognitive function administered following traumatic brain injury. Neurosci Lett 460:103–107. https://doi.org/10.1016/j.neulet.2009.04.028

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Guerrero-Beltrán CE, Calderón-Oliver M, Tapia E, Medina-Campos ON, Sánchez-González DJ, Martínez-Martínez CM, Ortiz-Vega KM, Franco M, Pedraza-Chaverri J (2010) Sulforaphane protects against cisplatin-induced nephrotoxicity. Toxicol Lett 192:278–285. https://doi.org/10.1016/j.toxlet.2009.11.007

    Article  CAS  PubMed  Google Scholar 

  70. Ping Z, Liu W, Kang Z, Cai J, Wang Q, Cheng N, Wang S, Wang S, Zhang JH, Sun X (2010) Sulforaphane protects brains against hypoxic-ischemic injury through induction of Nrf2-dependent phase 2 enzyme. Brain Res 1343:178–185. https://doi.org/10.1016/j.brainres.2010.04.036

    Article  CAS  PubMed  Google Scholar 

  71. Ding Y, Paonessa JD, Randall KL, Argoti D, Chen L, Vouros P, Zhang Y (2010) Sulforaphane inhibits 4-aminobiphenyl-induced DNA damage in bladder cells and tissues. Carcinogenesis 31:1999–2003. https://doi.org/10.1093/carcin/bgq183

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Suganuma H, Fahey JW, Bryan KE, Healy ZR, Talalay P (2011) Stimulation of phagocytosis by sulforaphane. Biochem Biophys Res Commun 405:146–151. https://doi.org/10.1016/j.bbrc.2011.01.025

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Starrett W, Blake DJ (2011) Sulforaphane inhibits de novo synthesis of IL-8 and MCP-1 in human epithelial cells generated by cigarette smoke extract. J Immunotoxicol 8:150–158. https://doi.org/10.3109/1547691x.2011.558529

    Article  CAS  PubMed  Google Scholar 

  74. Leoncini E, Malaguti M, Angeloni C, Motori E, Fabbri D, Hrelia S (2011) Cruciferous vegetable phytochemical sulforaphane affects phase II enzyme expression and activity in rat cardiomyocytes through modulation of Akt signaling pathway. J Food Sci 76:H175–H181. https://doi.org/10.1111/j.1750-3841.2011.02311.x

    Article  CAS  PubMed  Google Scholar 

  75. Deng C, Tao R, Yu SZ, Jin H (2012) Sulforaphane protects against 6-hydroxydopamine-induced cytotoxicity by increasing expression of heme oxygenase-1 in a PI3K/Akt-dependent manner. Mol Med Rep 5:847–851. https://doi.org/10.3892/mmr.2011.731

    Article  CAS  PubMed  Google Scholar 

  76. Benedict AL, Mountney A, Hurtado A, Bryan KE, Schnaar RL, Dinkova-Kostova AT, Talalay P (2012) Neuroprotective effects of sulforaphane after contusive spinal cord injury. J Neurotrauma 29:2576–2586. https://doi.org/10.1089/neu.2012.2474

    Article  PubMed  PubMed Central  Google Scholar 

  77. Kim HV, Kim HY, Ehrlich HY, Choi SY, Kim DJ, Kim Y (2013) Amelioration of Alzheimer’s disease by neuroprotective effect of sulforaphane in animal model. Amyloid 20:7–12. https://doi.org/10.3109/13506129.2012.751367

    Article  CAS  PubMed  Google Scholar 

  78. Ushida Y, Talalay P (2013) Sulforaphane accelerates acetaldehyde metabolism by inducing aldehyde dehydrogenases: relevance to ethanol intolerance. Alcohol Alcohol 48:526–534. https://doi.org/10.1093/alcalc/agt063

    Article  CAS  PubMed  Google Scholar 

  79. Zhou R, Lin J, Wu D (2014) Sulforaphane induces Nrf2 and protects against CYP2E1-dependent binge alcohol-induced liver steatosis. Biochim Biophys Acta 1840:209–218. https://doi.org/10.1016/j.bbagen.2013.09.018

    Article  CAS  PubMed  Google Scholar 

  80. Lin H, Wei B, Li G, Zheng J, Sun J, Chu J, Zeng R, Niu Y (2014) Sulforaphane reverses glucocorticoid-induced apoptosis in osteoblastic cells through regulation of the Nrf2 pathway. Drug Des Devel Ther 8:973–982. https://doi.org/10.2147/dddt.s65410

    Article  PubMed  PubMed Central  Google Scholar 

  81. Jiang X, Bai Y, Zhang Z, Xin Y, Cai L (2014) Protection by sulforaphane from type 1 diabetes-induced testicular apoptosis is associated with the up-regulation of Nrf2 expression and function. Toxicol Appl Pharmacol 279:198–210. https://doi.org/10.1016/j.taap.2014.06.009

    Article  CAS  Google Scholar 

  82. Lopes RA, Neves KB, Tostes RC, Montezano AC, Touyz RM (2015) Downregulation of nuclear factor erythroid 2-related factor and associated antioxidant genes contributes to redox-sensitive vascular dysfunction in hypertension. Hypertension 66:1240–1250. https://doi.org/10.1161/hypertensionaha.115.06163

    Article  CAS  PubMed  Google Scholar 

  83. Shirai Y, Fujita Y, Hashimoto R, Ohi K, Yamamori H, Yasuda Y, Ishima T, Suganuma H, Ushida Y, Takeda M, Hashimoto K (2015) Dietary intake of sulforaphane-rich broccoli sprout extracts during juvenile and adolescence can prevent phencyclidine-induced cognitive deficits at adulthood. PLoS One 10:e0127244. https://doi.org/10.1371/journal.pone.0127244

  84. Brown RH, Reynolds C, Brooker A, Talalay P, Fahey JW (2015) Sulforaphane improves the bronchoprotective response in asthmatics through Nrf2-mediated gene pathways. Respir Res 16:106. https://doi.org/10.1186/s12931-015-0253-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Dong Z, Shang H, Chen YQ, Pan LL, Bhatia M, Sun J (2016) Sulforaphane protects pancreatic acinar cell injury by modulating Nrf2-mediated oxidative stress and NLRP3 inflammatory pathway. Oxidative Med Cell Longev 2016:7864150. https://doi.org/10.1155/2016/7864150

    Article  CAS  Google Scholar 

  86. Kubo E, Chhunchha B, Singh P, Sasaki H, Singh DP (2017) Sulforaphane reactivates cellular antioxidant defense by inducing Nrf2/ARE/Prdx6 activity during aging and oxidative stress. Sci Rep 7:14130. https://doi.org/10.1038/s41598-017-14520-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Luo L, Chen Y, Wang H, Wang S, Liu K, Li X, Wang XJ, Tang X (2018) Mkp-1 protects mice against toxin-induced liver damage by promoting the Nrf2 cytoprotective response. Free Radic Biol Med 115:361–370. https://doi.org/10.1016/j.freeradbiomed.2017.12.010

    Article  CAS  PubMed  Google Scholar 

  88. Moriya K, SS, Furukawa M, Saikawa S, Namisaki T, Kitade M, Kawaratani H, Kaji K, Takaya H, Shimozato N, Sawada Y, Seki K, Kitagawa K, Akahane T, Mitoro A, Okura Y, Yoshiji H, Yamao J (2018) Sulforaphane inhibits liver cancer cell growth and angiogenesis. Arch Can Res 6. https://doi.org/10.21767/2254-6081.100189

  89. Liu P, Wang W, Tang J, Bowater RP, Bao Y (2019) Antioxidant effects of sulforaphane in human HepG2 cells and immortalised hepatocytes. Food Chem Toxicol 128:129–136. https://doi.org/10.1016/j.fct.2019.03.050

    Article  CAS  PubMed  Google Scholar 

  90. Khaleel SA, Raslan NA, Alzokaky AA, Ewees MG, Ashour AA, Abdel-Hamied HE, Abd-Allah AR (2019) Contrast media (meglumine diatrizoate) aggravates renal inflammation, oxidative DNA damage and apoptosis in diabetic rats which is restored by sulforaphane through Nrf2/HO-1 reactivation. Chem Biol Interact 309:108689. https://doi.org/10.1016/j.cbi.2019.06.002

    Article  CAS  PubMed  Google Scholar 

  91. Panda H, Keleku-Lukwete N, Kuga A, Fuke N, Suganuma H, Suzuki M, Yamamoto M (2019) Dietary supplementation with sulforaphane attenuates liver damage and heme overload in a sickle cell disease murine model. Exp Hematol 77:51–60.e1. https://doi.org/10.1016/j.exphem.2019.08.001

    Article  CAS  PubMed  Google Scholar 

  92. Moon JY, Kim DJ, Kim HS (2020) Sulforaphane ameliorates serum starvation-induced muscle atrophy via activation of the Nrf2 pathway in cultured C2C12 cells. Cell Biol Int 44:1831–1839. https://doi.org/10.1002/cbin.11377

    Article  CAS  PubMed  Google Scholar 

  93. Crichlow GV, Fan C, Keeler C, Hodsdon M, Lolis EJ (2012) Structural interactions dictate the kinetics of macrophage migration inhibitory factor inhibition by different cancer-preventive isothiocyanates. Biochemistry 51:7506–7514. https://doi.org/10.1021/bi3005494

    Article  CAS  PubMed  Google Scholar 

  94. Jain AD, Potteti H, Richardson BG, Kingsley L, Luciano JP, Ryuzoji AF, Lee H, Krunic A, Mesecar AD, Reddy SP, Moore TW (2015) Probing the structural requirements of non-electrophilic naphthalene-based Nrf2 activators. Eur J Med Chem 103:252–268. https://doi.org/10.1016/j.ejmech.2015.08.049

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Michalska P, Buendia I, Duarte P, Fernandez Mendivil C, Negredo P, Cuadrado A, López MG, Leon R (2020) Melatonin-sulforaphane hybrid ITH12674 attenuates glial response in vivo by blocking LPS binding to MD2 and receptor oligomerization. Pharmacol Res 152:104597. https://doi.org/10.1016/j.phrs.2019.104597

    Article  CAS  PubMed  Google Scholar 

  96. Wells G (2015) Peptide and small molecule inhibitors of the Keap1-Nrf2 protein-protein interaction. Biochem Soc Trans 43:674–679. https://doi.org/10.1042/bst20150051

    Article  CAS  PubMed  Google Scholar 

  97. Vaghefinezhad N, Farsani SF, Gharaghani S (2019) In silico drug-designing studies on sulforaphane analogues: pharmacophore mapping, molecular docking and QSAR modeling. Curr Drug Discov Technol. https://doi.org/10.2174/1570163816666191112122047

  98. Lestari ML, Indrayanto G (2014) Curcumin. Profiles Drug Subst Excip Relat Methodol 39:113–204. https://doi.org/10.1016/b978-0-12-800173-8.00003-9

    Article  CAS  PubMed  Google Scholar 

  99. Krishnaswamy K, Raghuramulu N (1998) Bioactive phytochemicals with emphasis on dietary practices. Indian J Med Res 108:167–181

    CAS  PubMed  Google Scholar 

  100. Zheng QT, Yang ZH, Yu LY, Ren YY, Huang QX, Liu Q, Ma XY, Chen ZK, Wang ZB, Zheng X (2017) Synthesis and antioxidant activity of curcumin analogs. J Asian Nat Prod Res 19:489–503. https://doi.org/10.1080/10286020.2016.1235562

    Article  CAS  PubMed  Google Scholar 

  101. Prasad S, Gupta SC, Tyagi AK, Aggarwal BB (2014) Curcumin, a component of golden spice: from bedside to bench and back. Biotechnol Adv 32:1053–1064. https://doi.org/10.1016/j.biotechadv.2014.04.004

    Article  CAS  PubMed  Google Scholar 

  102. Morita HAI, Noguchi H (2010) Plant type III PKS. Compr Nat Prod II Chem Biol 1:171–225

    Google Scholar 

  103. Santhoshkumar R, Yusuf A (2020) In silico structural modeling and analysis of physicochemical properties of curcumin synthase (CURS1, CURS2, and CURS3) proteins of Curcuma longa. J Genet Eng Biotechnol 18:24. https://doi.org/10.1186/s43141-020-00041-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Katsuyama Y, Kita T, Funa N, Horinouchi S (2009) Curcuminoid biosynthesis by two type III polyketide synthases in the herb Curcuma longa. J Biol Chem 284:11160–11170. https://doi.org/10.1074/jbc.M900070200

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. González-Albadalejo J, Sanz D, Claramunt R, Lavandera J-L, Alkorta I, Elguero J (2015) Curcumin and curcuminoids: chemistry, structural studies and biological properties. An Real Acad Farm 81:278–310

    Google Scholar 

  106. Siviero A, Gallo E, Maggini V, Gori L, Mugelli A, Firenzuoli F, Vannacci A (2015) Curcumin, a golden spice with a low bioavailability. J Herb Med 5:57–70. https://doi.org/10.1016/j.hermed.2015.03.001

    Article  Google Scholar 

  107. Zheng Q-T, Yang Z-H, Yu L-Y, Ren Y-Y, Huang Q-X, Liu Q, Ma X-Y, Chen Z-K, Wang Z-B, Zheng X (2017) Synthesis and antioxidant activity of curcumin analogs. J Asian Nat Prod Res 19:489–503. https://doi.org/10.1080/10286020.2016.1235562

    Article  CAS  PubMed  Google Scholar 

  108. Tsuda T (2018) Curcumin as a functional food-derived factor: degradation products, metabolites, bioactivity, and future perspectives. Food Funct 9:705–714. https://doi.org/10.1039/c7fo01242j

    Article  CAS  PubMed  Google Scholar 

  109. Aggarwal BB, Sundaram C, Malani N, Ichikawa H (2007) Curcumin: the Indian solid gold. Adv Exp Med Biol 595:1–75. https://doi.org/10.1007/978-0-387-46401-5_1

    Article  PubMed  Google Scholar 

  110. Kotha RR, Luthria DL (2019) Curcumin: biological, pharmaceutical, nutraceutical, and analytical aspects. Molecules 24. https://doi.org/10.3390/molecules24162930

  111. Dei Cas M, Ghidoni R (2019) Dietary curcumin: correlation between bioavailability and health potential. Nutrients 11. https://doi.org/10.3390/nu11092147

  112. Kuntz S, Kunz C, Domann E, Würdemann N, Unger F, Römpp A, Rudloff S (2016) Inhibition of low-grade inflammation by anthocyanins after microbial fermentation in vitro. Nutrients 8. https://doi.org/10.3390/nu8070411

  113. Bar-Sela G, Epelbaum R, Schaffer M (2010) Curcumin as an anti-cancer agent: review of the gap between basic and clinical applications. Curr Med Chem 17:190–197. https://doi.org/10.2174/092986710790149738

    Article  CAS  PubMed  Google Scholar 

  114. Krishnaswamy K, Orsat V (2017) Sustainable delivery systems through green nanotechnology. Nano- and Microscale Drug Delivery Systems 17–32. https://doi.org/10.1016/B978-0-323-52727-9.00002-9

  115. Yang KY, Lin LC, Tseng TY, Wang SC, Tsai TH (2007) Oral bioavailability of curcumin in rat and the herbal analysis from Curcuma longa by LC-MS/MS. J Chromatogr B Analyt Technol Biomed Life Sci 853:183–189. https://doi.org/10.1016/j.jchromb.2007.03.010

    Article  CAS  PubMed  Google Scholar 

  116. Gutierres VO, Campos ML, Arcaro CA, Assis RP, Baldan-Cimatti HM, Peccinini RG, Paula-Gomes S, Kettelhut IC, Baviera AM, Brunetti IL (2015) Curcumin pharmacokinetic and pharmacodynamic evidences in streptozotocin-diabetic rats support the antidiabetic activity to be via metabolite(s). Evid Based Complement Alternat Med 2015:678218. https://doi.org/10.1155/2015/678218

    Article  PubMed  PubMed Central  Google Scholar 

  117. Toden S, Goel A (2017) The holy grail of curcumin and its efficacy in various diseases: is bioavailability truly a big concern? J Restor Med 6:27-36. https://doi.org/10.14200/jrm.2017.6.0101

  118. Vareed SK, Kakarala M, Ruffin MT, Crowell JA, Normolle DP, Djuric Z, Brenner DE (2008) Pharmacokinetics of curcumin conjugate metabolites in healthy human subjects. Cancer Epidemiol Biomark Prev 17:1411–1417. https://doi.org/10.1158/1055-9965.Epi-07-2693

    Article  CAS  Google Scholar 

  119. Jamwal R (2018) Bioavailable curcumin formulations: a review of pharmacokinetic studies in healthy volunteers. J Integr Med 16:367–374. https://doi.org/10.1016/j.joim.2018.07.001

    Article  PubMed  Google Scholar 

  120. Stohs SJ, Chen O, Ray SD, Ji J, Bucci LR, Preuss HG (2020) Highly bioavailable forms of curcumin and promising avenues for curcumin-based research and application: a review. Molecules:25. https://doi.org/10.3390/molecules25061397

  121. Schiborr C, Kocher A, Behnam D, Jandasek J, Toelstede S, Frank J (2014) The oral bioavailability of curcumin from micronized powder and liquid micelles is significantly increased in healthy humans and differs between sexes. Mol Nutr Food Res 58:516–527. https://doi.org/10.1002/mnfr.201300724

    Article  CAS  PubMed  Google Scholar 

  122. Sasaki H, Sunagawa Y, Takahashi K, Imaizumi A, Fukuda H, Hashimoto T, Wada H, Katanasaka Y, Kakeya H, Fujita M, Hasegawa K, Morimoto T (2011) Innovative preparation of curcumin for improved oral bioavailability. Biol Pharm Bull 34:660–665. https://doi.org/10.1248/bpb.34.660

    Article  CAS  PubMed  Google Scholar 

  123. Paolino D, Vero A, Cosco D, Pecora TM, Cianciolo S, Fresta M, Pignatello R (2016) Improvement of oral bioavailability of curcumin upon microencapsulation with methacrylic copolymers. Front Pharmacol 7:485. https://doi.org/10.3389/fphar.2016.00485

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Sandhiutami N, Arozal W, Louisa M, Rahmat D, Mandy T (2019) Comparative effect of curcumin and nanocurcumin on nephroprotection at cisplatin-induced rats. J Pharm Bioallied Sci 11:567–573. https://doi.org/10.4103/jpbs.JPBS_208_19

    Article  Google Scholar 

  125. Jäger R, Lowery RP, Calvanese AV, Joy JM, Purpura M, Wilson JM (2014) Comparative absorption of curcumin formulations. Nutr J 13:11. https://doi.org/10.1186/1475-2891-13-11

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Gota VS, Maru GB, Soni TG, Gandhi TR, Kochar N, Agarwal MG (2010) Safety and pharmacokinetics of a solid lipid curcumin particle formulation in osteosarcoma patients and healthy volunteers. J Agric Food Chem 58:2095–2099. https://doi.org/10.1021/jf9024807

    Article  CAS  PubMed  Google Scholar 

  127. Lu PS, Inbaraj BS, Chen BH (2018) Determination of oral bioavailability of curcuminoid dispersions and nanoemulsions prepared from Curcuma longa Linnaeus. J Sci Food Agric 98:51–63. https://doi.org/10.1002/jsfa.8437

    Article  CAS  PubMed  Google Scholar 

  128. Seo SW, Han HK, Chun MK, Choi HK (2012) Preparation and pharmacokinetic evaluation of curcumin solid dispersion using Solutol® HS15 as a carrier. Int J Pharm 424:18–25. https://doi.org/10.1016/j.ijpharm.2011.12.051

    Article  CAS  PubMed  Google Scholar 

  129. Khalil NM (2013) Pharmacokinetics of curcumin-loaded PLGA and PLGA–PEG blend nanoparticles after oral administration in rats. Colloids Surf B Biointerfaces 101:353–360. https://doi.org/10.1016/j.colsurfb.2012.06.024

    Article  CAS  PubMed  Google Scholar 

  130. Di Meo F, Margarucci S, Galderisi U, Crispi S, Peluso G (2019) Curcumin, gut microbiota, and neuroprotection. Nutrients 11. https://doi.org/10.3390/nu11102426

  131. Ireson CR, Jones DJ, Orr S, Coughtrie MW, Boocock DJ, Williams ML, Farmer PB, Steward WP, Gescher AJ (2002) Metabolism of the cancer chemopreventive agent curcumin in human and rat intestine. Cancer Epidemiol Biomarkers Prev 11:105–111

    CAS  PubMed  Google Scholar 

  132. Heger M, van Golen RF, Broekgaarden M, Michel MC (2014) The molecular basis for the pharmacokinetics and pharmacodynamics of curcumin and its metabolites in relation to cancer. Pharmacol Rev 66:222–307. https://doi.org/10.1124/pr.110.004044

    Article  CAS  PubMed  Google Scholar 

  133. Jankun J, Wyganowska M, Dettlaff K, Jelińska A, Surdacka A, Wątr�bska-Świetlikowska D, Skrzypczak-Jankun E (2016) Determining whether curcumin degradation/condensation is actually bioactivation (review). Int J Mol Med 37. https://doi.org/10.3892/ijmm.2016.2524

  134. Pulido-Moran M, Moreno-Fernandez J, Ramirez-Tortosa C, Ramirez-Tortosa M (2016) Curcumin and health. Molecules 21:264. https://doi.org/10.3390/molecules21030264

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Gan C, Hu J, Nan D-D, Wang S, Li H (2017) Synthesis and biological evaluation of curcumin analogs as β-amyloid imaging agents. Future Med Chem 9:1587–1596. https://doi.org/10.4155/fmc-2017-0079

    Article  CAS  PubMed  Google Scholar 

  136. Liu Z, Dou W, Zheng Y, Wen Q, Qin M, Wang X, Tang H, Zhang R, Lv D, Wang J, Zhao S (2016) Curcumin upregulates Nrf2 nuclear translocation and protects rat hepatic stellate cells against oxidative stress. Mol Med Rep 13:1717–1724. https://doi.org/10.3892/mmr.2015.4690

    Article  CAS  PubMed  Google Scholar 

  137. Asouri MAR, Ahmadi AA, Amini A, Rezaei MM (2013) Antioxidant and free radical scavenging activities of curcumin. Asian J Chem 25:7593–7595

    Article  CAS  Google Scholar 

  138. Lee W-H, Loo C-Y, Bebawy M, Luk F, Mason RS, Rohanizadeh R (2013) Curcumin and its derivatives: their application in neuropharmacology and neuroscience in the 21st century. Curr Neuropharmacol 11:338–378. https://doi.org/10.2174/1570159x11311040002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  139. Meshkibaf MH, Maleknia M, Noroozi S (2019) Effect of curcumin on gene expression and protein level of methionine sulfoxide reductase A (MSRA), SOD, CAT and GPx in Freund’s adjuvant inflammation-induced male rats. J Inflamm Res 12:241–249. https://doi.org/10.2147/jir.S212577

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  140. Konigsberg M (2007) Nrf2: La historia de un nuevo factor de transcripción que responde a estrés oxidativo. Revista de Educación Bioquímica 26

    Google Scholar 

  141. González-Reyes S, Guzmán-Beltrán S, Medina-Campos ON, Pedraza-Chaverri J (2013) Curcumin pretreatment induces Nrf2 and an antioxidant response and prevents hemin-induced toxicity in primary cultures of cerebellar granule neurons of rats. Oxidative Med Cell Longev 2013:801418. https://doi.org/10.1155/2013/801418

    Article  Google Scholar 

  142. Lin X, Bai D, Wei Z, Zhang Y, Huang Y, Deng H, Huang X (2019) Curcumin attenuates oxidative stress in RAW264.7 cells by increasing the activity of antioxidant enzymes and activating the Nrf2-Keap1 pathway. PLoS One 14:e0216711. https://doi.org/10.1371/journal.pone.0216711

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  143. Zhao SG, Li Q, Liu ZX, Wang JJ, Wang XX, Qin M, Wen QS (2011) Curcumin attenuates insulin resistance in hepatocytes by inducing Nrf2 nuclear translocation. Hepato-Gastroenterology 58:2106–2111. https://doi.org/10.5754/hge11219

    Article  CAS  PubMed  Google Scholar 

  144. Qi L, Jiang J, Zhang J, Zhang L, Wang T (2020) Curcumin protects human trophoblast HTR8/SVneo cells from H(2)O(2)-induced oxidative stress by activating Nrf2 signaling pathway. Antioxidants (Basel) 9. https://doi.org/10.3390/antiox9020121

  145. Ren L, Zhan P, Wang Q, Wang C, Liu Y, Yu Z, Zhang S (2019) Curcumin upregulates the Nrf2 system by repressing inflammatory signaling-mediated Keap1 expression in insulin-resistant conditions. Biochem Biophys Res Commun 514:691–698. https://doi.org/10.1016/j.bbrc.2019.05.010

    Article  CAS  PubMed  Google Scholar 

  146. Kim J-S, Oh J-M, Choi H, Kim SW, Kim SW, Kim BG, Cho JH, Lee J, Lee DC (2020) Activation of the Nrf2/HO-1 pathway by curcumin inhibits oxidative stress in human nasal fibroblasts exposed to urban particulate matter. BMC Complement Med Therap 20:101. https://doi.org/10.1186/s12906-020-02886-8

    Article  CAS  Google Scholar 

  147. Guan THC, Huang Y, Li Y, Liu Y (2018) Effects of curcumin pretreatment on cell proliferation, oxidative stress, and Nrf2 pathways in HK-2 cells cultured in high glucose medium. Int J Clin Exp Med 11:13422–13428

    CAS  Google Scholar 

  148. Lee H, Kim S-W, Lee H-K, Luo L, Kim I-D, Lee J-K (2016) Upregulation of Nrf2–p300 mediates anti-inflammatory effects of curcumin in microglia by downregulating p65–p300. Animal Cells Syst 20:246–252. https://doi.org/10.1080/19768354.2016.1223169

  149. Lobo VPA, Phatak A, Chandra N (2010) Free radicals, antioxidants and functional foods: impact on human health. Pharmacogn Rev 4:118–126. https://doi.org/10.4103/0973-7847.70902

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  150. Hybertson BM, Gao B, Bose SK, JM MC (2011) Oxidative stress in health and disease: the therapeutic potential of Nrf2 activation. Mol Asp Med 32:234–246. https://doi.org/10.1016/j.mam.2011.10.006

    Article  CAS  Google Scholar 

  151. Deshmukh P, Unni S, Krishnappa G, Padmanabhan B (2017) The Keap1–Nrf2 pathway: promising therapeutic target to counteract ROS-mediated damage in cancers and neurodegenerative diseases. Biophys Rev 9:41–56. https://doi.org/10.1007/s12551-016-0244-4

    Article  CAS  PubMed  Google Scholar 

  152. Jaramillo MC, Zhang DD (2013) The emerging role of the Nrf2-Keap1 signaling pathway in cancer. Genes Develop 27:2179–2191. https://doi.org/10.1101/gad.225680.113

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  153. Liguori I, Russo G, Curcio F, Bulli G, Aran L, Della-Morte D, Gargiulo G, Testa G, Cacciatore F, Bonaduce D, Abete P (2018) Oxidative stress, aging, and diseases. Clin Interv Aging 13:757–772. https://doi.org/10.2147/cia.S158513

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  154. Ashrafizadeh M, Ahmadi Z, Mohammadinejad R, Farkhondeh T, Samarghandian S (2020) Curcumin activates the Nrf2 pathway and induces cellular protection against oxidative injury. Curr Mol Med 20:116–133. https://doi.org/10.2174/1566524019666191016150757

    Article  CAS  PubMed  Google Scholar 

  155. Asmat U, Abad K, Ismail K (2016) Diabetes mellitus and oxidative stress – a concise review. Saudi Pharmaceut J 24:547–553. https://doi.org/10.1016/j.jsps.2015.03.013

    Article  Google Scholar 

  156. Zhang P, Li T, Wu X, Nice EC, Huang C, Zhang YJFM (2020) Oxidative stress and diabetes: antioxidative strategies. Front Med 14:583–600

    Article  Google Scholar 

  157. David JA, Rifkin WJ, Rabbani PS, Ceradini DJ (2017) The Nrf2/Keap1/ARE pathway and oxidative stress as a therapeutic target in type II diabetes mellitus. J Diabetes Res 2017:4826724. https://doi.org/10.1155/2017/4826724

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  158. Uruno A, Yagishita Y, Yamamoto M (2015) The Keap1-Nrf2 system and diabetes mellitus. Arch Biochem Biophys 566:76–84. https://doi.org/10.1016/j.abb.2014.12.012

    Article  CAS  PubMed  Google Scholar 

  159. Jiménez-Osorio AS, González-Reyes S, Pedraza-Chaverri J (2015) Natural Nrf2 activators in diabetes. Clin Chim Acta 448:182–192. https://doi.org/10.1016/j.cca.2015.07.009

    Article  CAS  PubMed  Google Scholar 

  160. Sosa V, Moliné T, Somoza R, Paciucci R, Kondoh HMELL (2013) Oxidative stress and cancer: an overview. Ageing Res Rev 12:376–390. https://doi.org/10.1016/j.arr.2012.10.004

    Article  CAS  PubMed  Google Scholar 

  161. Hayes JDD-KA, Tew KD (2020) Oxidative stress in cancer. Cancer Cell. Cell Press 38:167–197

    Article  CAS  Google Scholar 

  162. Chen B, Zhang Y, Wang Y, Rao J, Jiang X, Xu Z (2014) Curcumin inhibits proliferation of breast cancer cells through Nrf2-mediated down-regulation of Fen1 expression. J Steroid Biochem Mol Biol 143:11–18. https://doi.org/10.1016/j.jsbmb.2014.01.009

    Article  CAS  PubMed  Google Scholar 

  163. Bellezza I, Mierla AL, Minelli A (2010) Nrf2 and NF-κB and their concerted modulation in cancer pathogenesis and progression. Cancers (Basel) 2:483–497. https://doi.org/10.3390/cancers2020483

    Article  CAS  Google Scholar 

  164. Das L, Vinayak M (2015) Long term effect of curcumin in restoration of tumour suppressor p53 and phase-II antioxidant enzymes via activation of Nrf2 signalling and modulation of inflammation in prevention of cancer. PLoS One 10:e0124000. https://doi.org/10.1371/journal.pone.0124000

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  165. Sporn MB, Liby KT (2012) NRF2 and cancer: the good, the bad and the importance of context. Nat Rev Cancer 12:564–571. https://doi.org/10.1038/nrc3278

    Article  CAS  PubMed  Google Scholar 

  166. Taguchi K, Yamamoto M (2017) The KEAP1–NRF2 system in: Cancer 7. https://doi.org/10.3389/fonc.2017.00085

  167. Zhou S, Sun W, Zhang Z, Zheng Y (2014) The role of Nrf2-mediated pathway in cardiac remodeling and heart failure. Oxidative Med Cell Longev 2014:260429. https://doi.org/10.1155/2014/260429

    Article  CAS  Google Scholar 

  168. Senoner T, Dichtl W (2019) Oxidative stress in cardiovascular diseases: still a therapeutic target? Nutrients 11. https://doi.org/10.3390/nu11092090

  169. Zeng C, Zhong P, Zhao Y, Kanchana K, Zhang Y, Khan ZA, Chakrabarti S, Wu L, Wang J, Liang G (2015) Curcumin protects hearts from FFA-induced injury by activating Nrf2 and inactivating NF-κB both in vitro and in vivo. J Mol Cell Cardiol 79:1–12. https://doi.org/10.1016/j.yjmcc.2014.10.002

    Article  CAS  PubMed  Google Scholar 

  170. Zang H, Mathew RO, Cui T (2020) The dark side of Nrf2 in the heart. Front Physiol 11:722. https://doi.org/10.3389/fphys.2020.00722

    Article  PubMed  PubMed Central  Google Scholar 

  171. Daenen K, Andries A, Mekahli D, Van Schepdael A, Jouret F, Bammens B (2019) Oxidative stress in chronic kidney disease. Pediatr Nephrol 34:975–991. https://doi.org/10.1007/s00467-018-4005-4

    Article  PubMed  Google Scholar 

  172. Ali BH, Al-Salam S, Al Suleimani Y, Al Kalbani J, Al Bahlani S, Ashique M, Manoj P, Al Dhahli B, Al Abri N, Naser HT, Yasin J, Nemmar A, Al Za’abi M, Hartmann C, Schupp N (2018) Curcumin ameliorates kidney function and oxidative stress in experimental chronic kidney disease. Basic Clin Pharmacol Toxicol 122:65–73. https://doi.org/10.1111/bcpt.12817

    Article  CAS  PubMed  Google Scholar 

  173. Choi BH, Kang KS, Kwak MK (2014) Effect of redox modulating NRF2 activators on chronic kidney disease. Molecules 19:12727–12759. https://doi.org/10.3390/molecules190812727

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  174. Ciccone L, Tepshi L, Nencetti S, Stura EA (2015) Transthyretin complexes with curcumin and bromo-estradiol: evaluation of solubilizing multicomponent mixtures. New Biotechnol 32:54–64. https://doi.org/10.1016/j.nbt.2014.09.002

    Article  CAS  Google Scholar 

  175. Banerjee S, Ji C, Mayfield JE, Goel A, Xiao J, Dixon JE, Guo X (2018) Ancient drug curcumin impedes 26S proteasome activity by direct inhibition of dual-specificity tyrosine-regulated kinase 2. Proc Natl Acad Sci U S A 115:8155–8160. https://doi.org/10.1073/pnas.1806797115

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  176. Shah AJ, Prasanth Kumar S, Rao MV, Pandya HA (2018) Ameliorative effects of curcumin towards cyclosporine-induced genotoxic potential: an in vitro and in silico study. Drug Chem Toxicol 41:259–269. https://doi.org/10.1080/01480545.2017.1380660

    Article  CAS  PubMed  Google Scholar 

  177. Kao Y-T, Chen Y-S, Tang K-W, Lee J-C, Tseng C-H, Tzeng C-C, Yen C-H, Chen Y-L (2020) Discovery of 4-anilinoquinolinylchalcone derivatives as potential NRF2 activators. Mol (Basel, Switzerland) 25. https://doi.org/10.3390/molecules25143133

  178. Rainone F (2005) Milk thistle. Am Fam Physician 72:1285–1288

    PubMed  Google Scholar 

  179. Abenavoli L, Capasso R, Milic N, Capasso F (2010) Milk thistle in liver diseases: past, present, future. Phytother Res 24:1423–1432. https://doi.org/10.1002/ptr.3207

    Article  CAS  PubMed  Google Scholar 

  180. Bijak M (2017) Silybin, a major bioactive component of milk thistle (Silybum marianum L. Gaernt.)-chemistry, bioavailability, and metabolism. Molecules 22. https://doi.org/10.3390/molecules22111942

  181. Biedermann D, Vavrikova E, Cvak L, Kren V (2014) Chemistry of silybin. Nat Prod Rep 31:1138–1157. https://doi.org/10.1039/c3np70122k

    Article  CAS  PubMed  Google Scholar 

  182. AbouZid SF, Chen SN, McAlpine JB, Friesen JB, Pauli GF (2016) Silybum marianum pericarp yields enhanced silymarin products. Fitoterapia 112:136–143. https://doi.org/10.1016/j.fitote.2016.05.012

  183. Javed S, Kohli K, Ali M (2011) Reassessing bioavailability of silymarin. Altern Med Rev 16:239–249

    PubMed  Google Scholar 

  184. Wu JW, Lin LC, Hung SC, Chi CW, Tsai TH (2007) Analysis of silibinin in rat plasma and bile for hepatobiliary excretion and oral bioavailability application. J Pharm Biomed Anal 45:635–641. https://doi.org/10.1016/j.jpba.2007.06.026

    Article  CAS  PubMed  Google Scholar 

  185. Lorenz D, Lucker PW, Mennicke WH, Wetzelsberger N (1984) Pharmacokinetic studies with silymarin in human serum and bile. Methods Find Exp Clin Pharmacol 6:655–661

    CAS  PubMed  Google Scholar 

  186. Yu JN, Zhu Y, Wang L, Peng M, Tong SS, Cao X, Qiu H, Xu XM (2010) Enhancement of oral bioavailability of the poorly water-soluble drug silybin by sodium cholate/phospholipid-mixed micelles. Acta Pharmacol Sin 31:759–764. https://doi.org/10.1038/aps.2010.55

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  187. Parveen R, Baboota S, Ali J, Ahuja A, Vasudev SS, Ahmad S (2011) Oil based nanocarrier for improved oral delivery of silymarin: in vitro and in vivo studies. Int J Pharm 413:245–253. https://doi.org/10.1016/j.ijpharm.2011.04.041

    Article  CAS  PubMed  Google Scholar 

  188. Wang Y, Zhang D, Liu Z, Liu G, Duan C, Jia L, Feng F, Zhang X, Shi Y, Zhang Q (2010) In vitro and in vivo evaluation of silybin nanosuspensions for oral and intravenous delivery. Nanotechnology 21:155104. https://doi.org/10.1088/0957-4484/21/15/155104

    Article  CAS  PubMed  Google Scholar 

  189. Jancova P, Siller M, Anzenbacherova E, Kren V, Anzenbacher P, Simanek V (2011) Evidence for differences in regioselective and stereoselective glucuronidation of silybin diastereomers from milk thistle (Silybum marianum) by human UDP-glucuronosyltransferases. Xenobiotica 41:743–751. https://doi.org/10.3109/00498254.2011.573017

    Article  CAS  PubMed  Google Scholar 

  190. Theodosiou E, Purchartová K, Stamatis H, Kolisis F, Vladimír, Kren (2014) Bioavility of silymarin flavonolignans: drug formulations and biotransformation. Phytochem Rev 12:1–18. https://doi.org/10.1007/s11101-013-9285-5

    Article  CAS  Google Scholar 

  191. Jancova P, Anzenbacherova E, Papouskova B, Lemr K, Luzna P, Veinlichova A, Anzenbacher P, Simanek V (2007) Silybin is metabolized by cytochrome P450 2C8 in vitro. Drug Metab Dispos 35:2035–2039. https://doi.org/10.1124/dmd.107.016410

    Article  CAS  PubMed  Google Scholar 

  192. Surai PF (2015) Silymarin as a natural antioxidant: an overview of the current evidence and perspectives. Antioxidants (Basel) 4:204–247. https://doi.org/10.3390/antiox4010204

    Article  CAS  Google Scholar 

  193. Jee SC, Kim M, Sung JS (2020) Modulatory effects of silymarin on benzo[a]pyrene-induced hepatotoxicity. Int J Mol Sci 21. https://doi.org/10.3390/ijms21072369

  194. Ahmed RF, Moussa RA, Eldemerdash RS, Zakaria MM, Abdel-Gaber SA (2019) Ameliorative effects of silymarin on HCl-induced acute lung injury in rats; role of the Nrf-2/HO-1 pathway. Iran J Basic Med Sci 22:1483–1492. https://doi.org/10.22038/IJBMS.2019.14069

    Article  PubMed  PubMed Central  Google Scholar 

  195. Kalthoff S, Strassburg CP (2019) Contribution of human UDP-glucuronosyltransferases to the antioxidant effects of propolis, artichoke and silymarin. Phytomedicine 56:35–39. https://doi.org/10.1016/j.phymed.2018.08.013

    Article  CAS  PubMed  Google Scholar 

  196. Abdelsalam HM, Samak MA, Alsemeh AE (2019) Synergistic therapeutic effects of Vitis vinifera extract and Silymarin on experimentally induced cardiorenal injury: the pertinent role of Nrf2. Biomed Pharmacother 110:37–46. https://doi.org/10.1016/j.biopha.2018.11.053

    Article  CAS  PubMed  Google Scholar 

  197. Valentova K, Purchartova K, Rydlova L, Roubalova L, Biedermann D, Petraskova L, Krenkova A, Pelantova H, Holeckova-Moravcova V, Tesarova E, Cvacka J, Vrba J, Ulrichova J, Kren V (2018) Sulfated metabolites of flavonolignans and 2,3-dehydroflavonolignans: preparation and properties. Int J Mol Sci 19. https://doi.org/10.3390/ijms19082349

  198. Liu Y, Yu Q, Chen Y (2018) Effect of silibinin on CFLAR-JNK pathway in oleic acid-treated HepG2 cells. Biomed Pharmacother 108:716–723. https://doi.org/10.1016/j.biopha.2018.09.089

    Article  CAS  PubMed  Google Scholar 

  199. Ou Q, Weng Y, Wang S, Zhao Y, Zhang F, Zhou J, Wu X (2018) Silybin alleviates hepatic steatosis and fibrosis in NASH mice by inhibiting oxidative stress and involvement with the Nf-kappaB pathway. Dig Dis Sci 63:3398–3408. https://doi.org/10.1007/s10620-018-5268-0

    Article  CAS  PubMed  Google Scholar 

  200. Arafa Keshk W, Zahran SM, Katary MA, Abd-Elaziz Ali D (2017) Modulatory effect of silymarin on nuclear factor-erythroid-2-related factor 2 regulated redox status, nuclear factor-kappaB mediated inflammation and apoptosis in experimental gastric ulcer. Chem Biol Interact 273:266–272. https://doi.org/10.1016/j.cbi.2017.06.022

    Article  CAS  PubMed  Google Scholar 

  201. Li L, Sun HY, Liu W, Zhao HY, Shao ML (2017) Silymarin protects against acrylamide-induced neurotoxicity via Nrf2 signalling in PC12 cells. Food Chem Toxicol 102:93–101. https://doi.org/10.1016/j.fct.2017.01.021

    Article  CAS  PubMed  Google Scholar 

  202. Al-Rasheed N, Faddah L, Al-Rasheed N, Bassiouni YA, Hasan IH, Mahmoud AM, Mohamad RA, Yacoub HI (2016) Protective effects of silymarin, alone or in combination with chlorogenic acid and/or melatonin, against carbon tetrachloride-induced hepatotoxicity. Pharmacogn Mag 12:S337–S345. https://doi.org/10.4103/0973-1296.185765

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  203. Roubalova L, Dinkova-Kostova AT, Biedermann D, Kren V, Ulrichova J, Vrba J (2017) Flavonolignan 2,3-dehydrosilydianin activates Nrf2 and upregulates NAD(P)H:quinone oxidoreductase 1 in Hepa1c1c7 cells. Fitoterapia 119:115–120. https://doi.org/10.1016/j.fitote.2017.04.012

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  204. Zhou J, Chao G, Li Y, Wu M, Zhong S, Feng Z (2016) Activation of NRF2/ARE by isosilybin alleviates a beta 25-35-induced oxidative stress injury in HT-22 cells. Neurosci Lett 632:92–97. https://doi.org/10.1016/j.neulet.2016.08.043

    Article  CAS  PubMed  Google Scholar 

  205. Vargas-Mendoza N, Morales-González Á, Morales-Martínez M, Soriano-Ursúa MA, Delgado-Olivares L, Sandoval-Gallegos EM, Madrigal-Bujaidar E, Álvarez-González I, Madrigal-Santillán E, Morales-Gonzalez JA (2020) Flavolignans from silymarin as Nrf2 bioactivators and their therapeutic applications. Biomedicine 8. https://doi.org/10.3390/biomedicines8050122

  206. Li M, Huang W, Jie F, Wang M, Zhong Y, Chen Q, Lu B (2019) Discovery of Keap1-Nrf2 small-molecule inhibitors from phytochemicals based on molecular docking. Food Chem Toxicol 133:110758. https://doi.org/10.1016/j.fct.2019.110758

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  207. Heightman TD, Callahan JF, Chiarparin E, Coyle JE, Griffiths-Jones C, Lakdawala AS, McMenamin R, Mortenson PN, Norton D, Peakman TM, Rich SJ, Richardson C, Rumsey WL, Sanchez Y, Saxty G, Willems HMG, Wolfe L 3rd, Woolford AJ, Wu Z, Yan H, Kerns JK, Davies TG (2019) Structure-activity and structure-conformation relationships of aryl propionic acid inhibitors of the kelch-like ECH-associated protein 1/Nuclear factor erythroid 2-related factor 2 (KEAP1/NRF2) protein-protein interaction. J Med Chem 62:4683–4702. https://doi.org/10.1021/acs.jmedchem.9b00279

  208. Tran K, Pallesen J, Solbak S, Narayanan D, Baig A, Zang J, Aguayo A, Carmona R, Garcia A, Bach A (2019) A comparative assessment study of known small-molecule Keap1-Nrf2 protein-protein interaction inhibitors: chemical synthesis, binding properties, and cellular activity. J Med Chem 62. https://doi.org/10.1021/acs.jmedchem.9b00723

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Authors and Affiliations

  1. Laboratorio de Medicina de Conservación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Mexico City, Mexico

    Nancy Vargas-Mendoza, Eduardo O. Madrigal-Santillán, Marcelo Angeles-Valencia, Jacqueline Portillo-Reyes & José Antonio Morales-González

  2. Centro de Investigación Interdisciplinario, Área Académica de Nutrición, Instituto de Ciencias de la Salud, Universidad Autónoma del Estado de Hidalgo, Pachuca, Mexico

    Eli Mireya Sandoval-Gallegos

  3. Licenciatura en Nutrición, Universidad Intercontinental, Mexico City, Mexico

    Mauricio Morales-Martínez

  4. Academia de Fisiología Humana, Escuela Superior de Medicina, Instituto Politécnico Nacional, Mexico City, Mexico

    Marvin Antonio Soriano-Ursúa

  5. Escuela Superior de Cómputo, Instituto Politécnico Nacional, Mexico City, Mexico

    Ángel Morales-González

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  1. Nancy Vargas-Mendoza
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  7. Ángel Morales-González
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  9. José Antonio Morales-González
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Correspondence to José Antonio Morales-González .

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  1. Department of Pharmaceutical Botany, Jagiellonian University, Medical College, Kraków, Poland

    Halina Maria Ekiert

  2. Department of Botany, Mohanlal Sukhadia University, Udaipur, India

    Kishan Gopal Ramawat

  3. Department of Botany, Mohanlal Sukhadia University, Udaipur, India

    Jaya Arora

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  1. Department of Pharmaceutical Botany, Jagiellonian University, Collegium Medicum, Kraków, Poland

    Halina Ekiert

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Vargas-Mendoza, N. et al. (2022). The Cytoprotective Activity of Nrf2 Is Regulated by Phytochemicals (Sulforaphane, Curcumin, and Silymarin). In: Ekiert, H.M., Ramawat, K.G., Arora, J. (eds) Plant Antioxidants and Health. Reference Series in Phytochemistry. Springer, Cham. https://doi.org/10.1007/978-3-030-78160-6_34

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