Isothiocyanates are promising compounds against oxidative stress, neuroinflammation and cell death that may benefit neurodegeneration in Parkinson’s disease

International Journal of Molecular Sciences

Volumn 17, Issue 9, 2016, Pages

  Sita, Giulia ^a   Hrelia, Patrizia ^a   Tarozzi, Andrea ^a   Morroni, Fabiana ^a  

^a UNIVERSITY OF BOLOGNA   (Italy)

Author keywords

Isothiocyanates; Neuroinflammation; Neuroprotection; NrF2 pathway; Oxidative stress; Parkinson s disease

Indexed keywords

4 IODOPHENYL ISOTHIOCYANATE; 6 (METHYLSULFINYL) HEXYL ISOTHIOCYANATE; ERUCIN; GLIAL FIBRILLARY ACIDIC PROTEIN; GLUTATHIONE; HLA D ANTIGEN; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INDUCIBLE NITRIC OXIDE SYNTHASE; INTERLEUKIN 1BETA; ISOTHIOCYANATE 3; ISOTHIOCYANIC ACID; ISOTHIOCYANIC ACID DERIVATIVE; NITRIC OXIDE SYNTHASE; PHENETHYL ISOTHIOCYANATE; REACTIVE OXYGEN METABOLITE; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE OXIDASE; SULFORAPHANE; TRANSCRIPTION FACTOR NRF2; TUMOR NECROSIS FACTOR; UNCLASSIFIED DRUG; ANTIINFLAMMATORY AGENT; ANTIOXIDANT; KELCH LIKE ECH ASSOCIATED PROTEIN 1; NEUROPROTECTIVE AGENT; PLANT EXTRACT;

APOPTOSIS; ASTROCYTE; BRASSICA; CELL CYCLE REGULATION; CELL DEATH; CELL INFILTRATION; CHAPERONE-MEDIATED AUTOPHAGY; DOPAMINERGIC NERVE CELL; DRUG MECHANISM; EXCITOTOXICITY; HUMAN; INFLAMMATION; MICROGLIA; NERVE DEGENERATION; NERVOUS SYSTEM INFLAMMATION; NONHUMAN; OXIDATIVE STRESS; PARKINSON DISEASE; REVIEW; SIGNAL TRANSDUCTION; SUBSTANTIA NIGRA; T LYMPHOCYTE; ANIMAL; DRUG EFFECTS; GENETICS; METABOLISM; NERVE CELL;

ANIMALS; ANTI-INFLAMMATORY AGENTS; ANTIOXIDANTS; HUMANS; ISOTHIOCYANATES; KELCH-LIKE ECH-ASSOCIATED PROTEIN 1; NEURONS; NEUROPROTECTIVE AGENTS; PARKINSON DISEASE; PLANT EXTRACTS;

EID: 85016105532     PISSN: 16616596     EISSN: 14220067     Source Type: Journal    
DOI: 10.3390/ijms17091454     Document Type: Review

References (130)

1. Barbosa, M.; Valentão, P.; Andrade, P.B. Bioactive compounds from macroalgae in the new millennium: Implications for neurodegenerative diseases. Mar. Drugs 2014, 12, 4934–4972.
2. Dauer, W.; Przedborski, S. Parkinson’s disease: Mechanisms and models. Neuron 2003, 39, 889–909.
3. Lull, M.E.; Block, M.L. Microglial Activation and Chronic Neurodegeneration. Neurotherapeutics 2010, 7, 354–365.
4. Vidal, R.; Matus, S.; Bargsted, L.; Hetz, C. Targeting autophagy in neurodegenerative diseases. Trends Pharmacol. Sci. 2014, 35, 583–591.
5. Litvan, I.; Halliday, G.; Hallett, M.; Goetz, C.G.; Rocca, W.; Duyckaerts, C.; Ben-shlomo, Y.; Dickson, D.W.; Lang, A.E.; Chesselet, M. et al. The Etiopathogenesis of Parkinson Disease and Suggestions for Future Research. Part I. J. Neuropathol. Exp. Neurol. 2007, 66, 251–257.
6. Esposito, E.; Cuzzocrea, S. New therapeutic strategy for Parkinson’s and Alzheimer’s disease. Curr. Med. Chem. 2010, 17, 2764–2774.
7. Allan, S.; Rothwell, N. Citokines and acute neurodegeneration. Nat. Rev. Neurosci. 2001, 2, 734–744.
8. Del Zoppo, G.J.; Becker, K.J.; Hallenbeck, J.M. Inflammation after stroke: Is it harmful? Arch. Neurol. 2001, 58, 669–672.
9. Novío, S.; Cartea, M.E.; Soengas, P.; Freire-Garabal, M.; Núñez-Iglesias, M.J. Effects of Brassicaceae Isothiocyanates on Prostate Cancer. Molecules 2016, 21, E626.
10. De Figueiredo, S.M.; Binda, N.S.; Nogueira-Machado, J.A.; Vieira-Filho, S.A.; Caligiorne, R.B. The antioxidant properties of organosulfur compounds (sulforaphane). Recent Pat. Endocr. Metab. Immune Drug Discov. 2015, 9, 24–39.
11. Kumar, H.; Kim, I.-S.; More, S.V.; Kim, B.-W.; Choi, D.-K. Natural product-derived pharmacological modulators of Nrf2/ARE pathway for chronic diseases. Nat. Prod. Rep. 2014, 31, 109–139.
12. Heiss, E.; Herhaus, C.; Klimo, K.; Bartsch, H.; Gerhäuser, C. Nuclear factor B is a molecular target for sulforaphane-mediated anti-inflammatory mechanisms. J. Biol. Chem. 2001, 276, 32008–32015.
13. Minarini, A.; Milelli, A.; Fimognari, C.; Simoni, E.; Turrini, E.; Tumiatti, V. Exploring the effects of isothiocyanates on chemotherapeutic drugs. Expert Opin. Drug Metab. Toxicol. 2014, 10, 25–38.
14. Wu, L.; Noyan Ashraf, M.H.; Facci, M.; Wang, R.; Paterson, P.G.; Ferrie, A.; Juurlink, B.H.J. Dietary approach to attenuate oxidative stress, hypertension, and inflammation in the cardiovascular system. Proc. Natl. Acad. Sci. USA 2004, 101, 7094–7099.
15. Senanayake, G.V.K.; Banigesh, A.; Wu, L.; Lee, P.; Juurlink, B.H.J. The dietary phase 2 protein inducer sulforaphane can normalize the kidney epigenome and improve blood pressure in hypertensive rats. Am. J. Hypertens. 2012, 25, 229–235.
16. Mukherjee, S.; Gangopadhyay, H.; Das, D.K. Broccoli: A unique vegetable that protects mammalian hearts through the redox cycling of the thioredoxin superfamily. J. Agric. Food Chem. 2008, 56, 609–617.
17. Morroni, F.; Sita, G.; Tarozzi, A.; Cantelli-Forti, G.; Hrelia, P. Neuroprotection by 6-(methylsulfinyl)hexyl isothiocyanate in a 6-hydroxydopamine mouse model of Parkinson’s disease. Brain Res. 2014, 1589, 93–104.
18. Morroni, F.; Tarozzi, A.; Sita, G.; Bolondi, C.; Zolezzi Moraga, J.M.; Cantelli-Forti, G.; Hrelia, P. Neuroprotective effect of sulforaphane in 6-hydroxydopamine-lesioned mouse model of Parkinson’s disease. Neurotoxicology 2013, 36, 63–71.
19. Kerns, M.L.; DePianto, D.; Dinkova-Kostova, A.T.; Talalay, P.; Coulombe, P.A. Reprogramming of keratin biosynthesis by sulforaphane restores skin integrity in epidermolysis bullosa simplex. Proc. Natl. Acad. Sci. USA 2007, 104, 14460–14465.
20. Savitt, J.; Dawson, V.; Dawson, T. Diagnosis and treatment of Parkinson disease: Molecules to medicine. J. Clin. Investig. 2006, 116, 1744–1754.
21. Spillantini, M.; Schmidt, M.; Lee, V.; Trojanowski, J.; Jakes, R.; Goedert, M. -Synuclein in Lewy bodies. Nature 1997, 388, 839–840.
22. Vingerhoets, G.; Verleden, S.; Santens, P.; Miatton, M.; de Reuck, J. Predictors of cognitive impairment in advanced Parkinson’s disease. J. Neurol. Neurosurg. Psychiatry 2003, 74, 793–796.
23. Sung, V.W.; Nicholas, A.P. Nonmotor symptoms in parkinson’s disease. Expanding the view of Parkinson’s disease beyond a pure motor, pure dopaminergic problem. Neurol. Clin. 2013, 31, S1–S16.
24. Francardo, V.; Recchia, A.; Popovic, N.; Andersson, D.; Nissbrandt, H.; Cenci, M.A. Impact of the lesion procedure on the profiles of motor impairment and molecular responsiveness to L-DOPA in the 6-hydroxydopamine mouse model of Parkinson’s disease. Neurobiol. Dis. 2011, 42, 327–340.
25. Dias, V.; Junn, E.; Mouradian, M.M. The role of oxidative stress in Parkinson’s disease. J. Parkinsons Dis. 2013, 3, 461–491.
26. Trachootham, D.; Lu, W.; Ogasawara, M.A.; Nilsa, R.-D.V.; Huang, P. Redox regulation of cell survival. Antioxid. Redox Signal. 2008, 10, 1343–1374.
27. Jones, D.P.; Go, Y.M. Redox compartmentalization and cellular stress. Diabetes Obes. Metab. 2010, 12, 116–125.
28. Jenner, P.; Olanow, C.W. The pathogenesis of cell death in Parkinson’s disease. Neurology 2006, 66, S24–S36.
29. Wahner, A.D.; Bronstein, J.M.; Bordelon, Y.M.; Ritz, B. Nonsteroidal anti-inflammatory drugs may protect against Parkinson disease. Neurology 2007, 69, 1836–1842.
30. Dong, X.; Wang, Y.; Qin, Z. Molecular mechanisms of excitotoxicity and their relevance to pathogenesis of neurodegenerative diseases. Acta Pharmacol. Sin. 2009, 30, 379–387.
31. Kountouras, J.; Zavos, C.; Polyzos, S.A.; Deretzi, G.; Vardaka, E.; Giartza-Taxidou, E.; Katsinelos, P.; Rapti, E.; Chatzopoulos, D.; Tzilves, D. et al. Helicobacter pylori infection and Parkinson’s disease: Apoptosis as an underlying common contributor. Eur. J. Neurol. 2012, 19, e56.
32. Kannan, K.; Jain, S. Oxidative stress and apoptosis. Pathophysiology 2000, 7, 153–163.
33. Jellinger, K.A. Cell death mechanisms in Parkinson’s disease. J. Neural Transm. 2000, 107, 1–29.
34. Stojkovska, I.; Wagner, B.M.; Morrison, B.E. Parkinson’s disease and enhanced inflammatory response. Exp. Biol. Med. 2015, 240, 1387–1395.
35. Perry, V.; Bell, M.; Brown, H.; Matyszak, M. Inflammation in the nervous system. Curr. Opin. Neurobiol. 1995, 5, 636–641.
36. Barone, F.C.; Feuerstein, G.Z. Inflammatory Mediators and Stroke: New Opportunities for Novel Therapeutics. J. Cereb. Blood Flow Metab. 1999, 19, 819–834.
37. Glass, C.K.; Saijo, K.; Winner, B.; Marchetto, M.C.; Gage, F.H. Mechanisms underlying inflammation in neurodegeneration. Cell 2010, 140, 918–934.
38. Sanchez-Guajardo, V.; Febbraro, F.; Kirik, D.; Romero-Ramos, M. Microglia acquire distinct activation profiles depending on the degree of -synuclein neuropathology in a rAAV based model of Parkinson’s disease. PLoS ONE 2010, 5, e8784.
39. McGeer, P.; Itagaki, S.; Boyes, B.; McGeer, E. Reactive microglia are positive for HLA-DR in the substantia nigra of Parkinson’s and Alzheimer’s disease brains. Neurology 1988, 38, 1285–1291.
40. Tansey, M.G.; McCoy, M.K.; Frank-Cannon, T.C. Neuroinflammatory mechanisms in Parkinson’s disease: Potential environmental triggers, pathways, and targets for early therapeutic intervention. Exp. Neurol. 2007, 208, 1–25.
41. Chen, H.; Zhang, S.M.; Hernán, M.A.; Schwarzschild, M.A.; Willett, W.C.; Colditz, G.A.; Speizer, F.E.; Ascherio, A. Nonsteroidal anti-inflammatory drugs and the risk of Parkinson disease. Arch. Neurol. 2003, 60, 1059–1064.
42. Song, I.-U.; Kim, Y.-D.; Cho, H.-J.; Chung, S.-W. Is Neuroinflammation Involved in the Development of Dementia in Patients with Parkinson’s Disease? Intern. Med. 2013, 52, 1787–1792.
43. Hirsch, E.C.E.; Hunot, S. Neuroinflammation in Parkinson’s disease: A target for neuroprotection? Lancet Neurol. 2009, 8, 382–397.
44. More, S.V.; Kumar, H.; Kim, I.S.; Song, S.-Y.; Choi, D.-K. Cellular and molecular mediators of neuroinflammation in the pathogenesis of Parkinson’s disease. Mediat. Inflamm. 2013, 2013, 952375.
45. Lucin, K.M.; Wyss-Coray, T. Immune activation in brain aging and neurodegeneration: Too much or too little? Neuron 2009, 64, 110–122.
46. Tobin, M.K.; Bonds, J.A.; Minshall, R.D.; Pelligrino, D.A.; Testai, F.D.; Lazarov, O. Neurogenesis and inflammation after ischemic stroke: What is known and where we go from here. J. Cereb. Blood Flow Metab. 2014, 34, 1573–1584.
47. Gerhard, A.; Pavese, N.; Hotton, G.; Turkheimer, F.; Es, M.; Hammers, A.; Eggert, K.; Oertel, W.; Banati, R.B.; Brooks, D.J. In vivo imaging of microglial activation with [11C](R)-PK11195 PET in idiopathic Parkinson’s disease. Neurobiol. Dis. 2006, 21, 404–412.
48. Kohutnicka, M.; Lewandowska, E.; Kurkowska-Jastrzebska, I.; Członkowski, A.; Członkowska, A. Microglial and astrocytic involvement in a murine model of Parkinson’s disease induced by 1-methyl-4- phenyl-1,2,3,6-tetrahydropyridine (MPTP). Immunopharmacology 1998, 39, 167–180.
49. McLaughlin, P.; Zhou, Y.; Ma, T.; Liu, J.; Zhang, W.; Hong, J.-S.; Kovacs, M.; Zhang, J. Proteomic analysis of microglial contribution to mouse strain-dependent dopaminergic neurotoxicity. Glia 2006, 53, 567–582.
50. Mogi, M.; Harada, M.; Narabayashi, H.; Inagaki, H.; Minami, M.; Nagatsu, T. Interleukin (IL)-1 β, IL-2, IL-4, IL-6 and transforming growth factor- levels are elevated in ventricular cerebrospinal fluid in juvenile parkinsonism and Parkinson’s disease. Neurosci. Lett. 1996, 211, 13–16.
51. Koppula, S.; Kumar, H.; Kim, I.S.; Choi, D.-K. Reactive oxygen species and inhibitors of inflammatory enzymes, NADPH oxidase, and iNOS in experimental models of Parkinson’s disease. Mediat. Inflamm. 2012, 2012, 823902.
52. Bechmann, I.; Galea, I.; Perry, V. What is the blood-brain barrier (not)? Trends Immunol. 2007, 28, 5–11.
53. Rappold, P.; Tieu, K. Astrocytes and therapeutics for Parkinson’s disease. Neurotherapeutics 2010, 7, 413–423.
54. Wu, D.; Tieu, K.; Cohen, O.; Choi, D.; Vila, M.; Jackson-Lewis, V.; Teismann, P.; Przedborski, S. Glial cell response: A pathogenic factor in Parkinson’s disease. J. Neurovirol. 2002, 8, 551–558.
55. Damier, P.; Hirsch, E.C.; Zhang, P.; Agid, Y.; Javoy-Agid, F. Glutathione peroxidase, glial cells and Parkinson’s disease. Neuroscience 1993, 52, 1–6.
56. Halliday, G.M.; Stevens, C.H. Glia: Initiators and progressors of pathology in Parkinson’s disease. Mov. Disord. 2011, 26, 6–17.
57. Ben Haim, L.; Carrillo-de Sauvage, M.-A.; Ceyzériat, K.; Escartin, C. Elusive roles for reactive astrocytes in neurodegenerative diseases. Front. Cell. Neurosci. 2015, 9, 278.
58. Chao, Y.; Wong, S.C.; Tan, E.K. Evidence of inflammatory system involvement in Parkinson’s disease. BioMed Res. Int. 2014, 2014, 308654.
59. Mosley, R.L.; Hutter-Saunders, J.A.; Stone, D.K.; Gendelman, H.E. Inflammation and adaptive immunity in Parkinson’s disease. Cold Spring Harb. Perspect. Med. 2012, 2, a009381.
60. Benner, E.J.; Banerjee, R.; Reynolds, A.D.; Sherman, S.; Pisarev, V.M.; Tsiperson, V.; Nemachek, C.; Ciborowski, P.; Przedborski, S.; Mosley, R.L. et al. Nitrated -synuclein immunity accelerates degeneration of nigral dopaminergic neurons. PLoS ONE 2008, 3, e1376.
61. Mecocci, P.; Tinarelli, C.; Schulz, R.J.; Polidori, M.C. Nutraceuticals in cognitive impairment and Alzheimer’s disease. Front. Pharmacol. 2014, 5, 147.
62. Pedras, M.S.C.; Yaya, E.E. Phytoalexins from Brassicaceae: News from the front. Phytochemistry 2010, 71, 1191–1197.
63. Kapusta-Duch, J.; Kopeć, A.; Piatkowska, E.; Borczak, B.; Leszczyńska, T. The beneficial effects of Brassica vegetables on human health. Rocz. Państwowego Zakładu Hig. 2012, 63, 389–395.
64. Verkerk, R.; Schreiner, M.; Krumbein, A.; Ciska, E.; Holst, B.; Rowland, I.; de Schrijver, R.; Hansen, M.; Gerhäuser, C.; Mithen, R. et al. Glucosinolates in Brassica vegetables: The influence of the food supply chain on intake, bioavailability and human health. Mol. Nutr. Food Res. 2009, 53 (Suppl. 2), S219.
65. Bones, A.M.; Rossiter, J.T. The enzymic and chemically induced decomposition of glucosinolates. Phytochemistry 2006, 67, 1053–1067.
66. Hara, M.; Eto, H.; Kuboi, T. Tissue printing for myrosinase activity in roots of turnip and Japanese radish and horseradish: A technique for localizing myrosinases. Plant Sci. 2001, 160, 425–431.
67. Ishida, M.; Hara, M.; Fukino, N.; Kakizaki, T.; Morimitsu, Y. Glucosinolate metabolism, functionality and breeding for the improvement of Brassicaceae vegetables. Breed. Sci. 2014, 64, 48–59.
68. Nguyen, T.; Sherratt, P.J.; Nioi, P.; Yang, C.S.; Pickett, C.B. Nrf2 controls constitutive and inducible expression of ARE-driven genes through a dynamic pathway involving nucleocytoplasmic shuttling by Keap1. J. Biol. Chem. 2005, 280, 32485–32492.
69. Drobnica, L.; Kristian, P. The Chemistry of the -NCS Group; Patai, S., Ed.; John Wiley & Sons: Hoboken, NJ, USA, 1977.
70. Zhang, Y.; Kolm, R.H.; Mannervik, B.; Talalay, P. Reversible conjugation of isothiocyanates with glutathione catalyzed by human glutathione transferases. Biochem. Biophys. Res. Commun. 1995, 206, 748–755.
71. Itoh, K.; Wakabayashi, N.; Katoh, Y.; Ishii, T.; Igarashi, K.; Engel, J.D.; Yamamoto, M. Keap1 represses nuclear activation of antioxidant responsive elements by Nrf2 through binding to the amino-terminal Neh2 domain. Genes Dev. 1999, 13, 76–86.
72. Baird, L.; Dinkova-Kostova, A.T. The cytoprotective role of the Keap1-Nrf2 pathway. Arch. Toxicol. 2011, 85, 241–272.
73. Pall, M.L.; Levine, S. Nrf2, a master regulator of detoxification and also antioxidant, anti-inflammatory and other cytoprotective mechanisms, is raised by health promoting factors. Sheng Li Xue Bao 2015, 67, 1–18.
74. Johnson, J.A.; Johnson, D.A.; Kraft, A.D.; Calkins, M.J.; Jakel, R.J.; Vargas, M.R.; Chen, P.-C. The Nrf2-ARE pathway: An indicator and modulator of oxidative stress in neurodegeneration. Ann. N. Y. Acad. Sci. 2008, 1147, 61–69.
75. Ramos-Gomez, M.; Kwak, M.K.; Dolan, P.M.; Itoh, K.; Yamamoto, M.; Talalay, P.; Kensler, T.W. Sensitivity to carcinogenesis is increased and chemoprotective efficacy of enzyme inducers is lost in Nrf2 transcription factor-deficient mice. Proc. Natl. Acad. Sci. USA 2001, 98, 3410–3415.
76. Ganesh Yerra, V.; Negi, G.; Sharma, S.S.; Kumar, A. Potential therapeutic effects of the simultaneous targeting of the Nrf2 and NF-B pathways in diabetic neuropathy. Redox Biol. 2013, 1, 394–397.
77. Barone, M.C.; Sykiotis, G.P.; Bohmann, D. Genetic activation of Nrf2 signaling is sufficient to ameliorate neurodegenerative phenotypes in a Drosophila model of Parkinson’s disease. Dis. Model. Mech. 2011, 4, 701–707.
78. Zhang, Z.; Cui, W.; Li, G.; Yuan, S.; Xu, D.; Hoi, M.P.M.; Lin, Z.; Dou, J.; Han, Y.; Lee, S.M.Y. Baicalein protects against 6-OHDA-induced neurotoxicity through activation of Keap1/Nrf2/HO-1 and involving PKC and PI3K/AKT signaling pathways. J. Agric. Food Chem. 2012, 60, 8171–8182.
79. Jakel, R.J.; Townsend, J.A.; Kraft, A.D.; Johnson, J.A. Nrf2-Mediated protection against 6-hydroxydopamine. Brain Res. 2007, 1144, 192–201.
80. Innamorato, N.G.; Jazwa, A.; Rojo, A.I.; García, C.; Fernández-Ruiz, J.; Grochot-Przeczek, A.; Stachurska, A.; Jozkowicz, A.; Dulak, J.; Cuadrado, A. Different susceptibility to the Parkinson’s toxin MPTP in mice lacking the redox master regulator Nrf2 or its target gene heme oxygenase-1. PLoS ONE 2010, 5, e11838.
81. Loboda, A.; Damulewicz, M.; Pyza, E.; Jozkowicz, A.; Dulak, J. Role of Nrf2/HO-1 system in development, oxidative stress response and diseases: An evolutionarily conserved mechanism. Cell. Mol. Life Sci. 2016, 73, 1–27.
82. Ben-Neriah, Y.; Karin, M. Inflammation meets cancer, with NF-B as the matchmaker. Nat. Immunol. 2011, 12, 715–723.
83. Wardyn, J.; Ponsford, A.; Sanderson, C. Dissecting molecular cross-talk between Nrf2 and NF-B response pathways. Biochem. Soc. Trans. 2015, 43, 621–626.
84. Rushworth, S.A.; Zaitseva, L.; Murray, M.Y.; Shah, N.M.; Bowles, K.M.; MacEwan, D.J. The high Nrf2 expression in human acute myeloid leukemia is driven by NF-B and underlies its chemo-resistance. Blood 2012, 120, 5188–5198.
85. Liu, G.G.-H.; Qu, J.; Shen, X. NF-B/p65 antagonizes Nrf2-ARE pathway by depriving CBP from Nrf2 and facilitating recruitment of HDAC3 to MafK. Biochim. Biophys. Acta 2008, 1783, 713–727.
86. Jiang, T.; Tian, F.; Zheng, H.; Whitman, S.A.; Lin, Y.; Zhang, Z.; Zhang, N.; Zhang, D.D. Nrf2 suppresses lupus nephritis through inhibition of oxidative injury and the NF-B-mediated inflammatory response. Kidney Int. 2014, 85, 333–343.
87. Innamorato, N.G.; Rojo, A.I.; García-Yagüe, A.J.; Yamamoto, M.; de Ceballos, M.L.; Cuadrado, A. The transcription factor Nrf2 is a therapeutic target against brain inflammation. J. Immunol. 2008, 181, 680–689.
88. Pawate, S.; Shen, Q.; Fan, F.; Bhat, N.R. Redox regulation of glial inflammatory response to lipopolysaccharide and interferongamma. J. Neurosci. Res. 2004, 77, 540–551.
89. Ghosh, S.; Hayden, M.S. New regulators of NF-B in inflammation. Nat. Rev. Immunol. 2008, 8, 837–848.
90. Dinkova-Kostova, A.T.; Talalay, P. Direct and indirect antioxidant properties of inducers of cytoprotective proteins. Mol. Nutr. Food Res. 2008, 52 (Suppl. 1), S128–S138.
91. Brandenburg, L.-O.; Kipp, M.; Lucius, R.; Pufe, T.; Wruck, C.J. Sulforaphane suppresses LPS-induced inflammation in primary rat microglia. Inflamm. Res. 2009, 59, 443–450.
92. McWalter, G.K.; Higgins, L.G.; McLellan, L.I.; Henderson, C.J.; Song, L.; Thornalley, P.J.; Itoh, K.; Yamamoto, M.; Hayes, J.D. 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. 2004, 134, 3499S–3506S.
93. Han, J.M.; Lee, Y.J.; Lee, S.Y.; Kim, E.M.; Moon, Y.; Kim, H.W.; Hwang, O. Protective effect of sulforaphane against dopaminergic cell death. J. Pharmacol. Exp. Ther. 2007, 321, 249–256.
94. Galuppo, M.; Iori, R.; De Nicola, G.; Bramanti, P.; Mazzon, E. Anti-Inflammatory and anti-apoptotic effects of (RS)-glucoraphanin bioactivated with myrosinase in murine sub-acute and acute MPTP-induced Parkinson’s disease. Bioorg. Med. Chem. 2013, 21, 5532–5547.
95. Jazwa, A.; Rojo, A.I.; Innamorato, N.G.; Hesse, M.; Fernández-Ruiz, J.; Cuadrado, A. Pharmacological targeting of the transcription factor Nrf2 at the basal ganglia provides disease modifying therapy for experimental parkinsonism. Antioxid. Redox Signal. 2011, 14, 2347–2360.
96. Kim, D.; You, B.; Jo, E.-K.; Han, S.-K.; Simon, M.I.; Lee, S.J. NADPH oxidase 2-derived reactive oxygen species in spinal cord microglia contribute to peripheral nerve injury-induced neuropathic pain. Proc. Natl. Acad. Sci. USA 2010, 107, 14851–14856.
97. Lin, W.; Wu, R.; 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, 967–973.
98. Wang, H.; Khor, T.O.; Saw, C.L.L.; Lin, W.; Wu, T.; Huang, Y.; Kong, A.-N.T. Role of Nrf2 in suppressing LPS-induced inflammation in mouse peritoneal macrophages by polyunsaturated fatty acids docosahexaenoic acid and eicosapentaenoic acid. Mol. Pharm. 2010, 7, 2185–2193.
99. Tarozzi, A.; Morroni, F.; Merlicco, A.; Hrelia, S.; Angeloni, C.; Cantelli-Forti, G.; Hrelia, P. Sulforaphane as an inducer of glutathione prevents oxidative stress-induced cell death in a dopaminergic-like neuroblastoma cell line. J. Neurochem. 2009, 111, 1161–1171.
100. Deng, C.; Tao, R.; Yu, S.-Z.; Jin, H. Sulforaphane protects against 6-hydroxydopamine-induced cytotoxicity by increasing expression of heme oxygenase-1 in a PI3K/Akt-dependent manner. Mol. Med. Rep. 2012, 5, 847–851.
101. Deng, C.; Tao, R.; Yu, S.-Z.; Jin, H. Inhibition of 6-hydroxydopamine-induced endoplasmic reticulum stress by sulforaphane through the activation of Nrf2 nuclear translocation. Mol. Med. Rep. 2012, 6, 215–219.
102. Vauzour, D.; Buonfiglio, M.; Corona, G.; Chirafisi, J.; Vafeiadou, K.; Angeloni, C.; Hrelia, S.; Hrelia, P.; Spencer, J.P.E. Sulforaphane protects cortical neurons against 5-S-cysteinyl-dopamine-induced toxicity through the activation of ERK1/2, Nrf-2 and the upregulation of detoxification enzymes. Mol. Nutr. Food Res. 2010, 54, 532–542.
103. Giacoppo, S.; Galuppo, M.; Montaut, S.; Iori, R.; Rollin, P.; Bramanti, P.; Mazzon, E. An overview on neuroprotective effects of isothiocyanates for the treatment of neurodegenerative diseases. Fitoterapia 2015, 106, 12–21.
104. Dwivedi, S.; Rajasekar, N.; Hanif, K.; Nath, C.; Shukla, R. Sulforaphane Ameliorates Okadaic Acid-Induced Memory Impairment in Rats by Activating the Nrf2/HO-1 Antioxidant Pathway. Mol. Neurobiol. 2015.
105. Clarke, J.D.; Riedl, K.; Bella, D.; Schwartz, S.J.; Stevens, J.F.; Ho, E. Comparison of isothiocyanate metabolite levels and histone deacetylase activity in human subjects consuming broccoli sprouts or broccoli supplement. J. Agric. Food Chem. 2011, 59, 10955–10963.
106. Hanlon, N.; Coldham, N.; Sauer, M.J.; Ioannides, C. Up-Regulation of the CYP1 family in rat and human liver by the aliphatic isothiocyanates erucin and sulforaphane. Toxicology 2008, 252, 92–98.
107. Hanlon, N.; Coldham, N.; Sauer, M.J.; Ioannides, C. Modulation of rat pulmonary carcinogen-metabolising enzyme systems by the isothiocyanates erucin and sulforaphane. Chem. Biol. Interact. 2009, 177, 115–120.
108. Melchini, A.; Traka, M.H. Biological profile of erucin: A new promising anticancer agent from cruciferous vegetables. Toxins 2010, 2, 593–612.
109. Yehuda, H.; Soroka, Y.; Zlotkin-Frušić, M.; Gilhar, A.; Milner, Y.; Tamir, S. Isothiocyanates inhibit psoriasis-related proinflammatory factors in human skin. Inflamm. Res. 2012, 61, 735–742.
110. Cho, H.J.; Lee, K.W.; Park, J.H.Y. Erucin exerts anti-inflammatory properties in murine macrophages and mouse skin: Possible mediation through the inhibition of NFB signaling. Int. J.Mol. Sci. 2013, 14, 20564–20577.
111. Wagner, A.; Sturm, C.; Piegholdt, S.; Wolf, I.; Esatbeyoglu, T.; De Nicola, G.; Iori, R.; Rimbach, G. Myrosinase-treated glucoerucin is a potent inducer of the Nrf2 target gene heme oxygenase 1—Studies in cultured HT-29 cells and mice. J. Nutr. Biochem. 2015, 26, 661–666.
112. Tarozzi, A.; Morroni, F.; Bolondi, C.; Sita, G.; Hrelia, P.; Djemil, A.; Cantelli-Forti, G. Neuroprotective effects of erucin against 6-hydroxydopamine-induced oxidative damage in a dopaminergic-like neuroblastoma cell line. Int. J. Mol. Sci. 2012, 13, 10899–10910.
113. Eklind, K.I.; Morse, M.A.; Chung, F.L. Distribution and metabolism of the natural anticarcinogen phenethyl isothiocyanate in A/J mice. Carcinogenesis 1990, 11, 2033–2036.
114. Ji, Y.; Morris, M.E.; Ji, Y.; Morris, M.E.M.E.; Ji, Y.; Morris, M.E. Determination of phenethyl isothiocyanate in human plasma and urine by ammonia derivatization and liquid chromatography-tandem mass spectrometry. Anal. Biochem. 2003, 323, 39–47.
115. Zhang, Y.; Talalay, P. Anticarcinogenic activities of organic isothiocyanates: Chemistry and mechanisms. Cancer Res. 1994, 54, 1976s–1981s.
116. Hecht, S.S. Chemoprevention by isothiocyanates. J. Cell. Biochem. Suppl. 1995, 22, 195–209.
117. Rose, P.; Won, Y.K.Y.; Ong, C.N.C.; Whiteman, M. β-Phenylethyl and 8-methylsulphinyloctyl isothiocyanates, constituents of watercress, suppress LPS induced production of nitric oxide and prostaglandin E2 in RAW 264.7 macrophages. Nitric Oxide 2005, 12, 237–243.
118. Adesida, A.; Edwards, L.; Thornalley, P. Inhibition of human leukaemia 60 cell growth by mercapturic acid metabolites of phenylethyl isothiocyanate. Food Chem. Toxicol. 1996, 34, 385–392.
119. Qin, C.-Z.; Zhang, X.; Wu, L.-X.; Wen, C.-J.; Hu, L.; Lv, Q.-L.; Shen, D.-Y.; Zhou, H.-H. Advances in molecular signaling mechanisms of β-phenethyl isothiocyanate antitumor effects. J. Agric. Food Chem. 2015, 63, 3311–3322.
120. Dey, M.; Ribnicky, D.; Kurmukov, A.G.; Raskin, I. In vitro and in vivo anti-inflammatory activity of a seed preparation containing phenethylisothiocyanate. J. Pharmacol. Exp. Ther. 2006, 317, 326–333.
121. Park, H.; Kim, S.; Park, S.; Eom, S.; Gu, G.; Kim, S.; Youn, H. Phenethyl isothiocyanate regulates inflammation through suppression of the TRIF-dependent signaling pathway of Toll-like receptors. Life Sci. 2013, 92, 793–798.
122. Boyanapalli, S.S.S.; Paredes-gonzalez, X.; Fuentes, F.; Zhang, C.; Guo, Y.; Pung, D.; Lay, C.; Saw, L.; Kong, A.T. Nrf2 Knockout Attenuates the Anti-Inflammatory Effects of Phenethyl Isothiocyanate and Curcumin. Chem. Res. Toxicol. 2014, 27, 2036–2043.
123. Uto, T.; Hou, D.-X.; Morinaga, O.; Shoyama, Y. Molecular Mechanisms Underlying Anti-Inflammatory Actions of 6-(Methylsulfinyl)hexyl Isothiocyanate Derived fromWasabi (Wasabia japonica). Adv. Pharmacol. Sci. 2012, 2012, 614046.
124. Uto, T.; Fujii, M.; Hou, D.-X. Inhibition of lipopolysaccharide-induced cyclooxygenase-2 transcription by 6-(methylsulfinyl) hexyl isothiocyanate, a chemopreventive compound from Wasabia japonica (Miq.) Matsumura, in mouse macrophages. Biochem. Pharmacol. 2005, 70, 1772–1784.
125. Noshita, T.; Kidachi, Y.; Funayama, H.; Kiyota, H.; Yamaguchi, H.; Ryoyama, K. Anti-nitric oxide production activity of isothiocyanates correlates with their polar surface area rather than their lipophilicity. Eur. J. Med. Chem. 2009, 44, 4931–4936.
126. Chen, J.; Uto, T.; Tanigawa, S.; Yamada-Kato, T.; Fujii, M.; Hou, D.-X. Microarray-based determination of anti-inflammatory genes targeted by 6-(methylsulfinyl)hexyl isothiocyanate in macrophages. Exp. Ther. Med. 2010, 1, 33–40.
127. Morimitsu, Y.; Nakagawa, Y.; Hayashi, K.; Fujii, H.; Kumagai, T.; Nakamura, Y.; Osawa, T.; Horio, F.; Itoh, K.; Iida, K. et al. A sulforaphane analogue that potently activates the Nrf2-dependent detoxification pathway. J. Biol. Chem. 2002, 277, 3456–3463.
128. Mizuno, K.; Kume, T.; Muto, C.; Takada-Takatori, Y.; Izumi, Y.; Sugimoto, H.; Akaike, A. Glutathione biosynthesis via activation of the nuclear factor E2-related factor 2 (Nrf2)—Antioxidant-response element (ARE) pathway is essential for neuroprotective effects of sulforaphane and 6-(methylsulfinyl) hexyl isothiocyanate. J. Pharmacol. Sci. 2011, 115, 320–328.
129. Lee, J.A.; Son, H.J.; Park, K.D.; Han, S.H.; Shin, N.; Kim, J.H.; Kim, H.R.; Kim, D.J.; Hwang, O. A Novel Compound ITC-3 Activates the Nrf2 Signaling and Provides Neuroprotection in Parkinson’s Disease Models. Neurotox. Res. 2015, 28, 332–345.
130. Wellejus, A.; Elbrønd-Bek, H.; Kelly, N.M.; Weidner, M.S.; Jørgensen, S.H. 4-Iodophenyl isothiocyanate: A neuroprotective compound. Restor. Neurol. Neurosci. 2012, 30, 21–38.