NeuroMolecular Medicine

, 10:236 | Cite as

Hormetic Dietary Phytochemicals

  • Tae Gen Son
  • Simonetta CamandolaEmail author
  • Mark P. Mattson
Review Paper


Compelling evidence from epidemiological studies suggests beneficial roles of dietary phytochemicals in protecting against chronic disorders such as cancer, and inflammatory and cardiovascular diseases. Emerging findings suggest that several dietary phytochemicals also benefit the nervous system and, when consumed regularly, may reduce the risk of disorders such as Alzheimer’s and Parkinson’s diseases. The evidence supporting health benefits of vegetables and fruits provide a rationale for identification of the specific phytochemicals responsible, and for investigation of their molecular and cellular mechanisms of action. One general mechanism of action of phytochemicals that is emerging from recent studies is that they activate adaptive cellular stress response pathways. From an evolutionary perspective, the noxious properties of such phytochemicals play an important role in dissuading insects and other pests from eating the plants. However at the subtoxic doses ingested by humans that consume the plants, the phytochemicals induce mild cellular stress responses. This phenomenon has been widely observed in biology and medicine, and has been described as ‘preconditioning’ or ‘hormesis.’ Hormetic pathways activated by phytochemicals may involve kinases and transcription factors that induce the expression of genes that encode antioxidant enzymes, protein chaperones, phase-2 enzymes, neurotrophic factors, and other cytoprotective proteins. Specific examples of such pathways include the sirtuin–FOXO pathway, the NF-κB pathway, and the Nrf-2/ARE pathway. In this article, we describe the hormesis hypothesis of phytochemical actions with a focus on the Nrf2/ARE signaling pathway as a prototypical example of a neuroprotective mechanism of action of specific dietary phytochemicals.


Nrf2 Antioxidant response element Hormesis Sirtuin Stress Sulforaphane Resveratrol 


  1. Aggarwal, B. B., & Ichikawa, H. (2005). Molecular targets and anticancer potential of indole-3-carbinol and its derivatives. Cell Cycle, 9, 1201–1215.Google Scholar
  2. Akihisa, T., Tokuda, H., Ukiya, M., et al. (2003). Chalcones, coumarins, and flavanones from the exudate of Angelica keiskei and their chemopreventive effects. Cancer Letters, 201, 133–137.PubMedGoogle Scholar
  3. Alcaraz, M. J., Vicente, A. M., & Araico, A. (2004). Role of nuclear factor-kappaB and heme oxygenase-1 in the mechanism of action of an anti-inflammatory chalcone derivative in RAW 264.7 cells. British Journal of Pharmacology, 142, 1191–1199.PubMedGoogle Scholar
  4. Ames, B. N., Profet, M., & Gold, L. S. (1990). Dietary pesticides (99.99% all natural). Proceedings of the National Academy of Sciences of the United States of America, 87, 7777–7781.PubMedGoogle Scholar
  5. Araico, A., Terencio, M. C., & Alcaraz, M. J. (2006). Phenylsulphonyl urenyl chalcone derivatives as dual inhibitors of cyclo-oxygenase-2 and 5-lipoxygenase. Life Sciences, 78, 2911–2918.PubMedGoogle Scholar
  6. Araki, T., Sasaki, Y., & Milbrandt, J. (2004). Increased nuclear NAD biosynthesis and SIRT1 activation prevent axonal degeneration. Science, 305, 1010–1013.PubMedGoogle Scholar
  7. Asanoma, M., Takahashi, K., Miyabe, M., et al. (1993). Inhibitory effect of topical application of polymerized ferulic acid, a synthetic lignin, on tumor promotion in mouse skin two stage tumorigenesis. Carcinogenesis, 14, 1321–1325.Google Scholar
  8. Ban, H. S., Suzuki, K., & Lim, S. S. (2004). Inhibition of lipopolysaccharide-induced expression of inducible nitric oxide synthase and tumor necrosis factor-alpha by 2’-hydroxychalcone derivatives in RAW 264.7 cells. Biochemical Pharmacology, 67, 1549–1557.PubMedGoogle Scholar
  9. Bastianetto, S., Yao, Z. X., Papadopoulos, V., & Quirion, R. (2006). Neuroprotective effects of green and black teas and their catechin gallate esters against beta-amyloid-induced toxicity. European Journal of Neuroscience, 23, 55–64.PubMedGoogle Scholar
  10. Bastianetto, S., Zheng, W. H., & Quirion, R. (2000). Neuroprotective abilities of resveratrol and other red wine constituents against nitric oxide-related toxicity in cultured hippocampal neurons. British Journal of Pharmacology, 131, 711–720.PubMedGoogle Scholar
  11. Bendich, A., & Langseth, L. (1989). Safety of vitamin A. American Journal of Clinical Nutrition, 49, 358–371.PubMedGoogle Scholar
  12. Berger, K. J., & Guss, D. A. (2005). Mycotoxins revisited: Part I. Journal of Emergency Medicine, 28, 53–62.PubMedGoogle Scholar
  13. Brunet, A., Sweeney, L. B., Sturgill, J. F., Chua, K. F., et al. (2004). Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase. Science, 303, 2011–2015.PubMedGoogle Scholar
  14. Calabrese, E. J., Bachmann, K. A., Bailer, A. J., Bolger, P. M., Borak, J., et al. (2007). Biological stress response terminology: Integrating the concepts of adaptive response and preconditioning stress within a hormetic dose-response framework. Toxicology and Applied Pharmacology, 222, 122–128.PubMedGoogle Scholar
  15. Camandola, S., & Mattson, M. P. (2007). NF-kappa B as a therapeutic target in neurodegenerative diseases. Expert Opinion on Therapeutic Targets, 11, 123–132.PubMedGoogle Scholar
  16. Carlson, D. G., Daxenbichler, M. E., VanEtten, C. H., Tookey, H. L., & Williams, P. H. (1981). Glucosinolates in crucifer vegetables: turnips and rutabagas. Journal of Agricultural and Food Chemistry, 29, 1235–1239.PubMedGoogle Scholar
  17. Cavin, C., Holzhaeuser, D., Scharf, G., et al. (2002). Cafestol and kahweol, two coffee specific diterpenes with anticarcinogenic activity. Food and Chemical Toxicology, 8, 1155–1163.Google Scholar
  18. Chen, C., Pung, D., Leong, V., Hebbar, V., et al. (2004). Induction of detoxifying enzymes by garlic organosulfur compounds through transcription factor Nrf2: Effect of chemical structure and stress signals. Free Radical Biology and Medicine, 37, 1578–1590.PubMedGoogle Scholar
  19. Cook, R., & Calabrese, E. J. (2007). The importance of hormesis to public health. Ciência & Saúde Coletiva, 12, 955–963.Google Scholar
  20. Dajas, F., Rivera, F., Blasina, F., Arredondo, F., et al. (2003). Cell culture protection and in vivo neuroprotective capacity of flavonoids. Neurotoxicity Research, 5, 425–432.PubMedCrossRefGoogle Scholar
  21. Dinkova-Kostova, A. T., Holtzclaw, W. D., Cole, R. N., Itoh, K., et al. (2002). Direct evidence that sulfhydryl groups of Keap1 are the sensors regulating induction of phase 2 enzymes that protect against carcinogens and oxidants. Proceedings of the National Academy of Sciences of the United States of America, 99, 11908–11913.PubMedGoogle Scholar
  22. Ehrnhoefer, D. E., Duennwald, M., Markovic, P., Wacker, J. L., Engemann, S., et al. (2006). Green tea (-)-epigallocatechin-gallate modulates early events in huntingtin misfolding and reduces toxicity in Huntington’s disease models. Human Molecular Genetics, 15, 2743–2751.PubMedGoogle Scholar
  23. Farombi, E. O., Shrotriya, S., Na, H. K., et al. (2008). Curcumin attenuates dimethylnitrosamine-induced liver injury in rats through Nrf2-mediated induction of heme oxygenase-1. Food and Chemical Toxicology, 46, 1279–1287.PubMedGoogle Scholar
  24. Ferrigni, N. R., McLaughlin, J. L., Powell, R. G., & Smith, C. R., Jr. (1984). Use of potato disc and brine shrimp bioassays to detect activity and isolate piceatannol as the antileukemic principle from the seeds of Euphorbia lagascae. Journal of Natural Products, 47, 347–352.PubMedGoogle Scholar
  25. Fontana, L., & Klein, S. (2007). Aging, adiposity, and calorie restriction. The Journal of the American Medical Association, 297, 986–994.Google Scholar
  26. Foresti, R., Hoque, M., Monti, D., Green, C. J., & Motterlini, R. (2005). Differential activation of heme oxygenase-1 by chalcones and rosolic acid in endothelial cells. Journal of Pharmacology and Experimental Therapeutics, 312, 686–693.PubMedGoogle Scholar
  27. Frescas, D., Valenti, L., & Accili, D. (2005). Nuclear trapping of the forkhead transcription factor FoxO1 via Sirt-dependent deacetylation promotes expression of glucogenetic genes. Journal of Biological Chemistry, 280, 20589–20595.PubMedGoogle Scholar
  28. Gong, P., Hu, B., & Cederbaum, A. I. (2004). Diallyl sulfide induces heme oxygenase-1 through MAPK pathway. Archives of Biochemistry and Biophysics, 432, 252–260.PubMedGoogle Scholar
  29. Gopalakrishnan, A., & Tony Kong, A. N. (2008). Anticarcinogenesis by dietary phytochemicals: Cytoprotection by Nrf2 in normal cells and cytotoxicity by modulation of transcription factors NF-kappaB and AP-1 in abnormal cancer cells. Food and Chemical Toxicology, 46, 1257–1270.PubMedGoogle Scholar
  30. Gopalakrishnan, A., Xu, C. J., Nair, S. S., Chen, C., et al. (2006). Modulation of activator protein-1 (AP-1) and MAPK pathway by flavonoids in human prostate cancer PC3 cells. Archives of Pharmacal Research, 8, 633–644.Google Scholar
  31. Guo, S., Yan, J., Yang, T., Yang, X., Bezard, E., & Zhao, B. (2007). Protective effects of green tea polyphenols in the 6-OHDA rat model of Parkinson’s disease through inhibition of ROS-NO pathway. Biological Psychiatry, 62, 1353–1362.PubMedGoogle Scholar
  32. Han, J. M., Lee, Y. J., Lee, S. Y., Kim, E. M., et al. (2007). Protective effect of sulforaphane against dopaminergic cell death. Journal of Pharmacology and Experimental Therapeutics, 321, 249–256.PubMedGoogle Scholar
  33. Haque A. M., Hashimoto M., Katakura M., Hara Y., & Shido O. (2008) Green tea catechins prevent cognitive deficits caused by Abeta(1-40) in rats. Journal of Nutritional Biochemistry. Feb 14; [Epub. Ahead of print].Google Scholar
  34. Hathcock, J. N., Hattan, D. G., Jenkins, M. Y., McDonald, J. T., Sundaresan, P. R., & Wilkening, V. L. (1990). Evaluation of vitamin A toxicity. American Journal of Clinical Nutrition, 52, 183–202.PubMedGoogle Scholar
  35. Hayek, T., Fuhrman, B., Vaya, J., et al. (1997). Reduced progression of atherosclerosis in apolipoprotein E-deficient mice following consumption of red wine, or its polyphenols quercetin or catechin, is associated with reduced susceptibility of LDL to oxidation and aggregation. Arteriosclerosis, Thrombosis, and Vascular Biology, 17, 2744–2752.PubMedGoogle Scholar
  36. Hayes, D. P. (2007). Nutritional hormesis. European Journal of Clinical Nutrition, 61, 147–159.PubMedGoogle Scholar
  37. Heber, D. (2004). Vegetables, fruits and phytoestrogens in the prevention of diseases. Journal of Postgraduate Medicine, 50, 145–149.PubMedGoogle Scholar
  38. Hu, R., Xu, C., Shen, G., Jain, M. R., et al. (2006a). Identification of Nrf2-regulated genes induced by chemopreventive isothiocyanate PEITC by oligonucleotide microarray. Life Sciences, 79, 1944–1955.PubMedGoogle Scholar
  39. Hu, R., Xu, C., Shen, G., Jain, M. R., et al. (2006b). Gene expression profiles induced by cancer chemopreventive isothiocyanate sulforaphane in the liver of C57BL/6 J mice and C57BL/6 J/Nrf2 (-/-) mice. Cancer Letters, 243, 170–192.PubMedGoogle Scholar
  40. Huang, Y. T., Hwang, J. J., Lee, P. P., Ke, F. C., et al. (1999). Effects of luteolin and quercetin, inhibitors of tyrosine kinase, on cell growth and metastasis-associated properties in A431 cells overexpressing epidermal growth factor receptor. British Journal of Pharmacology, 128, 999–1010.PubMedGoogle Scholar
  41. Huffman, M. A. (2003). Animal self-medication and ethno-medicine: Exploration and exploitation of the medicinal properties of plants. Proceedings of the Nutrition Society, 62, 371–381.PubMedGoogle Scholar
  42. Isman, M. B. (2006). The role of botanical insecticides, deterrents and repellents in modern agriculture and an increasingly regulated world. Annual Review of Entomology, 51, 45–66.PubMedGoogle Scholar
  43. Jagetia, G. C., & Aggarwal, B. B. (2007). “Spicing up” of the immune system by curcumin. Journal of Clinical Immunology, 27, 19–35.PubMedGoogle Scholar
  44. Jang, J. H., & Surh, Y. J. (2003). Protective effect of resveratrol on beta-amyloid-induced oxidative PC12 cell death. Free Radical Biology and Medicine, 34, 1100–1110.PubMedGoogle Scholar
  45. Jeong, W. S., Keum, Y. S., Chen, C., Jain, M. R., et al. (2005). Differential expression and stability of endogenous nuclear factor E2-related factor 2 (Nrf2) by natural chemopreventive compounds in HepG2 human hepatoma cells. Journal of Biochemistry and Molecular Biology, 38, 167–176.PubMedGoogle Scholar
  46. Jiao, D., Eklind, K. I., Choi, C. I., Desai, D. H., Amin, S. G., & Chung, F. L. (1994). Structure-activity relationships of isothiocyanates as mechanism-based inhibitors of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced lung tumorigenesis in A/J mice. Cancer Research, 54, 4327–4333.PubMedGoogle Scholar
  47. Jin, C. Y., Moon, D. O., Lee, K. J., Kim, M. O., et al. (2006). Piceatannol attenuates lipopolysaccharide-induced NF-kappaB activation and NF-kappaB-related proinflammatory mediators in BV2 microglia. Pharmacological Research, 54, 461–467.PubMedGoogle Scholar
  48. Joseph, J. A., Denisova, N. A., Arendash, G., Gordon, M., et al. (2003). Blueberry supplementation enhances signaling and prevents behavioral deficits in an Alzheimer disease model. Nutritional Neuroscience, 6, 153–162.PubMedGoogle Scholar
  49. Joseph, J. A., Shukitt-Hale, B., & Casadesus, G. (2005). Reversing the deleterious effects of aging on neuronal communication and behavior: Beneficial properties of fruit polyphenolic compounds. American Journal of Clinical Nutrition, 81(1 Suppl), 313S–316S.PubMedGoogle Scholar
  50. Joseph, J. A., Shukitt-Hale, B., Denisova, N. A., Bielinski, D., et al. (1999). Reversals of age-related declines in neuronal signal transduction, cognitive, and motor behavioral deficits with blueberry, spinach, or strawberry dietary supplementation. Journal of Neuroscience, 19, 8114–8121.PubMedGoogle Scholar
  51. Juge, N., Mithen, R. F., & Traka, M. (2007). Molecular basis for chemoprevention by sulforaphane: A comprehensive review. Cellular and Molecular Life Sciences, 9, 1105–1127.Google Scholar
  52. Katula, K. S., McCain, J. A., & Radewicz, A. T. (2005). Relative ability of dietary compounds to modulate nuclear factor-kappaB activity as assessed in a cell-based reporter system. Journal of Medicinal Food, 8, 269–274.PubMedGoogle Scholar
  53. Kawabata, K., Yamamoto, T., Hara, A., et al. (2000). Modifying effects of ferulic acid on azoxymethane-induced colon carcinogenesis in F344 rats. Cancer Letters, 157, 15–21.PubMedGoogle Scholar
  54. Kim, H. S., Cho, J. Y., Kim, D. H., et al. (2004). Inhibitory effects of long term administration of ferulic acid on microglial activation induced by intercerebroventricular injection of beta-amyloid peptide (1–42) in mice. Biological and Pharmaceutical Bulletin, 27, 120–121.PubMedGoogle Scholar
  55. Kim, H. J., Lee, K. W., & Lee, H. J. (2007). Protective effects of piceatannol against beta-amyloid-induced neuronal cell death. Annals of the New York Academy of Sciences, 1095, 473–482.PubMedGoogle Scholar
  56. Ko, W. G., Kang, T. H., Lee, S. J., Kim, Y. C., & Lee, B. H. (2002). Effects of luteolin on the inhibition of proliferation and induction of apoptosis in human myeloid leukaemia cells. Phytotherapy Research, 3, 295–298.Google Scholar
  57. Kong, L., Tanito, M., Huang, Z., Li, F., et al. (2007). Delay of photoreceptor degeneration in tubby mouse by sulforaphane. Journal of Neurochemistry, 101, 1041–1052.PubMedGoogle Scholar
  58. Kraft, A. D., Johnson, D. A., & Johnson, J. A. (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. Journal of Neuroscience, 24, 1101–1112.PubMedGoogle Scholar
  59. Lee-Hilz, Y. Y., Boerboom, A. M., Westphal, A. H., et al. (2006). Pro-oxidant activity of flavonoids induces EpRE-mediated gene expression. Chemical Research in Toxicology, 19, 1499–1505.PubMedGoogle Scholar
  60. Liu, R. H. (2004). Potential synergy of phytochemicals in cancer prevention: Mechanism of action. Journal of Nutrition, 134, 3479S–3485S.PubMedGoogle Scholar
  61. Liu, Y. C., Hsieh, C. W., Wu, C. C., & Wung, B. S. (2007). Chalcone inhibits the activation of NF-kappaB and STAT3 in endothelial cells via endogenous electrophile. Life Sciences, 80, 1420–1430.PubMedGoogle Scholar
  62. Madan, B., Batra, S., & Ghosh, B. (2000). 2’-Hydroxychalcone inhibits nuclear factor-kappaB and blocks tumor necrosis factor-alpha- and lipopolysaccharide-induced adhesion of neutrophils to human umbilical vein endothelial cells. Molecular Pharmacology, 58, 526–534.PubMedGoogle Scholar
  63. Mandel, S. A., Avramovich-Tirosh, Y., Reznichenko, L., Zheng, H., et al. (2005). Multifunctional activities of green tea catechins in neuroprotection. Modulation of cell survival genes, iron-dependent oxidative stress and PKC signaling pathway. Neurosignals, 14, 46–60.PubMedGoogle Scholar
  64. Mattson, M. P. (2008). Hormesis defined. Ageing Research Reviews, 7, 1–7.PubMedGoogle Scholar
  65. Mattson, M. P., & Cheng, A. (2006). Neurohormetic phytochemicals: Low-dose toxins that induce adaptive neuronal stress responses. Trends in Neurosciences, 29, 632–639.PubMedGoogle Scholar
  66. Mattson, M. P., Goodman, Y., Luo, H., Fu, W., & Furukawa, K. (1997). Activation of NF-kappaB protects hippocampal neurons against oxidative stress-induced apoptosis: Evidence for induction of manganese superoxide dismutase and suppression of peroxynitrite production and protein tyrosine nitration. Journal of Neuroscience Research, 49, 681–697.PubMedGoogle Scholar
  67. Mattson, M. P., & Meffert, M. K. (2006). Roles for NF-kappaB in nerve cell survival, plasticity, and disease. Cell Death and Differentiation, 13, 852–860.PubMedGoogle Scholar
  68. McGuire, S. O., Sortwell, C. E., Shukitt-Hale, B., Joseph, J. A., et al. (2006). Dietary supplementation with blueberry extract improves survival of transplanted dopamine neurons. Nutritional Neuroscience, 9, 251–258.PubMedGoogle Scholar
  69. McWalter, G. K., Higgins, L. G., McLellan, L. I., Henderson, C. J., et al. (2004). Transcription factor Nrf2 is essential for induction of NAD(P)H:quinine oxidoreductase 1, glutathione S-transferases, and glutamate cysteine ligase by broccoli seeds and isothiocyanates. Journal of Nutrition, 134, 3499S–3506S.PubMedGoogle Scholar
  70. Milne, J. C., Lambert, P. D., Schenk, S., Carney, D. P., et al. (2007). Small molecule activators of SIRT1 as therapeutics for the treatment of type 2 diabetes. Nature, 450, 712–716.PubMedGoogle Scholar
  71. Miura, Y., Chiba, T., Tomita, I., et al. (2001). Tea catechins prevent the development of atherosclerosis in apoprotein E-deficient mice. Journal of Nutrition, 131, 27–32.PubMedGoogle Scholar
  72. Morse, M. A., Eklind, K. I., Amin, S. G., Hecht, S. S., & Chung, F. L. (1989a). Effects of alkyl chain length on the inhibition of NNK-induced lung neoplasia in A/J mice by arylalkyl isothiocyanates. Carcinogenesis, 10, 1757–1759.PubMedGoogle Scholar
  73. Morse, M. A., Wang, C. X., Stoner, G. D., Mandal, S., et al. (1989b). Inhibition of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced DNA adduct formation and tumorigenicity in the lung of F344 rats by dietary phenethyl isothiocyanate. Cancer Research, 49, 549–553.PubMedGoogle Scholar
  74. Morse, M. A., Zu, H., Galati, A. J., Schmidt, C. J., & Stoner, G. D. (1993). Dose-related inhibition by dietary phenethyl isothiocyanate of esophageal tumorigenesis and DNA methylation induced by N-nitrosomethylbenzylamine in rats. Cancer Letters, 72, 103–110.PubMedGoogle Scholar
  75. Murakami, A., Nakamura, Y., Koshimizu, K., et al. (2002). FA15, a hydrophobic derivative of ferulic acid, suppresses inflammatory responses and skin tumor promotion: Comparison with ferulic acid. Cancer Letters, 180, 121–129.PubMedGoogle Scholar
  76. Nair, S., Li, W., & Kong, A. N. (2007). Natural dietary anti-cancer chemopreventive compounds: Redox-mediated differential signaling mechanisms in cytoprotection of normal cells versus cytotoxicity in tumor cells. Acta Pharmacologica Sinica, 28, 59–72.Google Scholar
  77. Nair, S., Xu, C., Shen, G., Hebbar, V., et al. (2006). Pharmacogenomics of phenolic antioxidant butylated hydroxyanisole (BHA) in the small intestine and liver of Nrf2 knockout and C57BL/6 J mice. Pharmaceutical Research, 11, 2621–2637.Google Scholar
  78. Nishikawa, A., Furukawa, F., Uneyama, C., Ikezaki, S., et al. (1996). Chemopreventive effects of phenethyl isothiocyanate on lung and pancreatic tumorigenesis in N-nitrosobis(2-oxopropyl)amine-treated hamsters. Carcinogenesis, 17, 1381–1384.PubMedGoogle Scholar
  79. Nishimura, R., Tabata, K., Arakawa, M., et al. (2007). Isobavachalcone, a chalcone constituent of Angelica keiskei, induces apoptosis in neuroblastoma. Biological and Pharmaceutical Bulletin, 30, 1878–1883.PubMedGoogle Scholar
  80. Ohori, H., Yamakoshi, H., Tomizawa, M., Shibuya, M., et al. (2006). Synthesis and biological analysis of new curcumin analogues bearing an enhanced potential for the medicinal treatment of cancer. Molecular Cancer Therapeutics, 5, 2563–2571.PubMedGoogle Scholar
  81. Okawara, M., Katsuki, H., Kurimoto, E., Shibata, H., Kume, T., & Akaike, A. (2007). Resveratrol protects dopaminergic neurons in midbrain slice culture from multiple insults. Biochemical Pharmacology, 73, 550–560.PubMedGoogle Scholar
  82. Ou, L., Kong, L. Y., Zhang, X. M., & Niwa, M. (2003). Oxidation of ferulic acid by momordic charantia peroxidase and related anti-inflammation activity changes. Biological and Pharmaceutical Bulletin, 26, 1511–1516.PubMedGoogle Scholar
  83. Pae, H. O., Jeong, G. S., Jeong, S. O., et al. (2007). Roles of heme oxygenase-1 in curcumin-induced growth inhibition in rat smooth muscle cells. Experimental & Molecular Medicine, 39, 267–277.Google Scholar
  84. Park, A. M., & Dong, Z. (2003). Signal transduction pathways: Targets for green and black tea polyphenols. Journal of Biochemistry and Molecular Biology, 36, 66–77.PubMedGoogle Scholar
  85. Parker, J. A., Arango, M., Abderrahmane, S., Lambert, E., Tourette, C., Catoire, H., et al. (2005). Resveratrol rescues mutant polyglutamine cytotoxicity in nematode and mammalian neurons. Nature Genetics, 37, 349–350.PubMedGoogle Scholar
  86. Radak, Z., Chung, H. Y., Koltai, E., Taylor, A. W., & Goto, S. (2008). Exercise, oxidative stress and hormesis. Ageing Research Reviews, 7, 34–42.PubMedGoogle Scholar
  87. Robb, E. L., Page, M. M., Wiens, B. E., & Stuart, J. A. (2008). Molecular mechanisms of oxidative stress resistance induced by resveratrol: Specific and progressive induction of MnSOD. Biochemical and Biophysical Research Communications, 367, 406–412.PubMedGoogle Scholar
  88. Rushworth, S. A., Ogborne, R. M., Charalambos, C. A., & O’Connell, M. A. (2006). Role of protein kinase C delta in curcumin-induced antioxidant response element-mediated gene expression in human monocytes. Biochemical and Biophysical Research Communications, 341, 1007–1016.PubMedGoogle Scholar
  89. Scapagnini, G., Colombrita, C., Amadio, M., D’Agata, V., et al. (2006). Curcumin activates defensive genes and protects neurons against oxidative stress. Antioxidants & Redox Signaling, 8, 395–403.Google Scholar
  90. Schwarting, A. E. (1963). Poisonous seeds and fruits. Progress in Chemical Toxicology, 18, 385–401.Google Scholar
  91. Shen, G., Xu, C., Hu, R., Jain, M. R., et al. (2005). Comparison of (-)-epigallocatechin–3-gallate elicited liver and small intestine gene expression profiles between C57BL/6 J mice and C57BL/6 J/Nrf2 (-/-) mice. Pharmaceutical Research, 11, 1805–1820.Google Scholar
  92. Shen, G., Xu, C., Hu, R., Jain, M. R., et al. (2006). Modulation of nuclear factor E2-related factor 2-mediated gene expression in mice liver and small intestine by cancer chemopreventive agent curcumin. Molecular Cancer Therapeutics, 1, 39–51.Google Scholar
  93. Shi, R. X., Ong, C. N., & Shen, H. M. (2004). Luteolin sensitizes tumor necrosis factor-alpha-induced apoptosis in human tumor cells. Oncogene, 23, 7712–7721.PubMedGoogle Scholar
  94. Son, H. Y., Nishikawa, A., Furukawa, F., Lee, I. S., et al. (2000). Modifying effects of 4-phenylbutyl isothiocyanate on N-nitrosobis(2-oxopropyl)amine-induced tumorigenesis in hamsters. Cancer Letters, 160, 141–147.PubMedGoogle Scholar
  95. Sones, K., Heaney, R. K., & Fenwick, G. R. (1984). An estimate of the mean daily intake of glucosinolates from cruciferous vegetables in the UK. Journal of the Science of Food and Agriculture, 35, 712–720.Google Scholar
  96. Srinivasan, M., Sudheer, A. R., & Menon, V. P. (2007). Ferulic acid: Therapeutic potential through its antioxidant property. Journal of Clinical Biochemistry and Nutrition, 40, 92–100.PubMedGoogle Scholar
  97. Stoner, G. D., Adams, C., Kresty, L. A., Amin, S. G., et al. (1998). Inhibition of N’-nitrosonornicotine-induced esophageal tumorigenesis by 3-phenylpropyl isothiocyanate. Carcinogenesis, 12, 2139–2143.Google Scholar
  98. Sudakin, D. L. (2003). Biopesticides. Toxicological Reviews, 22, 83–90.PubMedGoogle Scholar
  99. Sultana, R., Ravagna, A., Mohmmad-Abdul, H., et al. (2005). Ferulic acid ethyl ester protect neurons against amyloid beta-peptide (1–42)-induced oxidative stress and neurotoxicity: Relationship to antioxidant activity. Journal of Neurochemistry, 92, 749–758.PubMedGoogle Scholar
  100. Tedeschi, E., Suzuki, H., & Menegazzi, M. (2002). Antiinflammatory action of EGCG, the main component of green tea, through STAT-1 inhibition. Annals of the New York Academy of Sciences, 973, 435–437.PubMedGoogle Scholar
  101. Tetsuka, T., Baier, L. D., & Morrison, A. R. (1996). Antioxidants inhibit interleukin-1 induced cyclooxygenase and nitric oxide synthase expression in rat mesanglial cells. Evidence for post-transcriptional regulation. Journal of Biological Chemistry, 271, 1168–1169.Google Scholar
  102. Tookey, H. L., VanEtten, C. H., & Daxenbichler, M. E. (1980). Glucosinolates. In I. E. Liener (Ed.), Toxic constituents of plant stuffs (pp. 103–142). New York, NY: Academic Press.Google Scholar
  103. Trinh, K., Moore, K., Wes, P. D., Muchowski, P. J., Dey, J., Andrews, L., et al. (2008). Induction of the phase II detoxification pathway suppresses neuron loss in Drosophila models of Parkinson’s disease. Journal of Neuroscience, 28, 465–472.PubMedGoogle Scholar
  104. Tuteja, N., Singh, M. B., Misra, M. K., Bhalla, P. L., & Tuteja, R. (2001). Molecular mechanisms of DNA damage and repair: Progress in plants. Critical Reviews in Biochemistry and Molecular Biology, 36, 337–397.PubMedGoogle Scholar
  105. Ueda, H., Yamazaki, C., & Yamazaki, M. (2003). Inhibitory effect of Perilla leaf extract and luteolin on mouse skin tumor promotion. Biological and Pharmaceutical Bulletin, 4, 560–563.Google Scholar
  106. van der Horst, A., & Burgering, B. M. (2007). Stressing the role of FoxO proteins in lifespan and disease. Nature Reviews. Molecular Cell Biology, 8, 440–450.PubMedGoogle Scholar
  107. Wang, Q., Sun, A. Y., Simonyi, A., Jensen, M. D., et al. (2005). Neuroprotective mechanisms of curcumin against cerebral ischemia-induced neuronal apoptosis and behavioral deficits. Journal of Neuroscience Research, 82, 138–148.PubMedGoogle Scholar
  108. Wang, C., Zhang, D., Li, G., Liu, J., Tian, J., Fu, F., et al. (2007). Neuroprotective effects of on brain ischemic injury. Experimental Brain Research, 177, 533–539.Google Scholar
  109. Wattenberg, L. W. (1977). Inhibition of carcinogenic effects of polycyclic hydrocarbons by benzyl isothiocyanate and related compounds. Journal of the National Cancer Institute, 58, 395–398.PubMedGoogle Scholar
  110. Wattenberg, L. W. (1992). Inhibition of carcinogenesis by minor dietary constituents. Cancer Research, 52, 2085S–2091S.PubMedGoogle Scholar
  111. Wattenberg, L. W., Coccia, J. B., & Galbraith, A. R. (1994). Inhibition of carcinogen-induced pulmonary and mammary carcinogenesis by chalcone administered subsequent to carcinogen exposure. Cancer Letters, 83, 165–169.PubMedGoogle Scholar
  112. Wilson, M. A., Shukitt-Hale, B., Kalt, W., Ingram, D. K., Joseph, J. A., & Wolkow, C. A. (2006). Blueberry polyphenols increase lifespan and thermotolerance in Caenorhabditis elegans. Aging Cell, 5, 59–68.PubMedGoogle Scholar
  113. Wruck, C. J., Claussen, M., Fuhrmann, G., Römer, L., et al. (2007). Luteolin protects rat PC12 and C6 cells against MPP+ induced toxicity via an ERK dependent Keap1-Nrf2-ARE pathway. Journal of Neural Transmission. Supplementum, 72, 57–67.PubMedGoogle Scholar
  114. Wu, C. C., Hsu, M. C., Hsieh, C. W., et al. (2006). Upregulation of heme oxygenase-1 by epigallocatechin-3-gallate via the phosphatidylinositol 3-kinase/Akt and ERK pathways. Life Sciences, 78, 2889–2897.PubMedGoogle Scholar
  115. Xu, Y., Ku, B., Cui, L., Li, X., Barish, P. A., Foster, T. C., et al. (2007). Curcumin reverses impaired hippocampal neurogenesis and increases serotonin receptor 1A mRNA and brain-derived neurotrophic factor expression in chronically stressed rats. Brain Research, 1162, 9–18.PubMedGoogle Scholar
  116. Xu, C., Yuan, X., Pan, Z., Shen, G., et al. (2006). Mechanism of action of isothiocyanates: The induction of ARE-regulated genes is associated with activation of ERK and JNK and the phosphorylation and nuclear translocation of Nrf2. Molecular Cancer Therapeutics, 8, 1918–1926.Google Scholar
  117. Ye, C. L., Liu, J. W., & Wei, D. Z. (2004). In vitro anti-tumor activity of 2’, 4’-dihydroxy-6’-methoxy-3’, 5’-dimethylchalcone against six established human cancer cell lines. Pharmacological Research, 50, 505–510.PubMedGoogle Scholar
  118. Ye, C. L., Liu, J. W., & Wei, D. Z. (2005). In vivo antitumor activity by 2’, 4’-dihydroxy-6’-methoxy-3’, 5’-dimethylchalcone in a solid human carcinoma xenograft model. Cancer Chemotherapy and Pharmacology, 55, 447–452.PubMedGoogle Scholar
  119. Yu, R., Lei, W., Mandlekar, S., Weber, M. J., Der, C. J., Wu, J., et al. (1999a). Role of mitogen-activated protein kinase pathway in the induction of phase II detoxifying enzymes by chemical. Journal of Biological Chemistry, 274, 27545–27552.PubMedGoogle Scholar
  120. Yu, Z., Zhou, D., Bruce-Keller, A. J., Kindy, M. S., & Mattson, M. P. (1999b). Lack of the p50 subunit of nuclear factor-kappaB increases the vulnerability of hippocampal neurons to excitotoxic injury. Journal of Neuroscience, 19, 8856–8865.PubMedGoogle Scholar
  121. Zbarsky, V., Datla, K. P., Parkar, S., Rai, D. K., Aruoma, O. I., & Dexter, D. T. (2005). Neuroprotective properties of the natural phenolic antioxidants curcumin and naringenin but not quercetin and fisetin in a 6-OHDA model of Parkinson’s disease. Free Radical Research, 39, 1119–1125.PubMedGoogle Scholar
  122. Zhang, B., Safa, R., Rusciano, D., & Osborne, N. N. (2007). Epigallocatechin gallate, an active ingredient from green tea, attenuates damaging influences to the retina caused by ischemia/reperfusion. Brain Research, 1159, 40–53.PubMedGoogle Scholar

Copyright information

© Humana Press 2008

Authors and Affiliations

  • Tae Gen Son
    • 1
  • Simonetta Camandola
    • 1
    Email author
  • Mark P. Mattson
    • 1
  1. 1.Laboratory of NeurosciencesNational Institute on Aging, Intramural Research ProgramBaltimoreUSA

Personalised recommendations