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Role of Nitric Oxide Synthases in Parkinson’s Disease: A Review on the Antioxidant and Anti-inflammatory Activity of Polyphenols

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Abstract

Natural polyphenols can exert protective action on a number of pathological conditions including neurodegenerative disorders. The neuroprotective effects of many polyphenols rely on their ability to permeate brain barrier and here directly scavenge pathological concentration of reactive oxygen and nitrogen species and chelate transition metal ions. Importantly, polyphenols modulate neuroinflammation by inhibiting the expression of inflammatory genes and the level of intracellular antioxidants. Parkinson’s disease (PD) is a neurodegenerative disorder characterized by several abnormalities including inflammation, mitochondrial dysfunction, iron accumulation and oxidative stress. There is considerable evidence showing that cellular oxidative damage occurring in PD might result also from the actions of altered production of nitric oxide (NO). Indeed, high levels of neuronal and inducible NO synthase (NOS) were found in substantia nigra of patients and animal models of PD. Here, we evaluate the involvement of NOS/NO in PD and explore the neuroprotective activity of natural polyphenol compounds in terms of anti-inflammatory and antioxidant action.

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References

  1. Clifford MN (2004) Diet-derived phenols in plasma and tissues and their implications for health. Planta Med 70:1103–1114

    Article  PubMed  CAS  Google Scholar 

  2. Beecher GR (2003) Overview of dietary flavonoids: nomenclature, occurrence and intake. J Nutr 133:3248S–3254S

    PubMed  CAS  Google Scholar 

  3. Middleton E Jr, Kandaswami C, Theoharides TC (2000) The effects of plant flavonoids on mammalian cells: implications for inflammation, heart disease, and cancer. Pharmacol Rev 52:673–751

    PubMed  CAS  Google Scholar 

  4. Rotondo S, de Gaetano G (2000) Protection from cardiovascular disease by wine and its derived products. Epidemiological evidence and biological mechanisms. World Rev Nutr Diet 87:90–113

    Article  PubMed  CAS  Google Scholar 

  5. Ramassamy C (2006) Emerging role of polyphenolic compounds in the treatment of neurodegenerative diseases: a review of their intracellular targets. Eur J Pharmacol 545:51–64

    Article  PubMed  CAS  Google Scholar 

  6. Schaffer S, Eckert GP, Schmitt-Schillig S, Muller WE (2006) Plant foods and brain aging: a critical appraisal. Forum Nutr 59:86–115

    Article  PubMed  CAS  Google Scholar 

  7. Wee LM, Long LH, Whiteman M, Halliwell B (2003) Factors affecting the ascorbate- and phenolic-dependent generation of hydrogen peroxide in Dulbecco’s Modified Eagles Medium. Free Radic Res 37:1123–1130

    Article  PubMed  CAS  Google Scholar 

  8. de la Lastra CA, Villegas I (2007) Resveratrol as an antioxidant and pro-oxidant agent: mechanisms and clinical implications. Biochem Soc Trans 35:1156–1160

    Article  PubMed  Google Scholar 

  9. Lee KW, Lee HJ (2006) The roles of polyphenols in cancer chemoprevention. Biofactors 26:105–121

    PubMed  CAS  Google Scholar 

  10. Frei B, Higdon JV (2003) Antioxidant activity of tea polyphenols in vivo: evidence from animal studies. J Nutr 133:3275S–3284S

    PubMed  CAS  Google Scholar 

  11. Heim KE, Tagliaferro AR, Bobilya DJ (2002) Flavonoid antioxidants: chemistry, metabolism and structure–activity relationships. J Nutr Biochem 13:572–584

    Article  PubMed  CAS  Google Scholar 

  12. Nakagawa T, Yokozawa T (2002) Direct scavenging of nitric oxide and superoxide by green tea. Food Chem Toxicol 40:1745–1750

    Article  PubMed  CAS  Google Scholar 

  13. Mattson MP, Magnus T (2006) Ageing and neuronal vulnerability. Nat Rev Neurosci 7:278–294

    Article  PubMed  CAS  Google Scholar 

  14. Mosley RL, Benner EJ, Kadiu I et al (2006) Neuroinflammation, oxidative stress and the pathogenesis of Parkinson’s disease. Clin Neurosci Res 6:261–281

    Article  PubMed  CAS  Google Scholar 

  15. Manach C, Scalbert A, Morand C et al (2004) Polyphenols: food sources and bioavailability. Am J Clin Nutr 79:727–747

    PubMed  CAS  Google Scholar 

  16. Mandel S, Amit T, Reznichenko L et al (2006) Green tea catechins as brain-permeable, natural iron chelators-antioxidants for the treatment of neurodegenerative disorders. Mol Nutr Food Res 50:229–234

    Article  PubMed  CAS  Google Scholar 

  17. Youdim KA, Shukitt-Hale B, Joseph JA (2004) Flavonoids and the brain: interactions at the blood-brain barrier and their physiological effects on the central nervous system. Free Radic Biol Med 37:1683–1693

    Article  PubMed  CAS  Google Scholar 

  18. Mokni M, Elkahoui S, Limam F et al (2007) Effect of resveratrol on antioxidant enzyme activities in the brain of healthy rat. Neurochem Res 32:981–987

    Article  PubMed  CAS  Google Scholar 

  19. Mandel S, Weinreb O, Amit T, Youdim MB (2004) Cell signaling pathways in the neuroprotective actions of the green tea polyphenol (­)-epigallocatechin-3-gallate: implications for neurodegenerative diseases. J Neurochem 88:1555–1569

    PubMed  CAS  Google Scholar 

  20. Masella R, Di Benedetto R, Vari R et al (2005) Novel mechanisms of natural antioxidant compounds in biological systems: involvement of glutathione and glutathione-related enzymes. J Nutr Biochem 16:577–586

    Article  PubMed  CAS  Google Scholar 

  21. Kim HP, Son KH, Chang HW, Kang SS (2004) Anti-inflammatory plant flavonoids and cellular action mechanisms. J Pharmacol Sci 96:229–245

    Article  PubMed  CAS  Google Scholar 

  22. Lorenz P, Roychowdhury S, Engelmann M et al (2003) Oxyresveratrol and resveratrol are potent antioxidants and free radical scavengers: effect on nitrosative and oxidative stress derived from microglial cells. Nitric Oxide 9:64–76

    Article  PubMed  CAS  Google Scholar 

  23. Lau FC, Shukitt-Hale B, Joseph JA (2005) The beneficial effects of fruit polyphenols on brain aging. Neurobiol Aging 26(Suppl 1):128–132

    Article  PubMed  CAS  Google Scholar 

  24. Esposito E, Rotilio D, Di Matteo V et al (2002) A review of specific dietary antioxidants and the effects on biochemical mechanisms related to neurodegenerative processes. Neurobiol Aging 23:719–735

    Article  PubMed  CAS  Google Scholar 

  25. Olanow CW, Tatton WG (1999) Etiology and pathogenesis of Parkinson’s disease. Annu Rev Neurosci 22:123–144

    Article  PubMed  CAS  Google Scholar 

  26. Kidd PM (2000) Parkinson’s disease as multifactorial oxidative neurodegeneration: implications for integrative management. Altern Med Rev 5:502–529

    PubMed  CAS  Google Scholar 

  27. Jenner P (2003) Oxidative stress in Parkinson’s disease. Ann Neurol 53(Suppl 3):S26–S36 discussion S36–S28

    Article  PubMed  CAS  Google Scholar 

  28. Whitton PS (2007) Inflammation as a causative factor in the aetiology of Parkinson’s disease. Br J Pharmacol 150:963–976

    Article  PubMed  CAS  Google Scholar 

  29. Betarbet R, Sherer TB, MacKenzie G et al (2000) Chronic systemic pesticide exposure reproduces features of Parkinson’s disease. Nat Neurosci 3:1301–1306

    Article  PubMed  CAS  Google Scholar 

  30. Thiruchelvam M, Brockel BJ, Richfield EK et al (2000) Potentiated and preferential effects of combined paraquat and maneb on nigrostriatal dopamine systems: environmental risk factors for Parkinson’s disease? Brain Res 873:225–234

    Article  PubMed  CAS  Google Scholar 

  31. Thiruchelvam M, Richfield EK, Baggs RB et al (2000) The nigrostriatal dopaminergic system as a preferential target of repeated exposures to combined paraquat and maneb: implications for Parkinson’s disease. J Neurosci 20:9207–9214

    PubMed  CAS  Google Scholar 

  32. Lee MK, Kang SJ, Poncz M et al (2007) Resveratrol protects SH-SY5Y neuroblastoma cells from apoptosis induced by dopamine. Exp Mol Med 39:376–384

    PubMed  CAS  Google Scholar 

  33. Dore S (2005) Unique properties of polyphenol stilbenes in the brain: more than direct antioxidant actions; gene/protein regulatory activity. Neurosignals 14:61–70

    Article  PubMed  CAS  Google Scholar 

  34. Guo S, Bezard E, Zhao B (2005) Protective effect of green tea polyphenols on the SH-SY5Y cells against 6-OHDA induced apoptosis through ROS-NO pathway. Free Radic Biol Med 39:682–695

    Article  PubMed  CAS  Google Scholar 

  35. Weinreb O, Mandel S, Amit T, Youdim MB (2004) Neurological mechanisms of green tea polyphenols in Alzheimer’s and Parkinson’s diseases. J Nutr Biochem 15:506–516

    Article  PubMed  CAS  Google Scholar 

  36. Schapira AH (2006) Etiology of Parkinson’s disease. Neurology 66:S10–S23

    PubMed  Google Scholar 

  37. Schapira AH (2007) Mitochondrial dysfunction in Parkinson’s disease. Cell Death Differ 14:1261–1266

    Article  PubMed  CAS  Google Scholar 

  38. Schapira AH (2008) Mitochondria in the aetiology and pathogenesis of Parkinson’s disease. Lancet Neurol 7:97–109

    Article  PubMed  CAS  Google Scholar 

  39. Shukla R, Rajani M, Srivastava N et al (2006) Nitrite and malondialdehyde content in cerebrospinal fluid of patients with Parkinson’s disease. Int J Neurosci 116:1391–1402

    Article  PubMed  CAS  Google Scholar 

  40. Molina JA, Jimenez-Jimenez FJ, Navarro JA et al (1996) Cerebrospinal fluid nitrate levels in patients with Parkinson’s disease. Acta Neurol Scand 93:123–126

    Article  PubMed  CAS  Google Scholar 

  41. Zhang L, Dawson VL, Dawson TM (2006) Role of nitric oxide in Parkinson’s disease. Pharmacol Ther 109:33–41

    Article  PubMed  CAS  Google Scholar 

  42. Kavya R, Saluja R, Singh S, Dikshit M (2006) Nitric oxide synthase regulation and diversity: implications in Parkinson’s disease. Nitric Oxide 15:280–294

    Article  PubMed  CAS  Google Scholar 

  43. Alderton WK, Cooper CE, Knowles RG (2001) Nitric oxide synthases: structure, function and inhibition. Biochem J 357:593–615

    Article  PubMed  CAS  Google Scholar 

  44. Estevez AG, Spear N, Thompson JA et al (1998) Nitric oxide-dependent production of cGMP supports the survival of rat embryonic motor neurons cultured with brain-derived neurotrophic factor. J Neurosci 18:3708–3714

    PubMed  CAS  Google Scholar 

  45. Saha RN, Pahan K (2006) Regulation of inducible nitric oxide synthase gene in glial cells. Antioxid Redox Signal 8:929–947

    Article  PubMed  CAS  Google Scholar 

  46. Lacza Z, Pankotai E, Csordas A et al (2006) Mitochondrial NO and reactive nitrogen species production: does mtNOS exist? Nitric Oxide 14:162–168

    Article  PubMed  CAS  Google Scholar 

  47. Carreras MC, Franco MC, Peralta JG, Poderoso JJ (2004) Nitric oxide, complex I, and the modulation of mitochondrial reactive species in biology and disease. Mol Aspects Med 25:125–139

    Article  PubMed  CAS  Google Scholar 

  48. Giulivi C, Kato K, Cooper CE (2006) Nitric oxide regulation of mitochondrial oxygen consumption I: cellular physiology. Am J Physiol Cell Physiol 291:C1225–C1231

    Article  PubMed  CAS  Google Scholar 

  49. Hunot S, Boissiere F, Faucheux B et al (1996) Nitric oxide synthase and neuronal vulnerability in Parkinson’s disease. Neuroscience 72:355–363

    Article  PubMed  CAS  Google Scholar 

  50. Eve DJ, Nisbet AP, Kingsbury AE et al (1998) Basal ganglia neuronal nitric oxide synthase mRNA expression in Parkinson’s disease. Brain Res Mol Brain Res 63:62–71

    Article  PubMed  CAS  Google Scholar 

  51. Muramatsu Y, Kurosaki R, Watanabe H et al (2003) Cerebral alterations in a MPTP-mouse model of Parkinson’s disease—an immunocytochemical study. J Neural Transm 110:1129–1144

    Article  PubMed  CAS  Google Scholar 

  52. Chalimoniuk M, Langfort J, Lukacova N, Marsala J (2004) Upregulation of guanylyl cyclase expression and activity in striatum of MPTP-induced parkinsonism in mice. Biochem Biophys Res Commun 324:118–126

    Article  PubMed  CAS  Google Scholar 

  53. Cutillas B, Espejo M, Gil J et al (1999) Caspase inhibition protects nigral neurons against 6-OHDA-induced retrograde degeneration. Neuroreport 10:2605–2608

    Article  PubMed  CAS  Google Scholar 

  54. Schulz JB, Matthews RT, Muqit MM et al (1995) Inhibition of neuronal nitric oxide synthase by 7-nitroindazole protects against MPTP-induced neurotoxicity in mice. J Neurochem 64:936–939

    Article  PubMed  CAS  Google Scholar 

  55. Hantraye P, Brouillet E, Ferrante R et al (1996) Inhibition of neuronal nitric oxide synthase prevents MPTP-induced parkinsonism in baboons. Nat Med 2:1017–1021

    Article  PubMed  CAS  Google Scholar 

  56. Beal MF (1998) Excitotoxicity and nitric oxide in Parkinson’s disease pathogenesis. Ann Neurol 44:S110–S114

    Article  PubMed  CAS  Google Scholar 

  57. Kim PK, Zamora R, Petrosko P, Billiar TR (2001) The regulatory role of nitric oxide in apoptosis. Int Immunopharmacol 1:1421–1441

    Article  PubMed  CAS  Google Scholar 

  58. Mandir AS, Przedborski S, Jackson-Lewis V et al (1999) Poly(ADP-ribose) polymerase activation mediates 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism. Proc Natl Acad Sci USA 96:5774–5779

    Article  PubMed  CAS  Google Scholar 

  59. Pennathur S, Jackson-Lewis V, Przedborski S, Heinecke JW (1999) Mass spectrometric quantification of 3-nitrotyrosine, ortho-tyrosine, and o,o′-dityrosine in brain tissue of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated mice, a model of oxidative stress in Parkinson’s disease. J Biol Chem 274:34621–34628

    Article  PubMed  CAS  Google Scholar 

  60. Ferrante RJ, Hantraye P, Brouillet E, Beal MF (1999) Increased nitrotyrosine immunoreactivity in substantia nigra neurons in MPTP treated baboons is blocked by inhibition of neuronal nitric oxide synthase. Brain Res 823:177–182

    Article  PubMed  CAS  Google Scholar 

  61. Good PF, Hsu A, Werner P et al (1998) Protein nitration in Parkinson’s disease. J Neuropathol Exp Neurol 57:338–342

    Article  PubMed  CAS  Google Scholar 

  62. Giasson BI, Murray IV, Trojanowski JQ, Lee VM (2001) A hydrophobic stretch of 12 amino acid residues in the middle of alpha-synuclein is essential for filament assembly. J Biol Chem 276:2380–2386

    Article  PubMed  CAS  Google Scholar 

  63. Beyer K (2007) Mechanistic aspects of Parkinson’s disease: alpha-synuclein and the biomembrane. Cell Biochem Biophys 47:285–299

    Article  PubMed  CAS  Google Scholar 

  64. Hess DT, Matsumoto A, Nudelman R, Stamler JS (2001) S-nitrosylation: spectrum and specificity. Nat Cell Biol 3:E46–E49

    Article  PubMed  CAS  Google Scholar 

  65. Hess DT, Matsumoto A, Kim SO et al (2005) Protein S-nitrosylation: purview and parameters. Nat Rev Mol Cell Biol 6:150–166

    Article  PubMed  CAS  Google Scholar 

  66. Uehara T, Nakamura T, Yao D et al (2006) S-nitrosylated protein-disulphide isomerase links protein misfolding to neurodegeneration. Nature 441:513–517

    Article  PubMed  CAS  Google Scholar 

  67. Lipton SA, Gu Z, Nakamura T (2007) Inflammatory mediators leading to protein misfolding and uncompetitive/fast off-rate drug therapy for neurodegenerative disorders. Int Rev Neurobiol 82:1–27

    Article  PubMed  CAS  Google Scholar 

  68. Chung KK, Dawson VL, Dawson TM (2005) S-nitrosylation in Parkinson’s disease and related neurodegenerative disorders. Methods Enzymol 396:139–150

    Article  PubMed  CAS  Google Scholar 

  69. Chung KK, Thomas B, Li X et al (2004) S-nitrosylation of parkin regulates ubiquitination and compromises parkin’s protective function. Science 304:1328–1331

    Article  PubMed  CAS  Google Scholar 

  70. Brunori M, Forte E, Arese M et al (2006) Nitric oxide and the respiratory enzyme. Biochim Biophys Acta 1757:1144–1154

    Article  PubMed  CAS  Google Scholar 

  71. Moncada S (2000) Nitric oxide and cell respiration: physiology and pathology. Verh K Acad Geneeskd Belg 62:171–179 discussion 179–181

    PubMed  CAS  Google Scholar 

  72. Lopez-Figueroa MO, Caamano C, Morano MI et al (2000) Direct evidence of nitric oxide presence within mitochondria. Biochem Biophys Res Commun 272:129–133

    Article  PubMed  CAS  Google Scholar 

  73. Kanai A, Epperly M, Pearce L et al (2004) Differing roles of mitochondrial nitric oxide synthase in cardiomyocytes and urothelial cells. Am J Physiol Heart Circ Physiol 286:H13–H21

    Article  PubMed  CAS  Google Scholar 

  74. Giulivi C (2007) Mitochondria as generators and targets of nitric oxide. Novartis Found Symp 287:92–100 discussion 100–104

    Article  PubMed  CAS  Google Scholar 

  75. Gao HM, Hong JS, Zhang W, Liu B (2002) Distinct role for microglia in rotenone-induced degeneration of dopaminergic neurons. J Neurosci 22:782–790

    PubMed  CAS  Google Scholar 

  76. He Y, Appel S, Le W (2001) Minocycline inhibits microglial activation and protects nigral cells after 6-hydroxydopamine injection into mouse striatum. Brain Res 909:187–193

    Article  PubMed  CAS  Google Scholar 

  77. Gao HM, Liu B, Zhang W, Hong JS (2003) Critical role of microglial NADPH oxidase-derived free radicals in the in vitro MPTP model of Parkinson’s disease. Faseb J 17:1954–1956

    PubMed  CAS  Google Scholar 

  78. Wilms H, Zecca L, Rosenstiel P et al (2007) Inflammation in Parkinson’s diseases and other neurodegenerative diseases: cause and therapeutic implications. Curr Pharm Des 13:1925–1928

    Article  PubMed  CAS  Google Scholar 

  79. Knott C, Stern G, Wilkin GP (2000) Inflammatory regulators in Parkinson’s disease: iNOS, lipocortin-1, and cyclooxygenases-1 and -2. Mol Cell Neurosci 16:724–739

    Article  PubMed  CAS  Google Scholar 

  80. Mancuso C, Scapagini G, Curro D et al (2007) Mitochondrial dysfunction, free radical generation and cellular stress response in neurodegenerative disorders. Front Biosci 12:1107–1123

    Article  PubMed  CAS  Google Scholar 

  81. Liberatore GT, Jackson-Lewis V, Vukosavic S et al (1999) Inducible nitric oxide synthase stimulates dopaminergic neurodegeneration in the MPTP model of Parkinson disease. Nat Med 5:1403–1409

    Article  PubMed  CAS  Google Scholar 

  82. Chen J, Wersinger C, Sidhu A (2003) Chronic stimulation of D1 dopamine receptors in human SK-N-MC neuroblastoma cells induces nitric-oxide synthase activation and cytotoxicity. J Biol Chem 278:28089–28100

    Article  PubMed  CAS  Google Scholar 

  83. Reif DW, Simmons RD (1990) Nitric oxide mediates iron release from ferritin. Arch Biochem Biophys 283:537–541

    Article  PubMed  CAS  Google Scholar 

  84. Schulz JB, Beal MF (1995) Neuroprotective effects of free radical scavengers and energy repletion in animal models of neurodegenerative disease. Ann N Y Acad Sci 765:100–110 discussion 116–108

    Article  PubMed  CAS  Google Scholar 

  85. Nanjo F, Honda M, Okushio K et al (1993) Effects of dietary tea catechins on alpha-tocopherol levels, lipid peroxidation, and erythrocyte deformability in rats fed on high palm oil and perilla oil diets. Biol Pharm Bull 16:1156–1159

    PubMed  CAS  Google Scholar 

  86. Guo Q, Zhao B, Shen S et al (1999) ESR study on the structure-antioxidant activity relationship of tea catechins and their epimers. Biochim Biophys Acta 1427:13–23

    PubMed  CAS  Google Scholar 

  87. Haenen GR, Paquay JB, Korthouwer RE, Bast A (1997) Peroxynitrite scavenging by flavonoids. Biochem Biophys Res Commun 236:591–593

    Article  PubMed  CAS  Google Scholar 

  88. Heijnen CG, Haenen GR, van Acker FA et al (2001) Flavonoids as peroxynitrite scavengers: the role of the hydroxyl groups. Toxicol In Vitro 15:3–6

    Article  PubMed  CAS  Google Scholar 

  89. Paquay JB, Haenen GR, Stender G et al (2000) Protection against nitric oxide toxicity by tea. J Agric Food Chem 48:5768–5772

    Article  PubMed  CAS  Google Scholar 

  90. Mercer LD, Kelly BL, Horne MK, Beart PM (2005) Dietary polyphenols protect dopamine neurons from oxidative insults and apoptosis: investigations in primary rat mesencephalic cultures. Biochem Pharmacol 69:339–345

    Article  PubMed  CAS  Google Scholar 

  91. Lopez-Lopez G, Moreno L, Cogolludo A et al (2004) Nitric oxide (NO) scavenging and NO protecting effects of quercetin and their biological significance in vascular smooth muscle. Mol Pharmacol 65:851–859

    Article  PubMed  CAS  Google Scholar 

  92. Yokozawa T, Rhyu DY, Cho EJ (2004) (­)-Epicatechin 3-O-gallate ameliorates the damages related to peroxynitrite production by mechanisms distinct from those of other free radical inhibitors. J Pharm Pharmacol 56:231–239

    Article  PubMed  CAS  Google Scholar 

  93. Mandel S, Youdim MB (2004) Catechin polyphenols: neurodegeneration and neuroprotection in neurodegenerative diseases. Free Radic Biol Med 37:304–317

    Article  PubMed  CAS  Google Scholar 

  94. Lu KT, Chiou RY, Chen LG et al (2006) Neuroprotective effects of resveratrol on cerebral ischemia-induced neuron loss mediated by free radical scavenging and cerebral blood flow elevation. J Agric Food Chem 54:3126–3131

    Article  PubMed  CAS  Google Scholar 

  95. Sonmez U, Sonmez A, Erbil G et al (2007) Neuroprotective effects of resveratrol against traumatic brain injury in immature rats. Neurosci Lett 420:133–137

    Article  PubMed  CAS  Google Scholar 

  96. Bastianetto S, Zheng WH, Quirion R (2000) Neuroprotective abilities of resveratrol and other red wine constituents against nitric oxide-related toxicity in cultured hippocampal neurons. Br J Pharmacol 131:711–720

    Article  PubMed  CAS  Google Scholar 

  97. Virgili M, Contestabile A (2000) Partial neuroprotection of in vivo excitotoxic brain damage by chronic administration of the red wine antioxidant agent, trans-resveratrol in rats. Neurosci Lett 281:123–126

    Article  PubMed  CAS  Google Scholar 

  98. Gong QH, Wang Q, Shi JS et al (2007) Inhibition of caspases and intracellular free Ca2+ concentrations are involved in resveratrol protection against apoptosis in rat primary neuron cultures. Acta Pharmacol Sin 28:1724–1730

    Article  PubMed  CAS  Google Scholar 

  99. Rotilio G, Aquilano K, Ciriolo MR (2003) Interplay of Cu, Zn superoxide dismutase and nitric oxide synthase in neurodegenerative processes. IUBMB Life 55:629–634

    Article  PubMed  CAS  Google Scholar 

  100. Amazzal L, Lapotre A, Quignon F, Bagrel D (2007) Mangiferin protects against 1-methyl-4-phenylpyridinium toxicity mediated by oxidative stress in N2A cells. Neurosci Lett 418:159–164

    Article  PubMed  CAS  Google Scholar 

  101. Martinez G, Giuliani A, Leon OS et al (2001) Effect of Mangifera indica L. extract (QF808) on protein and hepatic microsome peroxidation. Phytother Res 15:581–585

    Article  PubMed  CAS  Google Scholar 

  102. Andreu GP, Delgado R, Velho JA et al (2005) Iron complexing activity of mangiferin, a naturally occurring glucosylxanthone, inhibits mitochondrial lipid peroxidation induced by Fe2+-citrate. Eur J Pharmacol 513:47–55

    Article  PubMed  CAS  Google Scholar 

  103. Liu KL, Chen HW, Wang RY et al (2006) DATS reduces LPS-induced iNOS expression, NO production, oxidative stress, and NF-kappaB activation in RAW 264.7 macrophages. J Agric Food Chem 54:3472–3478

    Article  PubMed  CAS  Google Scholar 

  104. Geng Y, Zhang B, Lotz M (1993) Protein tyrosine kinase activation is required for lipopolysaccharide induction of cytokines in human blood monocytes. J Immunol 151:6692–6700

    PubMed  CAS  Google Scholar 

  105. Kempuraj D, Madhappan B, Christodoulou S et al (2005) Flavonols inhibit proinflammatory mediator release, intracellular calcium ion levels and protein kinase C theta phosphorylation in human mast cells. Br J Pharmacol 145:934–944

    Article  PubMed  CAS  Google Scholar 

  106. Wadsworth TL, McDonald TL, Koop DR (2001) Effects of Ginkgo biloba extract (EGb 761) and quercetin on lipopolysaccharide-induced signaling pathways involved in the release of tumor necrosis factor-alpha. Biochem Pharmacol 62:963–974

    Article  PubMed  CAS  Google Scholar 

  107. Baumann J, Wurm G, von Bruchhausen F (1980) Prostaglandin synthetase inhibition by flavonoids and phenolic compounds in relation to their O2-scavenging properties (author’s transl). Arch Pharm (Weinheim) 313:330–337

    Article  CAS  Google Scholar 

  108. Liang YC, Huang YT, Tsai SH et al (1999) Suppression of inducible cyclooxygenase and inducible nitric oxide synthase by apigenin and related flavonoids in mouse macrophages. Carcinogenesis 20:1945–1952

    Article  PubMed  CAS  Google Scholar 

  109. Pang JL, Ricupero DA, Huang S et al (2006) Differential activity of kaempferol and quercetin in attenuating tumor necrosis factor receptor family signaling in bone cells. Biochem Pharmacol 71:818–826

    Article  PubMed  CAS  Google Scholar 

  110. Cheon BS, Kim YH, Son KS et al (2000) Effects of prenylated flavonoids and biflavonoids on lipopolysaccharide-induced nitric oxide production from the mouse macrophage cell line RAW 264.7. Planta Med 66:596–600

    Article  PubMed  CAS  Google Scholar 

  111. Chen Y, Yang L, Lee TJ (2000) Oroxylin A inhibition of lipopolysaccharide-induced iNOS and COX-2 gene expression via suppression of nuclear factor-kappaB activation. Biochem Pharmacol 59:1445–1457

    Article  PubMed  CAS  Google Scholar 

  112. Youdim KA, Joseph JA (2001) A possible emerging role of phytochemicals in improving age-related neurological dysfunctions: a multiplicity of effects. Free Radic Biol Med 30:583–594

    Article  PubMed  CAS  Google Scholar 

  113. Abd El Mohsen MM, Kuhnle G, Rechner AR et al (2002) Uptake and metabolism of epicatechin and its access to the brain after oral ingestion. Free Radic Biol Med 33:1693–1702

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

This work was partially supported by Ministero della Salute, MIUR and FIRB “Idee Progettuali”. We thank Dr. Giovanni Auricchio for his advice in the matter of PD inflammatory processes and helpful critical reading of the manuscript.

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Correspondence to Maria Rosa Ciriolo.

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Special issue article in honor of Dr. Anna Maria Giuffrida-Stella.

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Aquilano, K., Baldelli, S., Rotilio, G. et al. Role of Nitric Oxide Synthases in Parkinson’s Disease: A Review on the Antioxidant and Anti-inflammatory Activity of Polyphenols. Neurochem Res 33, 2416–2426 (2008). https://doi.org/10.1007/s11064-008-9697-6

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