Curcumin: A potential neuroprotective agent in Parkinson's disease

Current Pharmaceutical Design

Volumn 18, Issue 1, 2012, Pages 91-99

  Mythri, R B ^a   Srinivas Bharath, M M ^a  

^a NATIONAL INSTITUTE OF MENTAL HEALTH AND NEUROSCIENCES   (India)

Author keywords

Curcumin; Molecular mechanisms; Neuroprotection; Parkinson's disease; Polyphenols; Therapeutics

Indexed keywords

1,6 HEPTADIENE 3,5 DIONE 1,7 BIS(4 HYDROXY 3 METHOXYPHENYL); ANTIOXIDANT; CURCUMIN; CYCLOCURCUMIN; DEMETHOXYCURCUMIN; DIDEMETHOXYCURCUMIN; DOPAMINE; DRUG METABOLITE; NANOPARTICLE; PHOSPHATIDYLCHOLINE; PIPERINE; TURMERIC; UNCLASSIFIED DRUG;

ANTIOXIDANT ACTIVITY; CLINICAL TRIAL (TOPIC); CORPUS STRIATUM; CURCUMA LONGA; DIET SUPPLEMENTATION; DOPAMINERGIC NERVE CELL; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG BRAIN LEVEL; DRUG DELIVERY SYSTEM; DRUG LIVER LEVEL; DRUG METABOLISM; DRUG SOLUBILITY; DRUG STABILITY; DRUG TRANSFORMATION; ENZYME INHIBITION; HUMAN; MOLECULARLY TARGETED THERAPY; NEUROPROTECTION; NONHUMAN; OXIDATIVE STRESS; PARKINSON DISEASE; PRIORITY JOURNAL; REVIEW; SUBSTANTIA NIGRA;

AGE FACTORS; ANIMALS; ANTIPARKINSON AGENTS; CORPUS STRIATUM; CURCUMA; CURCUMIN; DISEASE MODELS, ANIMAL; DOPAMINE; HUMANS; NEURONS; NEUROPROTECTIVE AGENTS; PARKINSON DISEASE;

EID: 84855858783     PISSN: 13816128     EISSN: 18734286     Source Type: Journal    
DOI: 10.2174/138161212798918995     Document Type: Review

References (144)

1. Jankovic J. Parkinson's disease: clinical features and diagnosis. J Neurol Neurosurg Psychiatry 2008; 79: 368-76.
2. Miyasaki JM, Martin W, Suchowersky O, Weiner WJ, Lang AE. Practice parameter: initiation of treatment for Parkinson's disease: an evidence-based review: report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2002; 58: 11-7.
3. Olanow CW, Watts RL, Koller WC. An algorithm (decision tree) for the management of Parkinson's disease (2001): treatment guidelines. Neurology 2001; 56: S1-88.
4. Bharath MM. Therapeutic strategies in Parkinson's Disease. Recent patents on Endocrine, Metabolic & Immune Drug Discovery 2008; 2: 135-47.
5. Kumar V. Potential medicinal plants for CNS disorders: an overview. Phytother Res 2006; 20: 1023-35.
6. Sparreboom A, Cox MC, Acharya MR, Figg WD. Herbal remedies in the United States: potential adverse interactions with anticancer agents. J Clin Oncol 2004; 22: 2489-503.
7. Tsao R. Chemistry and biochemistry of dietary polyphenols. Nutrients 2010; 2: 1231-46.
8. Joe B, Vijaykumar M, Lokesh BR. Biological properties of curcumin-cellular and molecular mechanisms of action. Crit Rev Food Sci Nutr 2004; 44: 97-111.
9. Ganguli M, Chandra V, Kamboh MI, et al. Apolipoprotein E polymorphism and Alzheimer disease: The Indo-US Cross-National Dementia Study. Arch Neurol 2000; 57: 824-30.
10. Muthane U, Yasha TC, Shankar SK. Low numbers and no loss of melanized nigral neurons with increasing age in normal human brains from India. Ann Neurol 1998; 43: 283-7.
11. Alladi PA, Mahadevan A, Yasha TC, Raju TR, Shankar SK, Muthane U. Absence of age-related changes in nigral dopaminergic neurons of Asian Indians: relevance to lower incidence of Parkinson's disease. Neuroscience 2009; 159: 236-45.
12. Sinha R, Anderson DE, McDonald SS, Greenwald P. Cancer risk and diet in India. J Postgrad Med 2003; 49: 222-8.
13. Srinivasan K. Plant foods in the management of diabetes mellitus: spices as beneficial antidiabetic food adjuncts. Int J Food Sci Nutr 2005; 56: 399-414.
14. Mythri RB, Harish G, Dubey SK, Misra K, Bharath MM. Glutamoyl diester of the dietary polyphenol curcumin offers improved protection against peroxynitrite-mediated nitrosative stress and damage of brain mitochondria in vitro: implications for Parkinson's disease. Mol Cell Biochem 2011; 347: 135-43.
15. Kurien BT, Scofield RH. Increasing the solubility of the nutraceutical curcumin by heat and inhibition of oxidative modification. Mol Nutr Food Res 2009; 53: 308.
16. Goel A, Kunnumakkara AB, Aggarwal BB. Curcumin as "Curecumin": from kitchen to clinic. Biochem Pharmacol 2008; 75: 787-809.
17. Ravindran PN. Turmeric-the golden spice of life. Turmeric: The genus Curcuma: Taylor and Francis Group; 2006. 1-14.
18. Barclay LR, Vinqvist MR, Mukai K, et al. On the antioxidant mechanism of curcumin: classical methods are needed to determine antioxidant mechanism and activity. Org Lett 2000; 2: 2841-3.
19. Priyadarsini KI, Maity DK, Naik GH, et al. Role of phenolic O-H and methylene hydrogen on the free radical reactions and antioxidant activity of curcumin. Free Radic Biol Med 2003; 35: 475-84.
20. Iwunze MO, McEwan D. Peroxynitrite interaction with curcumin solubilized in ethanolic solution. Cell Mol Biol (Noisy-le-grand) 2004; 50: 749-52.
21. Mythri RB, Jagatha B, Pradhan N, Andersen J, Bharath MM. Mitochondrial complex I inhibition in Parkinson's disease: how can curcumin protect mitochondria? Antioxid Redox Signal 2007; 9: 399-408.
22. Mishra B, Priyadarsini KI, Bhide MK, Kadam RM, Mohan H. Reactions of superoxide radicals with curcumin: probable mechanisms by optical spectroscopy and EPR. Free Radic Res 2004; 38: 355-62.
23. Toniolo R, Di Narda F, Susmel S, Martelli M, Martelli L, Bontempelli G. Quenching of superoxide ions by curcumin. A mechanistic study in acetonitrile. Ann Chim 2002; 92: 281-8.
24. Ohara K, Mizukami W, Tokunaga A, Nagaoka S, Uno H, Mukai. Kinetic Study of the Mechanism of Free-Radical Scavenging Action in Curcumin: Effects of Solvent and pH. Bull Chem Soc Jpn 2005; 78: 615-21.
25. Adams BK, Cai J, Armstrong J, et al. EF24, a novel synthetic curcumin analog, induces apoptosis in cancer cells via a redoxdependent mechanism. Anticancer Drugs 2005; 16: 263-75.
26. Khopde SM, Priyadarsini KI, Guha SN, Satav JG, Venkatesan P, Rao MN. Inhibition of radiation-induced lipid peroxidation by tetrahydrocurcumin: possible mechanisms by pulse radiolysis. Biosci Biotechnol Biochem 2000; 64: 503-9.
27. Motterlini R, Foresti R, Bassi R, Green CJ. Curcumin, an antioxidant and anti-inflammatory agent, induces heme oxygenase-1 and protects endothelial cells against oxidative stress. Free Radic Biol Med 2000; 28: 1303-12.
28. Pan MH, Huang TM, Lin JK. Biotransformation of curcumin through reduction and glucuronidation in mice. Drug Metab Dispos 1999; 27: 486-94.
29. Ravindranath V, Chandrasekhara N. Absorption and tissue distribution of curcumin in rats. Toxicology 1980; 16: 259-65.
30. Suresh D, Srinivasan K. Tissue distribution & elimination of capsaicin, piperine & curcumin following oral intake in rats. Indian J Med Res 2010; 131: 682-91.
31. Garcea G, Jones DJ, Singh R, et al. Detection of curcumin and its metabolites in hepatic tissue and portal blood of patients following oral administration. Br J Cancer 2004; 90: 1011-5.
32. Wang Q, Sun AY, Simonyi A, et al. Neuroprotective mechanisms of curcumin against cerebral ischemia-induced neuronal apoptosis and behavioral deficits. J Neurosci Res 2005; 82: 138-48.
33. Begum AN, Jones MR, Lim GP, et al. Curcumin structurefunction, bioavailability, and efficacy in models of neuroinflammation and Alzheimer's disease. J Pharmacol Exp Ther 2008; 326: 196-208.
34. Bishnoi M, Chopra K, Rongzhu L, Kulkarni SK. Protective effect of curcumin and its combination with piperine (bioavailability enhancer) against haloperidol-associated neurotoxicity: cellular and neurochemical evidence. Neurotox Res 2011; 20: 215-25.
35. Shoba G, Joy D, Joseph T, Majeed M, Rajendran R, Srinivas PS. Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers. Planta Med 1998; 64: 353-6.
36. Ray B, Bisht S, Maitra A, Lahiri DK. Neuroprotective and neurorescue effects of a novel polymeric nanoparticle formulation of curcumin (NanoCurc) in the neuronal cell culture and animal model: implications for Alzheimer's disease. J Alzheimers Dis 2011; 23: 61-77.
37. Gupta V, Aseh A, Rios CN, Aggarwal BB, Mathur AB. Fabrication and characterization of silk fibroin-derived curcumin nanoparticles for cancer therapy. Int J Nanomedicine 2009; 4: 115-22.
38. Gupta NK, Dixit VK. Bioavailability enhancement of curcumin by complexation with phosphatidyl choline. J Pharm Sci 2011; 100: 1987-95.
39. Gupta NK, Dixit VK. Development and evaluation of vesicular system for curcumin delivery. Arch Dermatol Res 2011; 303: 89-101.
40. Cao FL, Xi YW, Tang L, Yu AH, Zhai GX. [Preparation and characterization of curcumin loaded gelatin microspheres for lung targeting]. Zhong Yao Cai 2009; 32: 423-6.
41. Kumar V, Lewis SA, Mutalik S, Shenoy DB, Venkatesh, Udupa N. Biodegradable microspheres of curcumin for treatment of inflammation. Indian J Physiol Pharmacol 2002; 46: 209-17.
42. Bansal SS, Vadhanam MV, Gupta RC. Development and in vitro-in vivo evaluation of polymeric implants for continuous systemic delivery of curcumin. Pharm Res 2011; 28: 1121-30.
43. Song Z, Feng R, Sun M, et al. Curcumin-loaded PLGA-PEGPLGA triblock copolymeric micelles: Preparation, pharmacokinetics and distribution in vivo. J Colloid Interface Sci 2011; 354: 116-23.
44. Kurien BT, Scofield RH. Curcumin/turmeric solubilized in sodium hydroxide inhibits HNE protein modification--an in vitro study. J Ethnopharmacol 2007; 110: 368-73.
45. Kurien BT, Jackson K, Scofield RH. Immunoblotting of multiple antigenic peptides. Electrophoresis 1998; 19: 1659-61.
46. Kurien BT, Scofield RH. Oral administration of heat-solubilized curcumin for potentially increasing curcumin bioavailability in experimental animals. Int J Cancer 2009; 125: 1992-3.
47. Takeuchi T, Ishidoh T, Iijima H, et al. Structural relationship of curcumin derivatives binding to the BRCT domain of human DNA polymerase lambda. Genes Cells 2006; 11: 223-35.
48. Leu TH, Su SL, Chuang YC, Maa MC. Direct inhibitory effect of curcumin on Src and focal adhesion kinase activity. Biochem Pharmacol 2003; 66: 2323-31.
49. Fang J, Lu J, Holmgren A. Thioredoxin reductase is irreversibly modified by curcumin: a novel molecular mechanism for its anticancer activity. J Biol Chem 2005; 280: 25284-90.
50. Reddy S, Aggarwal BB. Curcumin is a non-competitive and selective inhibitor of phosphorylase kinase. FEBS Lett 1994; 341: 19-22.
51. Skrzypczak-Jankun E, Zhou K, McCabe NP, Selman SH, Jankun J. Structure of curcumin in complex with lipoxygenase and its significance in cancer. Int J Mol Med 2003; 12: 17-24.
52. Gupta KK, Bharne SS, Rathinasamy K, Naik NR, Panda D. Dietary antioxidant curcumin inhibits microtubule assembly through tubulin binding. FEBS J 2006; 273: 5320-32.
53. Baum L, Ng A. Curcumin interaction with copper and iron suggests one possible mechanism of action in Alzheimer's disease animal models. J Alzheimers Dis 2004; 6: 367-77; discussion 443-9.
54. Ishihara M, Sakagami H. Re-evaluation of cytotoxicity and iron chelation activity of three beta-diketones by semiempirical molecular orbital method. In Vivo 2005; 19: 119-23.
55. Wortelboer HM, Usta M, van der Velde AE, et al. Interplay between MRP inhibition and metabolism of MRP inhibitors: the case of curcumin. Chem Res Toxicol 2003; 16: 1642-51.
56. Bilmen JG, Khan SZ, Javed MH, Michelangeli F. Inhibition of the SERCA Ca2+ pumps by curcumin. Curcumin putatively stabilizes the interaction between the nucleotide-binding and phosphorylation domains in the absence of ATP. Eur J Biochem 2001; 268: 6318-27.
57. Logan-Smith MJ, Lockyer PJ, East JM, Lee AG. Curcumin, a molecule that inhibits the Ca2+-ATPase of sarcoplasmic reticulum but increases the rate of accumulation of Ca2+. J Biol Chem 2001; 276: 46905-11.
58. Yang F, Lim GP, Begum AN, Ubeda OJ, et al. Curcumin inhibits formation of amyloid beta oligomers and fibrils, binds plaques, and reduces amyloid in vivo. J Biol Chem 2005; 280: 5892-901.
59. Began G, Sudharshan E, Appu Rao AG. Inhibition of lipoxygenase 1 by phosphatidylcholine micelles-bound curcumin. Lipids 1998; 33: 1223-8.
60. Jeyapaul J, Jaiswal AK. Nrf2 and c-Jun regulation of antioxidant response element (ARE)-mediated expression and induction of gamma-glutamylcysteine synthetase heavy subunit gene. Biochem Pharmacol 2000; 59: 1433-9.
61. Wild AC, Moinova HR, Mulcahy RT. Regulation of gammaglutamylcysteine synthetase subunit gene expression by the transcription factor Nrf2. J Biol Chem 1999; 274: 33627-336.
62. Chanas SA, Jiang Q, McMahon M, et al. Loss of the Nrf2 transcription factor causes a marked reduction in constitutive and inducible expression of the glutathione S-transferase Gsta1, Gsta2, Gstm1, Gstm2, Gstm3 and Gstm4 genes in the livers of male and female mice. Biochem J 2002; 365: 405-16.
63. Ye SF, Hou ZQ, Zhong LM, Zhang QQ. Effect of curcumin on the induction of glutathione S-transferases and NADP(H):quinone oxidoreductase and its possible mechanism of action. Yao Xue Xue Bao 2007; 42: 376-80.
64. McNally SJ, Harrison EM, Ross JA, Garden OJ, Wigmore SJ. Curcumin induces heme oxygenase 1 through generation of reactive oxygen species, p38 activation and phosphatase inhibition. Int J Mol Med 2007; 19: 165-72.
65. Jobin C, Bradham CA, Russo MP, Juma B, Narula AS, Brenner DA, et al. Curcumin blocks cytokine-mediated NF-kappa B activation and proinflammatory gene expression by inhibiting inhibitory factor I-kappa B kinase activity. J Immunol 1999; 163: 3474-83.
66. Plummer SM, Holloway KA, Manson MM, et al. Inhibition of cyclo-oxygenase 2 expression in colon cells by the chemopreventive agent curcumin involves inhibition of NF-kappaB activation via the NIK/IKK signalling complex. Oncogene 1999; 18: 6013-20.
67. Shishodia S, Sethi G, Aggarwal BB. Curcumin: getting back to the roots. Ann N Y Acad Sci 2005; 1056: 206-17.
68. Bharti AC, Donato N, Aggarwal BB. Curcumin (diferuloylmethane) inhibits constitutive and IL-6-inducible STAT3 phosphorylation in human multiple myeloma cells. J Immunol 2003; 171: 3863-71.
69. Chen A, Xu J. Activation of PPAR{gamma} by curcumin inhibits Moser cell growth and mediates suppression of gene expression of cyclin D1 and EGFR. Am J Physiol Gastrointest Liver Physiol 2005; 288: G447-56.
70. Bierhaus A, Zhang Y, Quehenberger P, et al. The dietary pigment curcumin reduces endothelial tissue factor gene expression by inhibiting binding of AP-1 to the DNA and activation of NF-kappa B. Thromb Haemost 1997; 77: 772-82.
71. Huang TS, Lee SC, Lin JK. Suppression of c-Jun/AP-1 activation by an inhibitor of tumor promotion in mouse fibroblast cells. Proc Natl Acad Sci U S A 1991; 88: 5292-6.
72. Xu YX, Pindolia KR, Janakiraman N, Chapman RA, Gautam SC. Curcumin inhibits IL1 alpha and TNF-alpha induction of AP-1 and NF-kB DNA-binding activity in bone marrow stromal cells. Hematopathol Mol Hematol 1997; 11: 49-62.
73. Rahman I, Marwick J, Kirkham P. Redox modulation of chromatin remodeling: impact on histone acetylation and deacetylation, NFkappaB and pro-inflammatory gene expression. Biochem Pharmacol 2004; 68: 1255-67.
74. Yu S, Zheng W, Xin N, et al. Curcumin prevents dopaminergic neuronal death through inhibition of the c-Jun N-terminal kinase pathway. Rejuvenation Res 2010; 13: 55-64.
75. Chen YR, Tan TH. Inhibition of the c-Jun N-terminal kinase (JNK) signaling pathway by curcumin. Oncogene 1998; 17: 173-8.
76. Aggarwal BB, Bhatt ID, Ichikawa H, et al. Curcumin-biological and medicinal properties. Turmeric: the genus Curcuma. London: Taylor and Francis Group; 2006. 297-368.
77. Shishodia S, Singh T, Chaturvedi MM. Modulation of transcription factors by curcumin. Adv Exp Med Biol 2007; 595: 127-48.
78. Chen J, Tang XQ, Zhi JL, et al. Curcumin protects PC12 cells against 1-methyl-4-phenylpyridinium ion-induced apoptosis by bcl-2-mitochondria-ROS-iNOS pathway. Apoptosis 2006; 11: 943-53.
79. Dale WM, Russell C. A study of the irradiation of catalase by ionizing radiations in the presence of cysteine, cystine and glutathione. Biochem J 1956; 62: 50-7.
80. Lavoie S, Chen Y, Dalton TP, et al. Curcumin, quercetin, and tBHQ modulate glutathione levels in astrocytes and neurons: importance of the glutamate cysteine ligase modifier subunit. J Neurochem 2009; 108: 1410-22.
81. Jagatha B, Mythri RB, Vali S, Bharath MM. Curcumin treatment alleviates the effects of glutathione depletion in vitro and in vivo: therapeutic implications for Parkinson's disease explained via in silico studies. Free Radic Biol Med 2008; 44: 907-17.
82. Stridh MH, Correa F, Nodin C, et al. Enhanced glutathione efflux from astrocytes in culture by low extracellular Ca(2+) and curcumin. Neurochem Res 2010; 35: 1231-8.
83. Jiao Y, Wilkinson Jt, Christine Pietsch E, et al. Iron chelation in the biological activity of curcumin. Free Radic Biol Med 2006; 40: 1152-60.
84. Jiao Y, Wilkinson Jt, Di X, et al. Curcumin, a cancer chemopreventive and chemotherapeutic agent, is a biologically active iron chelator. Blood 2009; 113: 462-9.
85. Ali RE, Rattan SI. Curcumin's biphasic hormetic response on proteasome activity and heat-shock protein synthesis in human keratinocytes. Ann N Y Acad Sci 2006; 1067: 394-9.
86. Sharma S, Kulkarni SK, Agrewala JN, Chopra K. Curcumin attenuates thermal hyperalgesia in a diabetic mouse model of neuropathic pain. Eur J Pharmacol 2006; 536: 256-61.
87. Sharma S, Kulkarni SK, Chopra K. Curcumin, the active principle of turmeric (Curcuma longa), ameliorates diabetic nephropathy in rats. Clin Exp Pharmacol Physiol 2006; 33: 940-5.
88. Duvoix A, Blasius R, Delhalle S, et al. Chemopreventive and therapeutic effects of curcumin. Cancer Lett 2005; 223: 181-90.
89. Cheng TC, Lin CS, Hsu CC, Chen LJ, Cheng KC, Cheng JT. Activation of muscarinic M-1 cholinoceptors by curcumin to increase glucose uptake into skeletal muscle isolated from Wistar rats. Neurosci Lett 2009; 465: 238-41.
90. Peeyush KT, Gireesh G, Jobin M, Paulose CS. Neuroprotective role of curcumin in the cerebellum of streptozotocin-induced diabetic rats. Life Sci 2009; 85: 704-10.
91. Alwi I, Santoso T, Suyono S, et al. The effect of curcumin on lipid level in patients with acute coronary syndrome. Acta Med Indones 2008; 40: 201-10.
92. Ejaz A, Wu D, Kwan P, Meydani M. Curcumin inhibits adipogenesis in 3T3-L1 adipocytes and angiogenesis and obesity in C57/BL mice. J Nutr 2009; 139: 919-25.
93. Jang EM, Choi MS, Jung UJ, et al. Beneficial effects of curcumin on hyperlipidemia and insulin resistance in high-fat-fed hamsters. Metabolism 2008; 57: 1576-83.
94. Dikshit M, Rastogi L, Shukla R, Srimal RC. Prevention of ischaemia-induced biochemical changes by curcumin & quinidine in the cat heart. Indian J Med Res 1995; 101: 31-5.
95. Thaloor D, Miller KJ, Gephart J, Mitchell PO, Pavlath GK. Systemic administration of the NF-kappaB inhibitor curcumin stimulates muscle regeneration after traumatic injury. Am J Physiol 1999; 277: C320-9.
96. Lao CD, Ruffin MTt, Normolle D, et al. Dose escalation of a curcuminoid formulation. BMC Complement Altern Med 2006; 6: 10.
97. Qureshi S, Shah AH, Ageel AM. Toxicity studies on Alpinia galanga and Curcuma longa. Planta Med 1992; 58: 124-7.
98. Shankar TN, Shantha NV, Ramesh HP, Murthy IA, Murthy VS. Toxicity studies on turmeric (Curcuma longa): acute toxicity studies in rats, guineapigs & monkeys. Indian J Exp Biol 1980; 18: 73-5.
99. Kim SJ, Son TG, Park HR, et al. Curcumin stimulates proliferation of embryonic neural progenitor cells and neurogenesis in the adult hippocampus. J Biol Chem 2008; 283: 14497-505.
100. Xu Y, Ku B, Cui L, Li X, Barish PA, Foster TC, et al. Curcumin reverses impaired hippocampal neurogenesis and increases serotonin receptor 1A mRNA and brain-derived neurotrophic factor expression in chronically stressed rats. Brain Res 2007; 1162: 9-18.
101. Scapagnini G, Colombrita C, Amadio M, D'Agata V, Arcelli E, Sapienza M, et al. Curcumin activates defensive genes and protects neurons against oxidative stress. Antioxid Redox Signal 2006; 8: 395-403.
102. Lim GP, Chu T, Yang F, Beech W, Frautschy SA, Cole GM. The curry spice curcumin reduces oxidative damage and amyloid pathology in an Alzheimer transgenic mouse. J Neurosci 2001; 21: 8370-7.
103. Thiyagarajan M, Sharma SS. Neuroprotective effect of curcumin in middle cerebral artery occlusion induced focal cerebral ischemia in rats. Life Sci 2004; 74: 969-85.
104. Lin MS, Hung KS, Chiu WT, et al. Curcumin enhances neuronal survival in N-methyl-d-aspartic acid toxicity by inducing RANTES expression in astrocytes via PI-3K and MAPK signaling pathways. Prog Neuropsychopharmacol Biol Psychiatry 2011; 35: 931-8.
105. Wu A, Ying Z, Gomez-Pinilla F. Dietary curcumin counteracts the outcome of traumatic brain injury on oxidative stress, synaptic plasticity, and cognition. Exp Neurol 2006; 197: 309-17.
106. Xu Y, Ku BS, Yao HY, et al. The effects of curcumin on depressive-like behaviors in mice. Eur J Pharmacol 2005; 518: 40-6.
107. Al-Omar FA, Nagi MN, Abdulgadir MM, Al Joni KS, Al-Majed AA. Immediate and delayed treatments with curcumin prevents forebrain ischemia-induced neuronal damage and oxidative insult in the rat hippocampus. Neurochem Res 2006; 31: 611-8.
108. Mehla J, Reeta KH, Gupta P, Gupta YK. Protective effect of curcumin against seizures and cognitive impairment in a pentylenetetrazole-kindled epileptic rat model. Life Sci 2010; 87: 596-603.
109. Kumar A, Naidu PS, Seghal N, Padi SS. Effect of curcumin on intracerebroventricular colchicine-induced cognitive impairment and oxidative stress in rats. J Med Food 2007; 10: 486-94.
110. Zbarsky V, Datla KP, Parkar S, Rai DK, Aruoma OI, Dexter DT. 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 Radic Res 2005; 39: 1119-25.
111. Arai T, Fukae J, Hatano T, et al. Up-regulation of hMUTYH, a DNA repair enzyme, in the mitochondria of substantia nigra in Parkinson's disease. Acta Neuropathol 2006; 112: 139-45.
112. Rao KS. DNA repair in aging rat neurons. Neuroscience 2007; 145: 1330-40.
113. Yasuhara T, Hara K, Sethi KD, Morgan JC, Borlongan CV. Increased 8-OHdG levels in the urine, serum, and substantia nigra of hemiparkinsonian rats. Brain Res 2007; 1133: 49-52.
114. Grin IR, Konorovsky PG, Nevinsky GA, Zharkov DO. Heavy metal ions affect the activity of DNA glycosylases of the fpg family. Biochemistry (Mosc) 2009; 74: 1253-9.
115. Hegde ML, Hegde PM, Holthauzen LM, Hazra TK, Rao KS, Mitra S. Specific Inhibition of NEIL-initiated repair of oxidized base damage in human genome by copper and iron: potential etiological linkage to neurodegenerative diseases. J Biol Chem 2010; 285: 28812-25.
116. Yoritaka A, Hattori N, Uchida K, Tanaka M, Stadtman ER, Mizuno Y. Immunohistochemical detection of 4-hydroxynonenal protein adducts in Parkinson disease. Proc Natl Acad Sci U S A 1996; 93: 2696-701.
117. Raza H, John A. 4-hydroxynonenal induces mitochondrial oxidative stress, apoptosis and expression of glutathione Stransferase A4-4 and cytochrome P450 2E1 in PC12 cells. Toxicol Appl Pharmacol 2006; 216: 309-18.
118. Zhu YG, Chen XC, Chen ZZ, et al. Curcumin protects mitochondria from oxidative damage and attenuates apoptosis in cortical neurons. Acta Pharmacol Sin 2004; 25: 1606-12.
119. Raza H, John A, Brown EM, Benedict S, Kambal A. Alterations in mitochondrial respiratory functions, redox metabolism and apoptosis by oxidant 4-hydroxynonenal and antioxidants curcumin and melatonin in PC12 cells. Toxicol Appl Pharmacol 2008; 226: 161-8.
120. Rajeswari A. Curcumin protects mouse brain from oxidative stress caused by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Eur Rev Med Pharmacol Sci 2006; 10: 157-61.
121. Dickinson DA, Iles KE, Zhang H, Blank V, Forman HJ. Curcumin alters EpRE and AP-1 binding complexes and elevates glutamatecysteine ligase gene expression. FASEB J 2003; 17: 473-5.
122. LaVoie MJ, Ostaszewski BL, Weihofen A, Schlossmacher MG, Selkoe DJ. Dopamine covalently modifies and functionally inactivates parkin. Nat Med 2005; 11: 1214-21.
123. Bharath S, Hsu M, Kaur D, Rajagopalan S, Andersen JK. Glutathione, iron and Parkinson's disease. Biochem Pharmacol 2002; 64: 1037-48.
124. Wang J, Du XX, Jiang H, Xie JX. Curcumin attenuates 6-hydroxydopamine-induced cytotoxicity by anti-oxidation and nuclear factor-kappa B modulation in MES23.5 cells. Biochem Pharmacol 2009; 78: 178-83.
125. Rajeswari A, Sabesan M. Inhibition of monoamine oxidase-B by the polyphenolic compound, curcumin and its metabolite tetrahydrocurcumin, in a model of Parkinson's disease induced by MPTP neurodegeneration in mice. Inflammopharmacology 2008; 16: 96-9.
126. Wang SL, Li Y, Wen Y, et al. Curcumin, a potential inhibitor of up-regulation of TNF-alpha and IL-6 induced by palmitate in 3T3-L1 adipocytes through NF-kappaB and JNK pathway. Biomed Environ Sci 2009; 22: 32-9.
127. Luo Y, Hattori A, Munoz J, Qin ZH, Roth GS. Intrastriatal dopamine injection induces apoptosis through oxidation-involved activation of transcription factors AP-1 and NF-kappaB in rats. Mol Pharmacol 1999; 56: 254-64.
128. Sawada H, Ibi M, Kihara T, et al. Estradiol protects dopaminergic neurons in a MPP+Parkinson's disease model. Neuropharmacology 2002; 42: 1056-64.
129. Brouet I, Ohshima H. Curcumin, an anti-tumour promoter and antiinflammatory agent, inhibits induction of nitric oxide synthase in activated macrophages. Biochem Biophys Res Commun 1995; 206: 533-40.
130. Chan MM, Huang HI, Fenton MR, Fong D. In vivo inhibition of nitric oxide synthase gene expression by curcumin, a cancer preventive natural product with anti-inflammatory properties. Biochem Pharmacol 1998; 55: 1955-62.
131. Pan MH, Lin-Shiau SY, Lin JK. Comparative studies on the suppression of nitric oxide synthase by curcumin and its hydrogenated metabolites through down-regulation of IkappaB kinase and NFkappaB activation in macrophages. Biochem Pharmacol 2000; 60: 1665-76.
132. Pandey N, Strider J, Nolan WC, Yan SX, Galvin JE. Curcumin inhibits aggregation of alpha-synuclein. Acta Neuropathol 2008; 115: 479-89.
133. Wang MS, Boddapati S, Emadi S, Sierks MR. Curcumin reduces alpha-synuclein induced cytotoxicity in Parkinson's disease cell model. BMC Neurosci 2010; 11: 57.
134. Liu Z, Yu Y, Li X, Ross CA, Smith WW. Curcumin protects against A53T alpha-synuclein-induced toxicity in a PC12 inducible cell model for Parkinsonism. Pharmacol Res 2011; 63: 439-44.
135. Ono K, Yamada M. Antioxidant compounds have potent antifibrillogenic and fibril-destabilizing effects for alpha-synuclein fibrils in vitro. J Neurochem 2006; 97: 105-15.
136. Pal R, Miranda M, Narayan M. Nitrosative stress-induced Parkinsonian Lewy-like aggregates prevented through polyphenolic phytochemical analog intervention. Biochem Biophys Res Commun 2011; 404: 324-9.
137. Sofic E, Riederer P, Heinsen H, et al. Increased iron (III) and total iron content in post mortem substantia nigra of parkinsonian brain. J Neural Transm 1988; 74: 199-205.
138. Ben-Shachar D, Zuk R, Glinka Y. Dopamine neurotoxicity: inhibition of mitochondrial respiration. J Neurochem 1995; 64: 718-23.
139. Fatih N, Camberlein E, Island ML, et al. Natural and synthetic STAT3 inhibitors reduce hepcidin expression in differentiated mouse hepatocytes expressing the active phosphorylated STAT3 form. J Mol Med 2010; 88: 477-86.
140. Messner DJ, Sivam G, Kowdley KV. Curcumin reduces the toxic effects of iron loading in rat liver epithelial cells. Liver Int 2009; 29: 63-72.
141. Dairam A, Fogel R, Daya S, Limson JL. Antioxidant and ironbinding properties of curcumin, capsaicin, and S-allylcysteine reduce oxidative stress in rat brain homogenate. J Agric Food Chem 2008; 56: 3350-6.
142. Bernabe-Pineda M, Ramirez-Silva MT, Romero-Romo MA, Gonzalez-Vergara E, Rojas-Hernandez A. Spectrophotometric and electrochemical determination of the formation constants of the complexes Curcumin-Fe(III)-water and Curcumin-Fe(II)-water. Spectrochim Acta A Mol Biomol Spectrosc 2004; 60: 1105-13.
143. Vajragupta O, Boonchoong P, Watanabe H, Tohda M, Kummasud N, Sumanont Y. Manganese complexes of curcumin and its derivatives: evaluation for the radical scavenging ability and neuroprotective activity. Free Radic Biol Med 2003; 35: 1632-44.
144. Harish G, Venkateshappa C, Mythri RB, et al. Bioconjugates of curcumin display improved protection against glutathione depletion mediated oxidative stress in a dopaminergic neuronal cell line: Implications for Parkinson's disease. Bioorg Med Chem 2010; 18: 2631-8.