姜黄素的中枢药理作用研究进展

摘要/Abstract

摘要：姜黄素（Curcumin）是从植物姜黄块根中提取的一种黄色色素，属多酚类化合物。大量已有研究证实了其在外周的药理作用，如抗动脉粥样硬化、抗肿瘤、抗糖尿病等；近年来人们发现姜黄素在中枢神经退行性疾病及精神紊乱性疾病如阿尔茨海默尔病、帕金森病、抑郁症、癫痫、焦虑等也有治疗作用。姜黄素作为一种强抗氧剂，通过调节体内氧化 - 还原平衡，减少氧化应激造成的损伤，从而发挥其神经保护作用。姜黄素的神经保护作用除了与其抗氧化作用有关外，还通过调节一系列信号蛋白如核转录因子κB（nuclear factor kapaa B，NF-κB），核因子 E2相关因子 2 （nuclear factor-erythroid 2 -related factor 2，Nrf2），磷酸化丝裂原激活 / 细胞外信号调节激酶（p-mitogen-activated/extracellular signal-regulated kinase，p-MEK），磷酸化细胞外信号调节蛋白激酶（p-extracellular regulated protein kinase, p-ERK)，原癌基因 c-fos，淀粉样前体蛋白（amyloid precursor protein，APP）, β淀粉样前体蛋白裂解酶1（β-site APP cleavage enzyme 1，BACE1）等影响BDNF/TrkB-MAPK/PI-3K-CREB 信号转导通路，提高神经元的活性和突触功能，增强神经元可塑性，减少凋亡，继而改善神经退行性疾病症状。本文综述了姜黄素在中枢神经退行性疾病和脑缺血损伤、精神紊乱性疾病如抑郁和焦虑中的作用及其机制。

关键词:姜黄素,中枢,神经保护,作用机制,进展

Abstract:Curcumin, an active yellow polyphenol pigment of turmeric, belongs to polyphone compound. Quantities of research have proved its pharmacologic actions in peripheral systems, such as antiatherosclerosis, antineoplasms, antidiabetes; In recent years, people have also found curcumin’s therapeutic effects on some neurodegenerative diseases and affective disorders, such as alzheimer’s, parkinson’s, depression, epilepsy and anxiety. As a powerful antioxidative agent, curcumin can modulate the balance of redox and reduce the formation of responsive oxidative species（ROS）, which results in the neuroprotective effect. In addition to these, the neuroprotective effect of curcumin is involved in regulating signal molecules, such as NF-κB Nrf2 p-MEK,p-ERK,c-fos,APP,BACE1.Curcumin can also affect the BDNF/TrkB-MAPK/PI-3K-CREB pathway to regulate the neuroplasticity, cell vitality and antiapoptosis. This review summarizes the effects and possible mechanism of curcumin on neurodegenerative diseases, cerebral ischemia, traumatic brain injury and affective disorders such as depression and anxiety.

Key words:curcumin,central system,neuroprotection,mechanisms,progression

中图分类号:

R285

李高文, 徐英, 库宝善, 潘建春. 姜黄素的中枢药理作用研究进展[J]. 神经药理学报, 2011, 1(2): 48-57.

LI Gao-wen, XU Ying, KU Bao-shan, PAN Jian-chun. Research Progress on Pharmacologic Actions of Curcumin in Central Nervous System[J]. ACTA NEUROPHARMACOLOGICA, 2011, 1(2): 48-57.

参考文献

1. 国家药典委员会.中华人民共和国药典（2005年版）[M].北京，化学工业出版社，2005：186.
2.Bharat B Aqqarwal，Kuzhuvelil B Harikumar. Potential therapeutic effect of curucmin，the anti-inflammatory agent，against neurodegenerative，cardiovascular，pulmonary，metabolic，autoimmune and neoplastic diseases [J]. Int J Biochem Cell Biol，2009，41（1）：40-59.
3. V Chandra，R Pandav，H H Dodge，et al. Incidence of Alzheimer's disease in a rural community in India：the Indo-US study[J]. Neurology，2001，57（6）：985-989.
4．Anna Paravhikova, Kim N Green, Curt Hendrix,et al. Formulation of a medical food cocktail for Alzheimer’s disease: beneficial effects on cognitive and neuropathology in a mouse model of the disease[J]. PLoS One,2010,5(11):e14015.
5. Reeta KH, Mehla J, Gupta YK. Curcumin ameliorates cognitive dysfunction and oxidative damage in phenobarbitone and carbamazepine administered rats[J]. Eur J Pharmacol,2010,644(1-3):106-112.
6. Ying Xu，Dan Lin，Shan Li，et al. Curcumin reverses impaired cognition and neuronal plasticity induced by chronic stress[J]. Neuropharmacology，2009, 57(4):463-471.
7. 库宝善. 神经精神药理学[M]. 第一版. 北京：北京大学医学出版社，2006：333-334.
8. M Garcia-Alloza，L A Borrelli，A Rozkalne，et al. Curcumin labels amyloid pathology in vivo，disrupts existing plaques，and partially restores distorted neurites in an Alzheimer mouse model[J]. J Neurochem，2007，102（4）：1095-1104.
9. Giselle P Lim，Teresa Chu，Fusheng Yang，et al. The curry spice curcumin reduces oxidative damage and amyloid pathology in an alzheimer transgenic mouse[J]. J Neurosci，2001，21（21）：8370-8377.
10. John M Ringman，Sally A Frautschy，Gregory M Cole，et al. A potential role of the curry spice curcumin in alzheimer’s disease[J]. Curr Alzheimer Res，2005，2（2）：131-136.
11. Salvioli S，Sikora E，Cooper E L，et al. Curcumin in cell death processes：A challenge for CAM of age-related pathologies[J]. eCAM，2007，4（2）：181-190.
12. Suh H W，Kang S，Kwon K S. Curcumin attenuates glutamate-induced HT-2 cell death by suppressing MAP kinase signaling[J]. Mol Cell Biochem，2007，298 （1 /2）：187.
13. Han-Chang Huang, Chang-Jun Lin, Wen-Juan Liu,et al. Dual effects of curcumin on neuronal oxidative stress in the presence of Cu(II) [J]. Food Chem Toxicol, 2011,49(7):1578-1583.
14. Santosh K Sandur，Haruyo Ichikawa，Manoj K Pandey，et al. Role of prooxidants and antioxidants in the anti-inflammatory and apoptotic effects of curcumin （diferuloylmethane） [J]. Free Rad Biol Med，2007，43（4）：568-580.
15. Hatcher H，Planalp R，Cho J，et al. Curcumin：From ancient medicine to current clinical trials cell [J]. Cell Mol Life Sci，2008，65(11)：1631-1652.
16. Jun Jiang，Wei Wang，Yong jun Sun，et al. Neuroprotective effect of curcumin on focal cerebral ischemic rats by preventing blood-brain barrier damage[J]. Eur J Pharmacol，2007，561（1/3）：54-62.
17. Pan Rui，Qiu Sheng，LU Da-xiang，et al. Curcumin improves learning and memory ability and its neuroprotective mechanism in mice[J]. Chin Med J，2008，121 （9）：832-839.
18. Santosh K Sandur，Manoj K Pandey，Bokyung Sung，et al. Curcumin，demethoxycurcumin，bisdemethoxycurcumin，tetrahydrocurcumin and turmerones differentially regulate anti-inflammatory and anti-proliferative responses through a ROS-independent mechanism[J]. Carcinogenesis，2007，28（8）：1765-1773.
19. Maria M LoTempio，Mysore S Veena，Helen L Steele，et al. Curcumin suppresses growth of head and neck squamous cell carcinoma[J]. Cancer Res，2005，11（19）：6994-7002.
20. Bharat B Aggarwal，Kuzhuvelil B Harikumar. Potential therapeutic effects of curcumin，the anti-inflammatory agent，against neurodegenerative，cardiovascular，pulmonary，metabolic，auto-immune and neoplastic diseases[J]. Int J Biochem Cell Biol，2009，41（1）：40-59.
21. Wang HM，Zhao YX，Zhang S，et al. PPAR gamma agonist curcumin reduces the amyloid-beta-stimulated inflammatory responses in primary astrocytes[J].J Alzheimers Dis，2010，20（4）：1189-1199.
22．H.P. Rang, M.Maureejn.Dale, James M.Ritter,et al. Rang and Dale’s Pharmacoogy[M]. sixth edition.London:ELSEVIER,2007,514-520.
23. Bossy-Wetzel E, Schwarzenbacher R, Lipton SA. Molecular pathways to neurodegeneration[J].Nat Med,2004, 10(suppl):S2-S9.
24. H Hatcher，R Planalp，J Cho，et al. Curcumin：From ancient medicine to current clinical trials.[J]. Cell Mol Life Sci，2008，65（11）：1631-1652.
25. Can Zhang ，Andrew Browne，Daniel Child，Rudolph E Tanzi . Curcumin decreases amyloid-beta peptide levels by attenuating the maturation of amyloid-beta precursor protein[J]. J Biol Chem，2010，285（37）：28472-28480.
26. Raozhou Lin，Xiaohong Chen，Wenming Li，et al. Exposure to metal ions regulates mRNA levels of APP and BACE1 in PC12 cells：Blockage by curcumin[J]. Neurosci Lett，2008，440（3）：344-347.
27.Shimmyo Yoshiaria, Kihara Takeshia, Akaike Akinorib,et al. Epigallocatechin-3-gallate and curcumin suppress amyloid beta-induced beta-site APP cleaving enzyme-1 upregulation[J]. Neuroreport,2008,19(13):1329-1333.
28. Liu H, Li Z,Qiu D,et al. The inhibitory effects of different currcuminoids onβ-amyloid protein, β-amyloid precursor protein and β-site amyloidprecursor protein cleaving enzyme 1 in swAPP HEK293 cells[J]. Neurosci Lett,2010,485(2):83-88.
29. 于嵩. 姜黄素对PD病和阿尔茨海默尔病神经元保护作用的实验研究[D]. 北京，中国医科大学，2010.
30.Jing Zhao，Yong Zhao，Weiping Zheng，et al. Neuroprotective effect of curcumin on transient focal cerebral ischemia in rats[J]. Brain Res，2008，1229：224-232.
31. 廖涛，王飞，张占军，等. 姜黄素对痴呆模型小鼠学习记忆能力的改善作用及对细胞凋亡影响[J]. 中国药理学通报，2009,25（10）：1359-1363.
32. Anil Kamar, Atish Prakash , Samrita Dogra. Protective effect of curcumin(curcuma longa) against D-galactose-induced senescence in mice[J]. J Asian Nat Prod Res,2011, 13(1):42-55.
33. Dong Jun, Qiu Sheng, Lu Da-Xiang,et al. Effect of curcumin on scopolamine-induced memory impairment in mice[J]. Chinese Journal of Pathophysiology,2009,25(1):112-117.
34. Puneet Rinawa, Baljinder Kaur, Amteshwar Sing Jaqqi,et al. Involvement of PPAR-gamma in curcumin-mediated beneficial effects in experimental dementia[J]. Naunyn Schmiedebergs Arch Pharmacol,2010,381(6):529-539.
35. Kuhad A, Chopra K. Curcumin attenuates diabetic encephalopathy in rats:behavioral and biochemical evidences[J]. Eur JPharmacol,2007,576(1-3):34-42.
36. Anil Kumar，Nadiu P S，Seghal N，et al. Effect of curcumin on intracerebroventricular colchicine-induced cognitive impairment and oxidative stress in rats[J]. Med Food，2007，10（3）：486-494.
37. Ying Xu，Bao-shan Ku，Hai-Yan Yao，et al. The effects of curcumin on depressive-like behaviors in mice[J]. Eur J Pharmacol，2005，518(1)：40-46.
38.Ying Xu，Bao-shan Ku ，Hai-Yan Yao，et al. Antidepressant effects of curcumin in the forced swim test and olfactory bulbectomy models of depression in rats[J]. Pharmacol Biochem Behav，2005，82(1)：200-206.
39. Zhao Wei-Qin，Fernanda G De Felice，Sara Fernandez，et al. Amyloid beta oligomers induce impairment of neuronal insulin receptors[J]. Faseb J，2008，22 （1）：246.
40. Oleg Butovsky，Maya Koronyo-Hamaoui，Gilad Kunis，et al. Glatiramer acetate fights against Alzheimer’s disease by inducing dendritic-like microglia expressing insulin-like growth factor 1[J]. PNAS，2006，103（31）：11784.
41. Ahmet Turan Isik , Turgay Celik , Gokan Ulusoy，et al.Curcumin ameliorates impaired insulin/IGF signalling and memory deficit in a streptozotocin-treated rat model[J]. AGE，2009，31（1）：39-49.
42. Touqeer Ahmed , Anwarul-Hassan Gilani, Narges Hosseinmardin,et al. Curcuminoids rescue long-term protentation impaired by amyloid peptide in rat hippocampal slices[J]. Synapse, 2011, 65(7):572-582.
43. Hongmei Tang, Daxiang Lu, Rui Pan，et al. Curcumin improves spatial memory impairment induced by human immunodeficiency virus type 1 glycoprotein 120 V3 loop peptide in rats[J]. Life Sci, 2009, 85(1-2):1-10.
44. Ahmed T,Enam SA,Gilani AH. Curcuminoids enhance memory in an amyloid-infused rat model of Alzheimer's disease[J].J Neurosci,2010,169(3):1296-1306.
45. 孙臣友，戚双双，孙淑红，等. 姜黄素对快速老化小鼠学习与记忆功能及海马Ca²⁺/CaMKII水平的影响[J]. 中国中西医结合杂志，2011，3（31）：376-380.
46. Li YY，Cui JG，Hill JM，et al. Increased expression of miRNA-146a in Alzheimer's disease transgenic mouse models[J]. Neurosci Lett，2011，487（1）：94-98.
47. Yamaratee Jaisin, Anusorn Thampithak, Benjawan Meesarapee,et al. Curcumin I protects the dopaminergic cell line SH-SY5Y from 6-hydroxydopamine-induced neurotoxicity through attenuation of p53-mediated apoptosis[J].Neurosci Lett,2011,489(3):192-196.
48. Gulrana Khuwaja, Mohd Moshahid Khan, Tauheed Ishrat. Neuroprotective effects of curcumin on 6-hydroxydopamine-induced Parkinsons’ in rats: behavioral, neurochemical and immunohistochemical studies[J]. Brain Res, 2011,1368:254-263.
49. Sufen Yang，Dan Zhang，zhengqin Yang，et al. Curcumin protects dopaminergic neuron against LPS induced neurotoxicity in primary rat neuron/glia culture[J]. Neurochem Res，2008，33（10）：2044-2053.
50. 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[J]. Inflammopharmacology，2008，16（2）：96-99.
51. Mahendra Bishnoi, Kanwalijit Chopra ,Shrinivas K Kulkarni. Protective effects of Curcumin,the active principle of turmeric(Curcuma longa) in haloperidol-induced orofacial dyskinesia and associated behavioural,biochemical and neurochemical changes in rat brain[J]. Pharmacol Biochem Behav,2008,88(4):511-522.
52. Nidhi Bharal Agarwal, Seema Jain, Nitin K Agarwal,et al. Modulation of pentylenetetrazole-induced kindling andoxidative stress by curcumin in mice[J]. Phytomedicine（2011），18(8-9):756-759.
53. Jogender Mehla, K H Reeta, Pooja Gupta ,et al. Protective effects of curcumin against seizares and congnitive impairment in a pentylenetetrazole-kindled epileptic rat model[J]. Life Sci, 2010,89(9-22):596-603.
54. Hyun Joo Shin，Ji Yeong Lee，Eunyung Son，et al. Curcumin attenuates the kainic acid induced hippocampal cell death in the mice[J]. Neurosci Lett，2007，416（1）：49-54.
55. Reeta KH, Jogender Mehla, Monika Pahuja,et al. Pharmacokinetic and pharmacodynamic interactions of valproate, phenytoin, phenobarbitone and carbamazepine with curcumin in experimental models of epilepsy in rats.[J] Pharmacol Biochem Behav,2011, 99(3):399-407
56. Marie Naughton，Jane Mulrooney，Brian E Leonard. A review of the role of serotonin receptors in psychiatric disorders[J]. Hum.Psychopharmacol Clin Exp，2000，15(6)：397-415.
57. Abdalla Salem Elhwuegi. Central monoamines and their role in major depression[J]. Prog Neuro-Psychopharmacol，2004，28(3)：435-451.
58. Pierre Blier，Claude De Montigny. Current advances and trends in the treatment of depression[J]. Trends Pharmacol. Sci，1994，15(7)：220-226.
59. Reul JM，Labeur MS，Grigoriadis DE，et al. Hypothalamic pituitary adrenocortical axis changes in the rat after long-term treatment with the reversible monoamine oxidase-A inhibitor moclobemide[J]. Neuroendocrinology，1994，60(5)：509-519.
60. Z.F.Yu，L.D.Kong，Y.Chen. Antidepressant activity of aqueous extracts of Curcuma longa in mice[J]. Journal of Ethnopharmacology，2002，83(1-3)：161-165.
61. Mohit Kumar Bhutani, Mahendra Bishnoi, Shrinivas K Kulkarni. Antidepressant like effects of curcumin and its combination with piperine in unpredictable chronic stress-induced behavioral, biochemical and neurochemical changes[J]. Pharmacol Biochem Behav, 2009,92(1):39-43.
62. Ying Xu，Bao-Shan Ku，Hai-Yan Yao，et al. The effects of curcumin on depressive-like behaviors in mice[J]. Eur J Pharmacol，2005，518：40-46.
63.Shrinivas K Kulkarni，Mohit Kumar Bhutani，Mahendra Bishnol，et al.Antidepressant activity of curcumin:involvement of serotonin and dopamine system[J]. Psychopharmacology，2008，201(3)：435-442.
64. Rui Wang，Ying Xu，Hong-Li Wu，et al. The antidepressant effects of curcumin in the forced swimming test involve 5-HT1 and 5-HT2 receptors[J]. Eur J pharmcol，2008，578(1)：43-50.
65. Matthew J Bair, Rebecca L Robinson, Wayne Katon,et al. Depression and pain comorbidity:a literature review[J]. Arch Intern Med,2003,163:2433-2445.
66. Bruce A Arnow, Enid M Hunkeler, Chirstine M Blasey,et al. Comorbid depression, chronic pain, and disability in primary care[J]. Psychosom Med,2006,68:262-268.
67. Ferrer-Garcia MD, Wernicke JF, Detke MJ,et al. The depression-pain complex:overlap between the two problems and implications for neuropathic pain[J]. 2006. IASP Press, Seattle, pp:307-325.
68. Arora V, Kuhad A, Tiwari V,et al. Curcumin ameliorates reserpine-induced pain-depression dyad:Behavioural, biochemical, neurochemical and molecular evidences[J]. Psychoneuroendocrinology,2011,Nov;36(10):1570-81.
69.Zobel AW，Nickel T,Kunzel HE,et al. Effects of the high-affinity corticotrophin-releasing hormone receptor I antagonist R121919 in major depression:the first 20 patients treated[J]. Psychiatr Res，2000，34(3)：171-181.
70. F Holsboer. Stress,hypercortisolism and corticosteroid receptors in depression：implications for therapy[J]. Affect Disord，2001，62：77-91.
71. Ana Maria Magarinos，Bruce S McEwen，Gabriele Flugge，et al. Chronic psychosocial stress causes apical dendritic atrophy of hippocampal CA3 pyramidal neurons in subordinate tree shrews[J]. Neurosci，1996，16(10)：3534-3540.
72. Sapolsky R, Krey LC, McEwen BS. The neuroendocrinology of stress and aging: the glucocorticoid cascade typothesis[J]. Endocrine Research,1986,7:284-301.
73. Nuno Sousa, Joao J Cerqueira, Osbrone F X Almeida. Corticosteroid receptors and neuroplasticity[J]. Brain Research Reviews, 2008, 57:561-570.
74. Ajai Vyas, Rupshi Mitra, B S Shankaranarayana Rao,et al. Chronic stress induces contrasting patterns of dendritic remodeling in hippocampal and amygdaloid neurons[J]. Journal of Neuroscience, 2002, 22:6810-6818.
75. Ying Xu，Baoshan Ku，Lu Tie，et al. Curcumin reverses the effects of chronic stress on behavior,the HPA axis,BDNF expression and phosphorylation of CREB[J]. Brain Res，2005，1122：56-64.
76. 陈亮，吕平，潘建春，等. 姜黄素对慢性应激大鼠肾上腺、血清ACTH 和免疫功能的影响[J]. 温州医学院学报，2008，38（1）：22-24.
77. Reines A, Cereseto M, Ferrero A,et al. Maintenance treatment with fluoxetine is necessary to sustain normal levels of synaptic markers in an experimental model of depression:correlation with behavioral response[J]. Neuropsychopharmacology, 2008, 33:1896-1908.
78. Yvette I Sheline, Mokhtar H Gao, Helena C Kraemer. Untreated depression and hippocampal volume loss[J]. Am J Psychiatry，2003，160：1516–1518.
79. DA Seminowicz, HS Mayberg, AR Mclntosh,et al. Limbic-frontal circuitry in major depression：a path modeling metanalysis[J]. Neuroimage，2004，22：409–418.
80. Neumeister A. Neural and behavioral responses to tryptophan depletion in unmedicated patients with remitted major depressive disorder and controls[J]. Arch Gen Psychiatry，2004，61：765–773.
81.Mounira Banasr, Micheline Hery, Richard Printemps,et al. Serotonin-induced increases in adult cell proliferation and neurogenesis are mediated through different and common 5-HT receptor subtypes in the dentate gyrus and the subventricular zone[J]. Neuropsychopharmacology，2004，29：450–460.
82.Ying Xu，Baoshan Ku，Li Cui，et al. Curcumin reverses impaired hippocampal neurogenesis and increases serotonin receptor 1A mRNA and brain-derived neurotrophic factor expression in chronically stressed rats[J]. Brain Res，2007，8(1162)：9-18.
83. Smith MA，Makino S，Kvetnansky R，et al. Stress and glucocorticoids affect the expression of brain-derived neurotrophic factor and neurotrophin-3 mRNAs in the hippocampus[J]. Neurosci，1995，15：1768-1777.
84. Huang Zhen, Xiao-Ming Zhang, Zhao-Yi Li . Curcumin reverses corticosterone-induced depressive-like behavior and decrease in brain BDNF levels in rats[J]. NeuroSci Lett, 2011, 493(3):145-148.
85. Rui Wang，Ying-Bo Li，Yu-Hua Li，et al. Curcumin protects against glutamate excitotoxicity in rat cerebral cortical neurons by increasing brain-derived neurotrophic factor level and activating TrkB[J]. Brain Research，2008，1210：84-91.
86.Yu-Cheng Li，Fu-Meng Wang，Ying Pan，et al. Antidepressant effects of curcumin on serotonergic receptor-coupled AC-cAMP pathway in chronic unpedictable mild stress of rats[J].Prog Neuro-Psychoph，2009，33：435-449.
87. 王任烨，徐英，蒋文高，等. 姜黄素对慢性应激大鼠不同脑区cAMP水平及腺苷酸环化酶活性的影响[J]. 中国药学杂志，2007，42（2）：121-124.
88.Rui Wang,Yu-Hua Li,Ying Xu,et al. Curcumin produces neuroprotective effects via activating brain-derived neurotrophic factor/TrkB-dependent MAPK and PI-3K cascades in rodent cortical neurons[J]. Prog Neuropsychopharmacol Biol Psychiatry, 2010, 34(1):147-153.
89. Ying Xu，Dan Lin，Shan Li，et al. Curcumin reverses impaired cognition and neuronal plasticity induced by chronic stress[J]. Neuropharmacology, 2009,57(4):463-471.
90. Matteucci A, Cammarota R, Paradisis,et al.Curcumin protects against NMD-induced toxicity: a possible role for NR2A subunit[J].Invest Ophthalmol Vis Sci, 2011, 52(2):1070-1077.
91. Catherine Heurteaux, Guillaume Lucas, Nicolas Guy,et al. Deletion of the background potassium channel TREK-1 results in a depression-resistant phenotype[J]. Nat Neurosci,2006,9(9):1134-1141.
92. Xi Guangjun, Zhang Xiangrong, Zhang Ling,et al. Fluxetine attenuates the inhibitory effect of glucocorticoid hormones on neurogenesis in vitro via a two-pore domain potassium channel,TREK-1 [J].Psychopharmacology(Berl), 2011, 214(3):747-759.
93. 马行，徐英，姚海燕，等. 姜黄素对慢性应激大鼠不同脑区促肾上腺皮质激素释放因子表达的影响[J]. 中国药理学与毒理学杂志,2006,20(6):468-472.
94. Neeraj Gilhotra, Dinesh Dhingra . GABAergic and nitriergic modulation by curcumin for its antianxiety-like activity in mice[J]. Brain Res, 2010, 17(1352):167-75.
95.Anil Kumar, Anant Singh . Possible nitric oxide modulation in protective effect of (Curcuma longa, Zingiberaceae) against sleep deprivation-induced behavioral alterations and oxidative damage in mice[J]. Phytomedicine, 2008, 15(8):577-86.
96. Thomas J Connor，Brian Leonard. Depression，stress and immunological activation: the role of cytokines in depressive disorders[J]. Life Sci，1998，62(7)：583-606.
97. Xueting Mei , Donghui Xu, Sika Xu,et al. Gastroprotective and antidepressant effects of a new zinc(II)-curcumin complex in rodent models of gastric ulcer and depression induced by stresses[J]. Pharmacol Biochem Behav, 2011, 99(1):66-74.
98. Pradeep K Shukla, Vinay K Khanna, Mohd M Ali ,et al. Anti-ischemic effects of curcumin in rat brain[J]. Neurochem Res,2008,33(6):1036-1043.
99. Chenhui Yang,Xiangjian Zhang,Hongguang Fan,et al. Curcumin upregulates transcription factor Nrf2,HO-1 expression and protects rat brains against focal ischemia[J]. Brain Res,2009,1282:133-141.
100. Yuan-Yuan Zheng,Lin-Sheng Yu,Yi-Gu Zhang,et al. Effects of curcumin on malondialdehyde and c-fos protein in hypoxia ischemia brain tissue in rats[J]. Fa Yi Xue Za Zhi,2009,25(1):6-8.
101.Preeti Dohare ,Puja Garg,Vikas Jain,et al. Dose dependence and therapeutic window for the neuroprotective effects of curcumin in thromboembolic model of rat[J]. Behav Brain Res,2008.193(2):289-297.
102. Qun Wang,Albert Y Sun ,Agnes Simonyi ,et al. Neuroprotective mechanisms of curcumin aginst cerebral ischemia-induced neuronal apoptosis and behavioral deficits[J]. J Neurosci Res,2005,82(1):138-148.
103. Jing Zhao,Shanshan Yu,Weiping Zheng,et al. Curcumin improves outcomes and attenuates focal cerebral ischemic injury via antiapoptotic mechanisms in rats[J]. Neurochem Res,2010,35(3):374-379.
104. Jing Zhao, Yong Zhao,Weiping Zheng,et al. Neuroprotective effect of curcumin on transient focal cerebral ischemia in rats[J]. Brain Res,2008,1229:224-232.
105.Aiguo Wu, Zhe Ying,David Schubert,et al. Brain and spinal cord interaction:a dietary curcumin derivative counteracts locomotor and cognitive deficits after brain trauma[J].Neurorehab Neural re,2011,25(4):332-342.
106. Aiguo Wu,Zhe Ying,Fermando Gomez-Pinilla. Dietary curcumin counteracts the outcome of traumatic brain injury on oxidative stress,synaptic plasticity,and cognition[J]. Exp Neurol,2006,197(2):309-317.
107. Sharma S,Zhang Y,Ying Z,et al. Dietary curcumin supplementation counteracts reduction in levels of molecules involved in energy homeostasis after brain trauma[J]. Neuroscience,2009,161(4):1037-11044.
108. Rosenbaum JF, Covino JM. Advances in the treatment of depression program and abstract of the American Psychiatric Association 158^thnnual Meeting. Atlanta, 2005,21-26.
109. Yan Jiao，John Wilkinson IV，Xiumin Di ，et al. Curcumin，a cancer chemopreventive and chemotherapeutic agent，is a biologically active iron chelator[J]. Blood，2009，113：462-469.
110. Ray B, Bisht S, Maitra A,et al. Neuroprotective and neurorescue effects of a novel polymeric nanmparticle formation of curcumin(NanoCur^TM) in the neuronal cell culture and animal model: implication for Alzheimer’s disease[J]. J Alzheimer’s Dis, 2011,23(1):61-77.

[1]	赵雨薇, 甄艳杰, 戴月英, 沈丽霞.槲皮素对阿尔茨海默症神经保护作用研究[J]. 神经药理学报, 2020, 10(5): 55-64.
[2]	刘杉, 李炜.L- 茶氨酸药理作用的研究进展[J]. 神经药理学报, 2020, 10(2): 24-32.
[3]	钟伟权, 刘佑波, 周才杰, 郑银驹, 邬明利, 梁敏, 张媛媛.基于网络药理学探讨人参有效成分对骨关节炎的保护作用机制研究[J]. 神经药理学报, 2020, 10(1): 10-16.
[4]	郑贝贝, 冯硕, 郭梦圆, 冯璞, 岑娟, 张峰.反应氧族促进血管生成的作用及其脑内意义[J]. 神经药理学报, 2020, 10(1): 24-28.
[5]	甄艳杰, 郭童林, 赵雨薇, 沈丽霞.植物雌激素介导线粒体途径对阿尔茨海默病神经保护作用的研究进展[J]. 神经药理学报, 2020, 10(1): 40-46.
[6]	杨靖，苑文英.弓形虫感染对神经组织损伤及通过血脑屏障机制[J]. 神经药理学报, 2019, 9(5): 40-43.
[7]	吴县，洪浩.胆汁酸及其受体与中枢神经系统疾病[J]. 神经药理学报, 2019, 9(1): 23-30.
[8]	魏珍珍，方晓艳，白明，苗明三.基于星形胶质细胞的脑缺血损伤治疗研究进展[J]. 神经药理学报, 2019, 9(1): 36-43.
[9]	李江曼，王一頔，王风萍，李炜.脑缺血再灌注损伤及其星形胶质细胞相关机制研究进展[J]. 神经药理学报, 2017, 7(6): 50-59.
[10]	任婧，张丹参.姜黄素纳米剂型及在神经系统疾病中应用的研究进展[J]. 神经药理学报, 2017, 7(5): 45-51.
[11]	张佳琳，李元元，杨文亮，刘富甲，田子夏，谢欣梅，庞晓斌.黄芪甲苷基于PI3K/Akt/Bcl-2 信号通路对PC12 细胞OGD/R 损伤的保护机制研究[J]. 神经药理学报, 2017, 7(5): 1-9.
[12]	袁莉，王会荣，滕金亮.右美托咪定的作用机制及在临床麻醉中的应用[J]. 神经药理学报, 2017, 7(4): 26-30.
[13]	余汇，钟佳宏，钟秋萍，汪海涛，王文雅，徐江平.Tideglusib 对MPP+ 诱导的SH-SY5Y 细胞凋亡的保护作用及其机制研究[J]. 神经药理学报, 2017, 7(2): 61-61.
[14]	苏晓梅，张丹参.人参皂苷-Rg3 的药理作用研究进展[J]. 神经药理学报, 2017, 7(1): 38-44.
[15]	张春华，赵靖敏.生物碱类镇静催眠的化学成分及作用机制研究[J]. 神经药理学报, 2016, 6(5): 34-38.