The role of phytochemicals in the treatment and prevention of dementia

Drugs and Aging

Volumn 28, Issue 6, 2011, Pages 439-468

  Howes, Melanie Jayne R ^a   Perry, Elaine ^b  

^a JODRELL LABORATORY   (United Kingdom)

^b NEWCASTLE UNIVERSITY   (United Kingdom)

Author keywords

Alzheimers disease; Cannabinoids; Curcumin; Dementia; Galantamine; Ginkgo biloba; Huperzine A; Huperzine B; Nicotine; Physostigmine; Phytotherapies; Resveratrol

Indexed keywords

ANTIINFLAMMATORY AGENT; APOPTOSIS INHIBITOR; CANNABINOID; CHOLINESTERASE INHIBITOR; CROCUS SATIVUS EXTRACT; CURCUMIN; DONEPEZIL; GALANTAMINE; GINKGO BILOBA EXTRACT; GINSENG EXTRACT; HUPERZINE A; MELISSA OFFICINALIS EXTRACT; MEMANTINE; MONOAMINE OXIDASE A INHIBITOR; NEUROPROTECTIVE AGENT; NICOTINE; PHYSOSTIGMINE; PLANT MEDICINAL PRODUCT; POLYPHENOL; RESVERATROL; RIVASTIGMINE; ROSMARINIC ACID; SALVIA OFFICINALIS EXTRACT; VINCA ALKALOID;

ALCOHOL CONSUMPTION; AMYLOIDOSIS; APOPTOSIS; AROMATHERAPY; BLOOD PRESSURE REGULATION; CELL DEGENERATION; CELL LOSS; CEREBROVASCULAR DISEASE; CHOLINERGIC SYSTEM; COGNITION; DEMENTIA; DIABETES MELLITUS; DISEASE COURSE; DOPAMINERGIC NERVE CELL; DRUG EFFICACY; DRUG SAFETY; EXCITOTOXICITY; GASTROINTESTINAL SYMPTOM; HUMAN; INFLAMMATION; KOREAN MEDICINE; MEMORY DISORDER; NERVE CELL PLASTICITY; NERVOUS SYSTEM DEVELOPMENT; NEUROPROTECTION; NEUROTRANSMISSION; NONHUMAN; OXIDATIVE STRESS; PHASE 3 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; PROTEIN AGGREGATION; REVIEW; SEROTONINERGIC NERVE CELL; TREATMENT PLANNING; UNSPECIFIED SIDE EFFECT;

ALKALOIDS; ANIMALS; DEMENTIA; HUMANS; PHENOLS; PHYTOTHERAPY; PLANT EXTRACTS; PLANTS;

EID: 79958274796     PISSN: 1170229X     EISSN: 11791969     Source Type: Journal    
DOI: 10.2165/11591310-000000000-00000     Document Type: Review

References (301)

1. Luengo-Fernandez, Leal J, Gray A. Dementia 2010. Health Economics Research Centre, University of Oxford for the Alzheimer's Research Trust [online]. Available from URL: http://www.dementia2010.org/[Accessed 2010 Nov 29]
2. Kovacs GG, Alafuzoff I, Al-Sarraj S, et al. Mixed brain pathologies in dementia: the BrainNet Europe consortium experience. Dement Geriatr Cogn Disord 2008; 26 (4): 343-50
3. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders (4th edition). Arlington, US: American Psychiatric Publishing Inc., 2000
4. Cummings JL. Dementia with Lewy bodies: molecular pathogenesis and implications for classification. J Geriatr Psychiatry Neurol 2004; 17 (3): 112-9 (Pubitemid 39128220)
5. Desmond DW. Vascular dementia. Clin Neurosci Res 2004; 3 (6): 437-48 (Pubitemid 38684192)
6. McKeith I, Cummings J. Behavioural changes and psychological symptoms in dementia disorders. Lancet Neurol 2005; 4 (11): 735-42 (Pubitemid 41457289)
7. Luque FA, Jaffe SL. The molecular and cellular pathogenesis of dementia of the Alzheimer's type: an overview. Int Rev Neurobiol 2009; 84: 151-65
8. Panza F, Solfrizzi V, Frisardi V, et al. Beyond the neurotransmitter- focused approach in treating Alzheimer's disease: drugs targeting b-amyloid and tau protein. Aging Clin Exp Res 2009; 21 (6): 386-406
9. Sabbagh MN. Drug development for Alzheimer's disease: where are we now and where are we headed? Am J Geriatr Pharmacother 2009; 7 (3): 167-85
10. Bonda DJ, Lee HP, Lee H-G, et al. Novel therapeutics for Alzheimer's disease: an update. Curr Opin Drug Discov Devel 2010; 13 (2): 235-46
11. PogaćićKramp V, Herrling P. List of drugs in development for neurodegenerative diseases: update for June 2010. Neurodegener Dis 2011; 8 (1-2): 44-94
12. Williams P, Sorribas A, Howes M-JR. Natural products as a source of Alzheimer's drug leads. Nat Prod Rep 2011; 28 (1): 48-77
13. Matsuzaki K, Noguch T, WakabayashiM, et al. Inhibitors of amyloid b-protein aggregation mediated by GM1- containing raft-like membranes. Biochim Biophys Acta 2007; 1768 (1): 122-30 (Pubitemid 44909079)
14. Ono K, Hasegawa K, Naiki H, et al. Anti-amyloidogenic activity of tannic acid and its activity to destabilize Alzheimer's b-amyloid fibrils in vitro. Biochim Biophys Acta 2004; 1690 (3): 193-202 (Pubitemid 39423614)
15. Shimmyo Y, Kihara T, Akaike A, et al. Epigallocatechin- 3-gallate and curcumin suppress amyloid b-induced b-site APP cleaving enzyme-1 upregulation. Neuroreport 2008; 19 (13): 1329-33
16. Choi SH, Hur JM, Yang EJ, et al. b-Secretase (BACE1) inhibitors from Perilla frutescens var. acuta. Arch Pharm Res 2008; 31 (2): 183-7
17. Jung HA, Jin SE, Choi RJ, et al. Anti-amnesic activity of neferine with antioxidant and anti-inflammatory capacities, as well as inhibition of ChEs and BACE1. Life Sci 2010; 87 (13-14): 420-30
18. Jung HA, Min BS, Yokozawa T, et al. Anti-Alzheimer and antioxidant activities of Coptidis Rhizoma alkaloids. Biol Pharm Bull 2009; 32 (8): 1433-8
19. Patil SP, Maki S, Khedkar SA, et al. Withanolide A and asiatic acid modulate multiple targets associated with amyloid-b precursor protein processing and amyloid-b protein clearance. J Nat Prod 2010; 73 (7): 1196-202
20. Strong C, Anderton BH, Perry RH, et al. Abnormally phosphorylated tau protein in senile dementia of Lewy body type and Alzheimer disease: evidence that the disorders are distinct. Alzheimer Dis Assoc Disord 1995; 9 (4): 218-22 (Pubitemid 26007408)
21. Saddichha S, Pandey V. Alzheimer's and non-Alzheimer's dementia: a critical review of pharmacological and nonpharmacological strategies. Am J Alzheimers Dis Other Demen 2008; 23 (2): 150-61 (Pubitemid 351550914)
22. Zeng K-W, Ko H, Yang HO, et al. Icariin attenuates b-amyloid-induced neurotoxicity by inhibition of tau protein hyperphosphorylation in PC12 cells. Neuropharmacology 2010; 59 (6): 542-50
23. Park YJ, Jang YM, Kwon YH. Isoflavones prevent endoplasmic reticulum stress-mediated neuronal degeneration by inhibiting tau hyperphosphorylation in SH-SY5Y cells. J Med Food 2009; 12 (3): 528-35
24. Ho L, Yemul S, Wang J, et al. Grape seed polyphenolic extract as a potential novel therapeutic agent in tauopathies. J Alzheimers Dis 2009; 16 (2): 433-9
25. Fang J, Liu R, Tian Q, et al. Dehydroevodiamine attenuates calyculin A-induced tau hyperphosphorylation in rat brain slices. Acta Pharmacol Sin 2007; 28 (11): 1717-23 (Pubitemid 350029327)
26. Zeng YQ, Chen XC, Zhu YG, et al. Ginsenoside Rb1 attenuates b-amyloid peptide 25-35-induced tau hyperphosphorylation in cortical neurons. Yao Xue Xue Bao 2005; 40 (3): 225-30
27. Kim HS, Sul D, Lim JY, et al. Delphinidin ameliorates b-amyloid-induced neurotoxicity by inhibiting calcium influx and tau hyperphosphorylation. Biosci Biotechnol Biochem 2009; 73 (7): 1685-9
28. Rezai-Zadeh K, Arendash GW, Hou H, et al. Green tea epigallocatechin-3- gallate (EGCG) reduces b-amyloid mediated cognitive impairment and modulates tau pathology in Alzheimer transgenic mice. Brain Res 2008; 1214: 177-87
29. Francis PT, Ramez MJ, Lai MK. Neurochemical basis for symptomatic treatment of Alzheimer's disease. Neuropharmacology 2010; 59 (4-5): 221-9
30. Klein JC, Eggers C, Kalbe E, et al. Neurotransmitter changes in dementia with Lewy bodies and Parkinson disease dementia in vivo. Neurology 2010; 74 (11): 885-92
31. Xiao Q, Wang C, Li J, et al. Ginkgolide B protects hippocampal neurons from apoptosis induced by b-amyloid 25-35 partly via up-regulation of brain-derived neurotrophic factor. Eur J Pharmacol 2010; 647 (1-3): 48-54
32. Choi JH, Choi AY, Yoon H, et al. Baicalein protects HT22 murine hippocampal neuronal cells against endoplasmic reticulum stress-induced apoptosis through inhibition of reactive oxygen species production and CHOP induction. Exp Mol Med 2010; 42 (12): 811-22
33. Zhang H, Liu Y, Lao M, et al. Puerarin protects Alzheimer's disease neuronal cybrids from oxidant-stress induced apoptosis by inhibiting pro-death signaling pathways. Exp Gerontol 2011; 46 (1): 30-7
34. Liu X, Xu K, Yan M, et al. Protective effects of galantamine against Ab-induced PC12 cell apoptosis by preventing mitochondrial dysfunction and endoplasmic reticulum stress. Neurochem Int 2010; 57 (5): 588-99
35. Choi AY, Choi JH, Lee JY, et al. Apigenin protects HT22 murine hippocampal neuronal cells against endoplasmic reticulum stress-induced apoptosis. Neurochem Int 2010; 57 (2): 143-52
36. Geng Y, Li C, Liu J, et al. b-Asarone improves cognitive function by suppressing neuronal apoptosis in the b-amyloid hippocampus injection rats. Biol Pharm Bull 2010; 33 (5): 836-43
37. Jang YJ, Kim JE, Kang NJ, et al. Piceatannol attenuates 4-hydroxynonenal-induced apoptosis of PC12 cells by blocking activation of c-Jun N-terminal kinase. Ann N Y Acad Sci 2009; 1171: 176-82
38. Cho ES, Jang YJ, Hwang MK, et al. Attenuation of oxidative neuronal cell death by coffee phenolic phytochemicals. Mutat Res 2009; 661 (1-2): 18-24
39. Cho ES, Lee KW, Lee HJ. Cocoa procyanidins protect PC12 cells from hydrogen-peroxide-induced apoptosis by inhibiting activation of p38 MAPK and JNK. Mutat Res 2008; 640 (1-2): 123-30
40. Court JA, Perry EK. Dementia: the neurochemical basis of putative transmitter orientated therapy. Pharmacol Ther 1991; 52 (3): 423-43
41. Khan I, Nisar M, Khan N, et al. Structural insights to investigate conypododiol as a dual cholinesterase inhibitor from Asparagus adscendens. Fitoterapia 2010; 81 (8): 1020-5
42. Howes M-JR, Houghton PJ. Acetylcholinesterase inhibitors of natural origin. Int J Biomed Pharm Sci 2009; 3 (SI 1): 67-86
43. Daly JW. Nicotinic agonists, antagonists, and modulators from natural sources. Cell Mol Neurobiol 2005; 25 (3-4): 513-52 (Pubitemid 41199710)
44. Chandler CJ, Stolerman IP. Discriminative stimulus properties of the nicotinic agonist cytisine. Psychopharmacology 1997;129(3) 257-64 (Pubitemid 27085396)
45. Niu YY, Yang LM, Liu HZ, et al. Activity and QSAR study of baogongteng A and its derivatives as muscarinic agonists. Bioorg Med Chem Lett 2005; 15 (21): 4814-8
46. Mossner R, Schmitt A, Syagailo Y, et al. The serotonin transporter in Alzheimer's and Parkinson's disease. J Neural Transm Suppl 2000; (60): 345-50 (Pubitemid 32037205)
47. Perry E, Howes M-JR. Medicinal plants and dementia therapy: herbal hopes for brain aging? CNS Neurosci Ther. Epub 2010 Oct 18
48. Michel JL, Chen Y, Zhang H, et al. Estrogenic and serotonergic butenolides from the leaves of Piper hispidum Swingle (Piperaceae). J Ethnopharmacol 2010; 129 (2): 220-6
49. Sugimoto Y, Furutani S, Nishimura K, et al. Antidepressant- like effects of neferine in the forced swimming test involve the serotonin1A (5-HT1A) receptor in mice. Eur J Pharmacol 2010; 634 (1-3): 62-7
50. Zhao G, Gai Y, Chu WJ, et al. A novel compound N1, N5- (Z)-N10-(E)-tri-p-coumaroylspermidine isolated from Carthamus tinctorius L. and acting by serotonin transporter inhibition. Eur Neuropsychopharmacol 2009; 19 (10): 749-58
51. Machado DG, Bettio LEB, Cunha MP, et al. Antidepressant- like effect of rutin isolated from the ethanolic extract from Schinus molle L. in mice: evidence for the involvement of the serotonergic and noradrenergic systems. Eur J Pharmacol 2008; 587 (1-3): 163-8
52. Ren L-X, Luo Y-F, Li X, et al. Antidepressant-like effects of sarsasapogenin from Anemarrhena asphodeloides Bunge (Liliaceae). Biol Pharm Bull 2006; 29 (11): 2304-6 (Pubitemid 44690962)
53. Both FL, Meneghini L, Kerber VA, et al. Psychopharmacological profile of the alkaloid psychollatine as a 5HT2A/C serotonin modulator. J Nat Prod 2005; 68 (3): 374-80 (Pubitemid 40545474)
54. Abdel-Salam OME. Drugs used to treat Parkinson's disease, present status and future directions. CNS Neurol Disord Drug Targets 2008; 7 (4): 321-42
55. Radad K, Gille G, Moldzio R, et al. Ginsenosides Rb1 and Rg1 effects on mesencephalic dopaminergic cells stressed with glutamate. Brain Res 2004; 1021 (1): 41-53 (Pubitemid 39158655)
56. Houghton PJ, Howes MJ. Natural products and derivatives affecting neurotransmission relevant to Alzheimer's and Parkinson's disease. Neurosignals 2005; 14 (1-2): 6-22 (Pubitemid 40868980)
57. Urbain A, Marston A, Grilo LS, et al. Xanthones from Gentianella amarella ssp. acuta with acetylcholinesterase and monoamine oxidase inhibitory activities. J Nat Prod 2008; 71 (5): 895-7 (Pubitemid 351841446)
58. Mao Q-Q, Zhong X-M, Feng C-R, et al. Protective effects of paeoniflorin against glutamate-induced neurotoxicity in PC12 cells via antioxidant mechanisms and Ca2+ antagonism. Cell Mol Neurobiol 2010; 30 (7): 1059-66
59. Matteucci A, Cammarota R, Paradisi S, et al. Curcumin protects against NMDA-induced toxicity: a possible role for NR2A subunit. Invest Ophthalmol Vis Sci 2011; 52 (2): 1070-7
60. Kang TH, Murakami Y, Takayama H, et al. Protective effect of rhynchophylline and isorhynchophylline on in vitro ischemia-induced neuronal damage in the hippocampus: putative neurotransmitter receptors involved in their action. Life Sci 2004; 76 (3): 331-43 (Pubitemid 39452914)
61. Lee E, Kim S, Chung KC, et al. 20(S)-ginsenoside Rh2, a newly identified active ingredient of ginseng, inhibits NMDA receptors in cultured rat hippocampal neurons. Eur J Pharmacol 2006; 536 (1-2): 69-77
62. Kim S, Kim T, Ahn K, et al. Ginsenoside Rg3 antagonizes NMDAreceptors through a glycine modulatory site in rat cultured hippocampal neurons. Biochem Biophys Res Commun 2004; 323 (2): 416-24 (Pubitemid 39221114)
63. Ho YS, Yu MS, Yik SY, et al. Polysaccharides from wolfberry antagonizes glutamate excitotoxicity in rat cortical neurons. Cell Mol Neurobiol 2009; 29 (8): 1233-44
64. Hong EJ, Jung EM, Lee GS, et al. Protective effects of the pyrolyzates derived from bamboo against neuronal damage and hematoaggregation. J Ethnopharmacol 2010; 128 (3): 594-9
65. Nakajima A, Yamakuni T, Matsuzaki K, et al. Nobiletin, a citrus flavonoid, reverses learning impairment associated with N-methyl-D-aspartate receptor antagonism by activation of extracellular signal-regulated kinase signaling. J Pharmacol Exp Ther 2007; 321 (2): 784-90 (Pubitemid 46624523)
66. Galindo MF, Ikuta I, Zhu X, et al. Mitochondrial biology in Alzheimer's disease pathogenesis. J Neurochem 2010; 114 (4): 933-45
67. Moreira PI, Santos MS, Oliveira CR, et al. Alzheimer disease and the role of free radicals in the pathogenesis of the disease. CNS Neurol Disord Drug Targets 2008; 7 (1): 3-10 (Pubitemid 351516211)
68. Liu Q, Xie F, Rolston R, et al. Prevention and treatment of Alzheimer disease and aging: antioxidants.Mini RevMed Chem 2007; 7 (2): 171-80 (Pubitemid 46592180)
69. Kim J, Lee HJ, Lee KW. Naturally occurring phytochemicals for the prevention of Alzheimer's disease. J Neurochem 2010; 112 (6): 1415-30
70. Liu T, Jin H, Sun QR, et al. The neuroprotective effects of tanshinone IIA on b-amyloid-induced toxicity in rat cortical neurons. Neuropharmacology 2010; 59 (7-8): 595-604
71. Xie X, Wang H-T, Li C-L, et al. Ginsenoside Rb1 protects PC12 cells against b-amyloid-induced cell injury. Mol Med Rep 2010; 3 (4): 635-9
72. Lee JW, Lee YK, Lee BJ, et al. Inhibitory effect of ethanol extract of Magnolia officinalis and 4-O-methylhonokiol on memory impairment and neuronal toxicity induced by b-amyloid. Pharmacol Biochem Behav 2010; 95 (1): 31-40
73. Lu P, Mamiya T, Lu LL, et al. Silibinin prevents amyloid-b peptide-induced memory impairment and oxidative stress in mice. Br J Pharmacol 2009; 157 (7): 1270-7
74. Guzmán-Beltrá S, Espada S, Orozco-Ibarra M, et al. Nordihydroguaiaretic acid activates the antioxidant pathway Nrf2/HO-1 and protects cerebellar granule neurons against oxidative stress. Neurosci Lett 2008;447(2-3): 167-71
75. Lu JM, Nurko J, Weakley SM, et al. Molecular mechanisms and clinical applications of nordihydroguaiaretic acid (NDGA) and its derivatives: an update. Med Sci Monit 2010 16 (5): RA93-100
76. Amor S, Puentes F, Baker D, et al. Inflammation in neurodegenerative diseases. Immunology 2010; 129 (2): 154-69
77. Lee YJ, Han SB, Nam SY, et al. Inflammation and Alzheimer's disease. Arch Pharm Res 2010; 33 (10): 1539-56
78. Shukitt-Hale B, Lau FC, Carey AN, et al. Blueberry polyphenols attenuate kainic acid-induced decrements in cognition and alter inflammatory gene expression in rat hippocampus. Nutr Neurosci 2008; 11 (4): 172-82
79. Lim CS, Jin D-Q, Mok H, et al. Antioxidant and antiinflammatory activities of xanthorrhizol in hippocampal neurons and primary cultured microglia. J Neurosci Res 2005; 82 (6): 831-8 (Pubitemid 41746496)
80. Nam KN, Park Y-M, Jung H-J, et al. Anti-inflammatory effects of crocin and crocetin in rat brain microglial cells. Eur J Pharmacol 2010; 648 (1-3): 110-6
81. Liu M-H, Lin Y-S, Sheu S-Y, et al. Anti-inflammatory effects of daidzein on primary astroglial cell culture. Nutr Neurosci 2009; 12 (3): 123-34
82. Zheng LT, Ock J, Kwon B-M, et al. Suppressive effects of flavonoid fisetin on lipopolysaccharide-induced microglial activation and neurotoxicity. Int Immunopharmacol 2008; 8 (3): 484-94
83. Allison AC, Cacabelos R, Lombardi VRM, et al. Celastrol, a potent antioxidant and anti-inflammatory drug, as a possible treatment for Alzheimer's disease. Prog Neuropsychopharmacol Biol Psychiatry 2001; 25 (7): 1341-57 (Pubitemid 33022713)
84. Shankar GM, Walsh DM. Alzheimer's disease: synaptic dysfunction and Ab. Mol Neurodegener 2009; 4: 48
85. Teter B, Ashford JW. Neuroplasticity in Alzheimer's disease. J Neurosci Res 2002; 70 (3): 402-37 (Pubitemid 35222379)
86. Tohda C, Kuboyama T, Komatsu K. Search for natural products related to regeneration of the neuronal network. Neurosignals 2005; 14 (1-2): 34-45 (Pubitemid 40868982)
87. Kuboyama T, Tohda C, Komatsu K. Withanoside IV and its active metabolite, sominone, attenuate Ab(25-35)- induced neurodegeneration. Eur J Neurosci 2006; 23 (6): 1417-26
88. Chiba K, Yamazaki M, Kikuchi M, et al. New physiological function of secoiridoids: neuritogenic activity in PC12h cells. J Nat Med 2011; 65 (1): 186-90
89. Karima O, Riazi G, Yousefi R, et al. The enhancement effect of b-boswellic acid on hippocampal neurites outgrowth and branching (an in vitro study). Neurol Sci 2010; 31 (3): 315-20
90. KuboM, Kishimoto Y, HaradaK, et al. NGF-potentiating vibsane-type diterpenoids from Viburnum sieboldii. Bioorg Med Chem Lett 2010; 20 (8): 2566-71
91. Lazarov O, Marr RA. Neurogenesis and Alzheimer's disease: at the crossroads. Exp Neurol 2010; 223 (2): 267-81
92. Gundimeda U, McNeill TH, Schiffman JE, et al. Green tea polyphenols potentiate the action of nerve growth factor to induce neuritogenesis: possible role of reactive oxygen species. J Neurosci Res 2010; 88 (16): 3644-55
93. Lim JS, Yoo M, Kwon HJ, et al. Wogonin induces differentiation and neurite outgrowth of neural precursor cells. Biochem Biophys Res Commun 2010; 402 (1): 42-7
94. Gao L, Xiang L, Luo Y, et al. Gentisides C-K: nine new neuritogenic compounds from the traditional Chinese medicine Gentiana rigescens Franch. Bioorg Med Chem 2010; 18 (19): 6995-7000
95. Kosaka K, Mimura J, Itoh K, et al. Role of Nrf2 and p62/ZIP in the neurite outgrowth by carnosic acid in PC12h cells. J Biochem 2010; 147 (1): 73-81
96. Rudakewich M, Ba F, Benishin CG. Neurotrophic and neuroprotective actions of ginsenosides Rb1 and Rg1. Planta Med 2001; 67 (6): 533-7 (Pubitemid 32800419)
97. Jia WL, Song JT, De Barry J, et al. Panaxadiol glycosides that induce neuronal differentiation in neurosphere stem cells. J Nat Prod 2007; 70 (8): 1329-34 (Pubitemid 47401575)
98. Tchantchou F, Lacor PN, Cao Z, et al. Stimulation of neurogenesis and synaptogenesis by bilobalide and quercetin via common final pathway in hippocampal neurons. J Alzheimers Dis 2009; 18 (4): 787-98
99. de Toledo Ferraz Alves TC, Ferreira LK, Wajngarten M, et al. Cardiac disorders as risk factors for Alzheimer's disease. J Alzheimers Dis 2010; 20 (3): 749-63
100. Zhou J, Zhou S. Antihypertensive and neuroprotective activities of rhynchophylline: the role of rhynchophylline in neurotransmission and ion channel activity. J Ethnopharmacol 2010; 132 (1): 15-27
101. Cui HS, Matsumoto K, Murakami Y, et al. Berberine exerts neuroprotective actions against in vitro ischemiainduced neuronal cell damage in organotypic hippocampal slice cultures: involvement of B-cell lymphoma 2 phosphorylation suppression. Biol Pharm Bull 2009; 32 (1): 79-85
102. Carmeli E, Harpaz Y, Kogan NN, et al. The effect of an endogenous antioxidant glabridin on oxidized LDL. J Basic Clin Physiol Pharmacol 2008; 19 (1): 49-63
103. Lee KT, Sohn IC, Kim DH, et al. Hypoglycemic and hypolipidemic effects of tectorigenin and kaikasaponin III in the streptozotocin-induced diabetic rat and their antioxidant activity in vitro. Arch Pharm Res 2000; 23 (5): 461-6
104. Takagi S, Miura T, Ishihara E, et al. Effect of corosolic acid on dietary hypercholesterolemia and hepatic steatosis in KK-Ay diabetic mice. Biomed Res 2010; 31 (4): 213-8
105. Imenshahidi M, Hosseinzadeh H, Javadpour Y. Hypotensive effect of aqueous saffron extract (Crocus sativus L.) and its constituents, safranal and crocin, in normotensive and hypertensive rats. Phytother Res 2010; 24 (7): 990-4
106. Sims-Robinson C, Kim B, Rosko A, et al. How does diabetes accelerate Alzheimer disease pathology? Nat Rev Neurol 2010; 6 (10): 551-9
107. Zhou JY, Zhou SW, Tang JL, et al. Protective effect of berberine on beta cells in streptozotocin- and high-carbohydrate/high-fat diet-induced diabetic rats. Eur J Pharmacol 2009; 66 (1-3): 262-8
108. Kubo H, Inoue M, Kamei J, et al. Hypoglycemic effects of multiflorine derivatives in normal mice. Biol Pharm Bull 2006; 29 (10): 2046-50 (Pubitemid 44510807)
109. Won H-S, Lee J, Khil L-Y, et al. Mechanism of action of brazilin on gluconeogenesis in isolated rat hepatocytes. Planta Med 2004; 70 (8): 740-4 (Pubitemid 39178935)
110. Bajpai MB, Asthana RK, Sharma NK, et al. Hypoglycemic effect of swerchirin from the hexane fraction of Swertia chirayita. Planta Med 1991; 57 (2): 102-4
111. Chen T-H, Chen S-C, Chan P, et al. Mechanism of the hypoglycemic effect of stevioside, a glycoside of Stevia rebaudiana. Planta Med 2005; 71 (2): 108-13 (Pubitemid 40363551)
112. Xi L, Qian Z, Xu G, et al. Beneficial impact of crocetin, a carotenoid from saffron, on insulin sensitivity in fructosefed rats. J Nutr Biochem 2007; 18 (1): 64-72 (Pubitemid 44827721)
113. Muñoz-Torrero D. Acetylcholinesterase inhibitors as disease- modifying therapies for Alzheimer's disease. Curr Med Chem 2008; 15 (24): 2433-55
114. Ballard CG, Chalmers KA, Todd C, et al. Cholinesterase inhibitors reduce cortical Ab in dementia with Lewy bodies. Neurology 2007; 68 (20): 1726-9 (Pubitemid 46763261)
115. Muth K, Schönmeyer R, Matura S, et al. Mild cognitive impairment in the elderly is associated with volume loss of the cholinergic basal forebrain region. Biol Psychiatry 2010; 67 (6): 588-91
116. Kendziorra K, Wolf H, Meyer PM, et al. Decreased cerebral a4b2*nicotinic acetylcholine receptor availability in patients with mild cognitive impairment and Alzheimer's disease assessed with positron emission tomography. Eur J Nucl Med Mol Imaging 2011; 38 (3): 515-25
117. Diniz BS, Pinto Jr JA, Gonzaga ML, et al. To treat or not to treat? A meta-analysis of the use of cholinesterase inhibitors in mild cognitive impairment for delaying progression to Alzheimer's disease. Eur Arch Psychiatry Clin Neurosci 2009; 259 (4): 248-56
118. Ballard CG, Gauthier S, Cummings JL, et al. Management of agitation and aggression associated with Alzheimer disease. Nat Rev Neurol 2009; 5 (5): 245-55
119. Starkstein SE, Mizrahi R, Power BD. Depression in Alzheimer's disease: phenomenology, clinical correlates and treatment. Int Rev Psychiatry 2008; 20 (4): 382-8
120. Bains J, Birks JS, Dening TR. The efficacy of antidepressants in the treatment of depression in dementia. Cochrane Database Syst Rev 2002; 4: CD003944
121. Panza F, Capurso C, D?Introno A, et al. Mediterranean diet, mild cognitive impairment, and Alzheimer's disease. Exp Gerontol 2007; 42 (1-2): 6-7 (Pubitemid 44937833)
122. McGuinness B, Craig D, Bullock R, et al. Statins for the prevention of dementia. Cochrane Database Syst Rev 2009; 2: CD003160
123. Szekely CA, Zandi PP. Non-steroidal anti-inflammatory drugs and Alzheimer's disease: the epidemiological evidence. CNS Neurol Disord Drug Targets 2010; 9 (2): 132-9
124. O?Brien JT, Burns A. Clinical practice with anti-dementia drugs: a revised (second) consensus statement from the British Association for Psychopharmacology. J Psychopharmacol. Epub 2010 Nov 18
125. Li NC, Lee A, Whitmer RA, et al. Use of angiotensin receptor blockers and risk of dementia in a predominantly male population: prospective cohort analysis. BMJ 2010; 340: b5465
126. Spencer JP. The impact of fruit flavonoids on memory and cognition. Br J Nutr 2010; 104 Suppl. 3: S40-7
127. Nicholson CD. Pharmacology of nootropics and metabolically active compounds in relation to their use in dementia. Psychopharmacology 1990; 101 (2): 147-59 (Pubitemid 20140211)
128. de Mendonc?a A, Cunha RA. Putative neuroprotective effects of caffeine in clinical trials: concluding remarks. J Alzheimers Dis 2010; 20 Suppl. 1: S249-52
129. Houghton PJ, Ren YH, Howes MJ. Acetylcholinesterase inhibitors from plants and fungi. Nat Prod Rep 2006; 23 (2): 181-99
130. Ellis JR, Nathan PJ, Villemagne VL, et al. Galantamineinduced improvements in cognitive function are not related to alterations in a4b2 nicotinic receptors in early Alzheimer's disease as measured in vivo by 2-[18F]fluoro- A-85380 PET. Psychopharmacology 2009; 202 (1-3): 79-91
131. Penner J, Rupsingh R, Smith M, et al. Increased glutamate in the hippocampus after galantamine treatment for Alzheimer disease. Prog Neuropsychopharmacol Biol Psychiatry 2010; 34 (1): 104-10
132. Li Q, Fang J, Yang M, et al. Galantamine inhibits calpaincalcineurin signaling activated by b-amyloid in human neuroblastoma SH-SY5Y cells. Neurosci Lett 2010; 480 (3): 173-7
133. Li Q, Wu D, Zhang L, et al. Effects of galantamine on b-amyloid release and b-site cleaving enzyme 1 expression in differentiated human neuroblastoma SH-SY5Y cells. Exp Gerontol 2010; 45 (11): 842-7
134. Matharu B, Gibson G, Parsons R, et al. Galantamine inhibits b-amyloid aggregation and cytotoxicity. J Neurol Sci 2009; 280 (1-2): 49-58
135. Melo JB, Sousa C, Garc?a?o P, et al. Galantamine protects against oxidative stress induced by amyloid-b peptide in cortical neurons. Eur J Neurosci 2009; 29 (3): 455-64
136. Birks J. Cholinesterase inhibitors for Alzheimer's disease. Cochrane Database Syst Rev 2006; 1: CD005593
137. Rodda J, Morgan S, Walker Z. Are cholinesterase inhibitors effective in the management of the behavioral and psychological symptoms of dementia in Alzheimer's disease? A systematic review of randomized, placebo- controlled trials of donepezil, rivastigmine and galantamine. Int Psychogeriatr 2009; 21 (5): 813-24
138. Small G, Erkinjuntti T, Kurz A, et al. Galantamine in the treatment of cognitive decline in patients with vascular dementia or Alzheimer's disease with cerebrovascular disease. CNS Drugs 2003; 17 (12): 905-14 (Pubitemid 37211113)
139. Edwards K, Royall D, Hershey L, et al. Efficacy and safety of galantamine in patients with dementia with Lewy bodies: a 24-week open-label study. Dement Geriatr Cogn Disord 2007; 23 (6): 401-5 (Pubitemid 46897177)
140. Litvinenko IV, Odinak MM, Mogil?naya VI, et al. Efficacy and safety of galantamine (Reminyl) for dementia in patients with Parkinson's disease (an open controlled trial). Neurosci Behav Physiol 2008; 38 (9): 937-45
141. Loy C, Schneider L. Galantamine for Alzheimer's disease and mild cognitive impairment. Cochrane Database Syst Rev 2006; 25: CD001747
142. Tangwongchai S, Thavichachart N, Senanarong V, et al. Galantamine for the treatment of BPSD in Thai patients with possible Alzheimer's disease with or without cerebrovascular disease. Am J Alzheimers Dis Other Demen 2009; 23 (6): 593-601
143. Lockhart IA, Mitchell SA, Kelly S. Safety and tolerability of donepezil, rivastigmine and galantamine for patients with Alzheimer's disease: systematic review of the ?realworld? evidence. Dement Geriatr Cogn Disord 2009; 28 (5): 389-403
144. Leonard AK, Sileno AP, Macevilly C, et al. Development of a novel high-concentration galantamine formulation suitable for intranasal delivery. J Pharm Sci 2005; 94 (8): 1736-46 (Pubitemid 41360868)
145. Maelicke A, Hoeffle-Maas A, Ludwig J, et al. Memogain is a galantamine pro-drug having dramatically reduced adverse effects and enhanced efficacy. JMol Neurosci 2010; 40 (1-2): 135-7
146. Loizzo MR, Tundis R, Menichini F, et al. Natural products and their derivatives as cholinesterase inhibitors in the treatment of neurodegenerative disorders: an update. Curr Med Chem 2008; 15 (12): 1209-28 (Pubitemid 351997808)
147. Jin Z. Amaryllidaceae and Sceletium alkaloids. Nat Prod Rep 2009; 26 (3): 363-81
148. McNulty J, Nair JJ, Little JRL, et al. Structure-activity studies on acetylcholinesterase inhibition in the lycorine series of Amaryllidaceae alkaloids. Bioorg Med Chem Lett 2010; 20 (17): 5290-4
149. Yoshida S, Suzuki N. Antiamnesic and cholinomimetic side-effects of the cholinesterase inhibitors, physostigmine, tacrine and NIK-247 in rats. Eur J Pharmacol 1993; 250 (1): 117-24 (Pubitemid 23353067)
150. Thal LJ, Ferguson JM, Mintzer J, et al. A 24-week randomized trial of controlled release physostigmine in patients with Alzheimer's disease. Neurology 1999; 52 (6): 1146-52 (Pubitemid 29177913)
151. Coelho F, Birks J. Physostigmine for Alzheimer's disease. Cochrane Database Syst Rev 2001; 2: CD001499
152. Braida D, Sala M. Eptastigmine: ten years of pharmacology, toxicology, pharmacokinetic, and clinical studies. CNS Drug Rev 2001; 7 (4): 369-86 (Pubitemid 34263872)
153. Kamal MA, Al-Jafari AA, Yu QS, et al. Kinetic analysis of the inhibition of human butyrylcholinesterase with cymserine. Biochim Biophys Acta 2006; 1760 (2): 200-6 (Pubitemid 43320508)
154. Kamal MA, Klein P, Yu QS, et al. Kinetics of human serum butyrylcholinesterase and its inhibition by a novel experimental Alzheimer therapeutic, bisnorcymserine. J Alzheimers Dis 2006; 10 (1): 43-51 (Pubitemid 44401365)
155. KamalMA, Qu X, Yu Q-S, et al. Tetrahydrofurobenzofuran cymserine, a potent butyrylcholinesterase inhibitor and experimental Alzheimer drug candidate, enzyme kinetic analysis. J Neural Transm 2008; 115 (6): 889-98
156. Butler MS. Natural products to drugs: natural productderived compounds in clinical trials. Nat Prod Rep 2008; 25 (3): 475-516 (Pubitemid 351725315)
157. Fink DM, Palermo MG, Bores GM, et al. Imino 1, 2, 3, 4- tetrahydrocyclopent[b]indole carbamates as dual inhibitors of acetylcholinesterase and monoamine oxidase. Bioorg Med Chem Lett 1996; 6 (6): 625-30 (Pubitemid 26107892)
158. Toda N, Kaneko T, Kogen H. Development of an efficient therapeutic agent for Alzheimer's disease: design and synthesis of dual inhibitors of acetylcholinesterase and serotonin transporter. Chem Pharm Bull 2010; 58 (3): 273-87
159. Ma X, Tan C, Zhu D, et al. Huperzine A from Huperzia species: an ethnopharmacolgical review. J Ethnopharmacol 2007; 113 (1): 15-34 (Pubitemid 47077860)
160. He X-C, Feng S, Wang Z-F, et al. Study on dual-site inhibitors of acetylcholinesterase: highly potent derivatives of bis- and bifunctional huperzine B. Bioorg Med Chem 2007; 15 (3): 1394-408 (Pubitemid 46049824)
161. Tang LL, Wang R, Tang XC. Effects of huperzine A on secretion of nerve growth factor in cultured rat cortical astrocytes and neurite outgrowth in rat PC12 cells. Acta Pharmacol Sin 2005; 26 (6): 673-8 (Pubitemid 40806555)
162. Wang R, YanH, Tang XC. Progress in studies of huperzine A, a natural cholinesterase inhibitor from Chinese herbal medicine. Acta Pharmacol Sin 2006; 27 (1): 1-26 (Pubitemid 43051942)
163. Wang BS, Wang H, Wei ZH, et al. Efficacy and safety of natural acetylcholinesterase inhibitor huperzine A in the treatment of Alzheimer's disease: an updated meta-analysis. J Neural Transm 2009; 116 (4): 457-65
164. Hao Z, Liu M, Liu Z, et al. Huperzine A for vascular dementia. Cochrane Database Syst Rev 2009; 2: CD007365
165. Ronco C, Sorin G, Nachon F, et al. Synthesis and structure- activity relationship of huprine derivatives as human acetylcholinesterase inhibitors. Bioorg Med Chem 2009; 17 (13): 4523-36
166. Camps P, Cusack B, Mallender WD, et al. Huprine X is a novel high-affinity inhibitor of acetylcholinesterase that is of interest for treatment of Alzheimer's disease. Mol Pharmacol 2000; 57 (2): 409-17 (Pubitemid 30084519)
167. Merlini L, Pinza M. Trends in searching for new cognition enhancing drugs. Prog Neuropsychopharmacol Biol Psychiatry 1989; 13 (Suppl.): S61-75 (Pubitemid 20073494)
168. Deshmukh R, Sharma V, Mehan S, et al. Amelioration of intracerebroventricular streptozotocin induced cognitive dysfunction and oxidative stress by vinpocetine: a PDE1 inhibitor. Eur J Pharmacol 2009; 620 (1-3): 49-56
169. ErdõSL, Molnár P, Lakics P, et al. Vincamine and vincanol are potent blockers of voltage-gated Na+ channels. Eur J Pharmacol 1996; 314 (1-2): 69-73 (Pubitemid 26378887)
170. Nyakas C, Felszeghy K, SzaböR, et al. Neuroprotective effects of vinpocetine and its major metabolite cis-apovincaminic acid on NMDA-induced neurotoxicity in a rat entorhinal cortex lesion model. CNS Neurosci Ther 2009; 15 (2): 89-99
171. Akhondzadeh S, Abbasi SH. Herbal medicine in the treatment of Alzheimer's disease. Am J Alzheimers Dis Other Demen 2006; 21 (2): 113-8
172. Valikovics A. Investigation of the effect of vinpocetine on cerebral blood flow and cognitive functions. Ideggyogy Sz 2007; 60 (7-8): 301-10
173. Szatmari SZ, Whitehouse PJ. Vinpocetine for cognitive impairment and dementia. Cochrane Database Syst Rev 2003; 1: CD003119
174. Khanavi M, Pourmoslemi S, Farahanikia B, et al. Cytotoxicity of Vinca minor. Pharm Biol 2010; 48 (1): 96-100
175. Howes M-JR, Houghton PJ. Traditional medicine for memory enhancement. In: Ramawat KG, editor. Herbal drugs: ethnomedicine to modern medicine. New York: Springer, 2009: 239-91
176. Elbaz A, Moisan F. Update in the epidemiology of Parkinson's disease. Curr Opin Neurol 2008; 21 (4): 454-60
177. Dome P, Lazary J, Kalapos MP, et al. Smoking, nicotine and neuropsychiatric disorders. Neurosci Biobehav Rev 2010; 34 (3): 295-342
178. Levin ED, Christopher CN. Lobeline-induced learning improvement of rats in the radial-arm maze. Pharmacol Biochem Behav 2003; 76 (1): 133-9 (Pubitemid 38366176)
179. Romero J, Martinez Orgado J. Cannabinoids and neurodegenerative diseases. CNS Neurol Disord Drug Targets 2009; 8 (6): 440-50
180. Esposito G, De Filippis D, Carnuccio R, et al. The marijuana component cannabidiol inhibits b-amyloidinduced tau protein hyperphosphorylation through Wnt/b-catenin pathway rescue in PC12 cells. J Mol Med 2006; 84 (3): 253-8 (Pubitemid 43291014)
181. Janero DR, Vadivel SK, Makriyannis A. Pharmacotherapeutic modulation of the endocannabinoid signalling system in psychiatric disorders: drug-discovery strategies. Int Rev Psychiatry 2009; 21 (2): 122-33
182. Orgado JM, Fernádez-Ruiz J, Romero J. The endocannabinoid system in neuropathological states. Int Rev Psychiatry 2009; 21 (2): 172-80
183. Walther S, Mahlberg R, Eichmann U, et al. D-9-Tetrahydrocannabinol for nighttime agitation in severe dementia. Psychopharmacology 2006; 185 (4): 524-8
184. Zuardi AW, Crippa JA, Hallak JE, et al. Cannabidiol, a Cannabis sativa constituent, as an antipsychotic drug. Braz J Med Biol Res 2006; 39 (4): 421-9
185. Zuardi AW, Crippa JA, Hallak JE, et al. Cannabidiol for the treatment of psychosis in Parkinson's disease. J Psychopharmacol 2009; 23 (8): 979-83
186. Krishnan S, Cairns R, Howard R. Cannabinoids for the treatment of dementia. Cochrane Database Syst Rev 2009; 2: CD007204
187. Ng T-P, Chiam P-C, Lee T, et al. Curry consumption and cognitive function in the elderly. Am J Epidemiol 2006; 164 (9): 898-906 (Pubitemid 44627275)
188. Kim DS, Kim JY. Total synthesis of calebin A, preparation of its analogues, and their neuronal cell protectivity against b-amyloid insult. Bioorg MedChem Lett 2001; 11 (18): 2541-3 (Pubitemid 32823351)
189. Park SY, Kim DS. Discovery of natural products from Curcuma longa that protect cells from b-amyloid insult: a drug discovery effort against Alzheimer's disease. J Nat Prod 2002; 65 (9): 1227-31
190. 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 (4): 367-77 (Pubitemid 39287248)
191. Pal R, Cristan EA, Schnittker K, et al. Rescue of ER oxidoreductase function through polyphenolic phytochemical intervention: implications for subcellular traffic and neurodegenerative disorders. Biochem Biophys Res Commun 2010; 392 (4): 567-71
192. Agrawal R, Mishra B, Tyagi E, et al. Effect of curcumin on brain insulin receptors and memory functions in STZ (ICV) induced dementia model of rat. Pharmacol Res 2010; 61 (3): 247-52
193. Awasthi H, Tota S, Hanif K, et al. Protective effect of curcumin against intracerebral streptozotocin induced impairment in memory and cerebral blood flow. Life Sci 2010; 86 (3-4): 87-94
194. Kumar A, Dogra S, Prakash A. Protective effect of curcumin (Curcuma longa), against aluminium toxicity: possible behavioral and biochemical alterations in rats. Behav Brain Res 2009; 205 (2): 384-90
195. Yaari R, Kumar S, Tariot PN. Non-cholinergic drug development for Alzheimer's disease. Expert Opin Drug Discov 2008; 3 (7): 745-60
196. Narlawar R, Baumann K, Schubenel R, et al. Curcumin derivatives inhibit or modulate b-amyloid precursor protein metabolism. Neurodegener Dis 2007; 4 (2-3): 88-93 (Pubitemid 47000401)
197. Maher P, Akaishi T, Schubert D, et al. A pyrazole derivative of curcumin enhances memory. Neurobiol Aging 2010; 31 (4): 706-9
198. Baum L, Lam CW, Cheung SK, et al. Six-month randomized, placebo-controlled, double-blind, pilot clinical trial of curcumin in patients with Alzheimer disease. J Clin Psychopharmacol 2008; 28 (1): 110-3
199. Collins MA, Neafsey EJ, Mukamal KJ, et al. Alcohol in moderation, cardioprotection, and neuroprotection: epidemiological considerations and mechanistic studies. Alcohol Clin Exp Res 2009; 33 (2): 206-19
200. Solfrizzi V, D?Introno A, Colacicco AM, et al. Alcohol consumption, mild cognitive impairment, and progression to dementia. Neurology 2007; 68 (21): 1790-9 (Pubitemid 46791391)
201. Mehlig K, Skoog I, Guo X, et al. Alcoholic beverages and incidence of dementia: 34-Year follow-up of the prospective population study of women in Göteborg. Am J Epidemiol 2008; 167 (6): 684-91 (Pubitemid 351430938)
202. Rocha-González HI, Ambriz-Tututi M, Granados-Soto V. Resveratrol: a natural compound with pharmacological potential in neurodegenerative diseases. CNS Neurosci Ther 2008;14(3) 234-47
203. Panza F, Capurso C, D?Introno A, et al. Alcohol drinking, cognitive functions in older age, predementia, and dementia syndromes. J Alzheimers Dis 2009; 17 (1): 7-31
204. Jang JH, Surh YJ. Protective effect of resveratrol on b-amyloid-induced oxidative PC12 cell death. Free Radic Biol Med 2003; 34 (8): 1100-10
205. Rossi M, Caruso F, Opazo C, et al. Crystal and molecular structure of piceatannol; scavenging features of resveratrol and piceatannol on hydroxyl and peroxyl radicals and docking with transthyretin. J Agric Food Chem 2008; 56 (22): 10557-66
206. Vingtdeux V, Dreses-Werringloer U, Zhao H, et al. Therapeutic potential of resveratrol in Alzheimer's disease. BMC Neurosci 2008; 9 Suppl. 2: S6
207. Pallàs M, Casadesu's G, Smith MA, et al. Resveratrol and neurodegenerative diseases: activation of SIRT1 as the potential pathway towards neuroprotection. Curr Neurovasc Res 2009; 6 (1): 70-81
208. Kumar A, Naidu PS, Seghal N, et al. Neuroprotective effects of resveratrol against intracerebroventricular colchicine- induced cognitive impairment and oxidative stress in rats. Pharmacology 2007; 79 (1): 17-26 (Pubitemid 46034173)
209. Karuppagounder SS, Pinto JT, Xu H, et al. Dietary supplementation with resveratrol reduces plaque pathology in a transgenic model of Alzheimer's disease. Neurochem Int 2008; 54 (2): 111-8
210. Gertz H-J, Kiefer M. Review about Ginkgo biloba special extract EGb 761 (Ginkgo). Curr Pharm Des 2004; 10 (3): 261-4 (Pubitemid 38072762)
211. Chan P-C, Xia Q, Fu PP. Ginkgo biloba leaf extract: biological, medicinal, and toxicological effects. J Environ Sci Health C Environ Carcinog Ecotoxicol Rev 2007; 25 (3): 211-44 (Pubitemid 47347114)
212. Das A, Shanker G, Nath C, et al. A comparative study in rodents of standardized extracts of Bacopa monniera and Ginkgo biloba: anticholinesterase and cognitive enhancing activities. Pharmcol Biochem Behav 2002; 73 (4): 893-900 (Pubitemid 35246239)
213. Birks J, Grimley EV, Van Dongen M. Ginkgo biloba for cognitive impairment and dementia. Cochrane Database Syst Rev 2002; 4: CD003120
214. Birks J, Grimley Evans J. Ginkgo biloba for cognitive impairment and dementia. Cochrane Database Syst Rev 2007; 2: CD003120
215. Birks J, Grimley Evans J. Ginkgo biloba for cognitive impairment and dementia. Cochrane Database Syst Rev 2009; 1: CD003120
216. Kaschel R. Ginkgo biloba: specificity of neuropsychological improvement - a selective review in search of differential effects. Hum Psychopharmaol 2009; 24 (5): 345-70
217. Weinmann S, Roll S, Schwarzbach C, et al. Effects of Ginkgo biloba in dementia: systematic review and metaanalysis. BMC Geriatr 2010; 10: 14
218. DeKosky ST, Williamson JD, Fitzpatrick AL, et al. Ginkgo biloba for prevention of dementia: a randomized controlled trial [published erratum appears in JAMA 2008; 300 (23): 2730]. JAMA 2008; 300 (19): 2253-62
219. Andrieu S, Ousset P-J, Coley N, et al. GuidAge study: a 5-year double blind, randomised trial of EGb 761 for the prevention of Alzheimer's disease in elderly subjects with memory complaints, I: rationale, design and baseline data. Curr Alzheimer Res 2008; 5 (4): 406-15
220. Yancheva S, Ihl R, Nikolova G, et al. Ginkgo biloba extract EGb 761 donepezil or both combined in the treatment of Alzheimer's disease with neuropsychiatric features: a randomised, double-blind, exploratory trial. Aging Ment Health 2009; 13 (2): 183-90
221. Yasui-Furukori N, Furukori H, Kaneda A, et al. The effects of Ginkgo biloba extracts on the pharmacokinetics and pharmacodynamics of donepezil. J Clin Pharmacol 2004; 44 (5): 538-42 (Pubitemid 38509723)
222. Barnes J, Anderson LA, Phillipson JD. Herbal medicines. 3rd ed. London: Pharmaceutical Press, 2007
223. Scripnikov A, Khomenko A, Napryeyenko O. Effects of Ginkgo biloba extract EGb 761 on neuropsychiatric symptoms of dementia: findings from a randomised controlled trial. Wien Med Wochenschr 2007; 157 (13-14): 295-300 (Pubitemid 47356252)
224. Leistner E, Drewke C. Ginkgo biloba and ginkgotoxin. J Nat Prod 2010; 73 (1): 86-92
225. Bate C, TayebiM, Williams A. Ginkgolides protect against amyloid-b. Mol Neurodegener 2008 Jan 7; 3: 1
226. Shi C, Wu F, Yew DT, et al. Bilobalide prevents apoptosis through activation of the PI3K/Akt pathway in SH-SY5Y cells. Apoptosis 2010; 15 (6): 715-27
227. Ho Y-S, So K-F, Chang RC-C. Anti-aging herbal medicine: how and why can they be used in aging-associated neurodegenerative diseases? Ageing Res Rev 2010; 9 (3): 354-62
228. Radad K, Gille G, Liu L, et al. Use of ginseng in medicine with emphasis on neurodegenerative disorders. J Pharmacol Sci 2006; 100 (3): 175-86
229. Nah S-Y, Kim D-H, Rhim H. Ginsenosides: are any of them candidates for drugs acting on the central nervous system? CNS Drug Rev 2007; 13 (4): 381-404 (Pubitemid 350233470)
230. Lee B, Park J, Kwon S, et al. Effect of wild ginseng on scopolamine-induced acetylcholine depletion in the rat hippocampus. J Pharm Pharmacol 2010; 62 (2): 263-71
231. Kennedy DO, Haskell CF, Wesnes KA, et al. Improved cognitive performance in human volunteers following administration of guarana (Paullinia cupana) extract: comparison and interaction with Panax ginseng. Pharmacol Biochem Behav 2004; 79 (3): 401-11 (Pubitemid 39576158)
232. Heo JH, Lee ST, Chu K, et al. An open-label trial of Korean red ginseng as an adjuvant treatment for cognitive impairment in patients with Alzheimer's disease. Eur J Neurol 2008; 15 (8): 865-8
233. Lee ST, Chu K, Sim JY, et al. Panax ginseng enhances cognitive performance in Alzheimer disease. Alzheimer Dis Assoc Disord 2008; 22 (3): 222-6
234. Tian JZ, Zhu AH, Zhong J. A follow-up study on a randomized, single-blind control of King's Brain pills in treatment of memory disorder in elderly people with MCI in a Beijing community. Zhongguo Zhong Yao Za Zhi 2003; 28 (10): 987-91
235. Lee MS, Yang EJ, Kim JI, et al. Ginseng for cognitive function in Alzheimer's disease: a systematic review. J Alzheimers Dis 2009; 18 (2): 339-41
236. Howes M-JR, Houghton PJ. Plants used in Chinese and Indian traditional medicine for improvement of memory and cognitive function. Pharmacol Biochem Behav 2003; 75 (3): 513-27 (Pubitemid 36939171)
237. Howes M-JR, Perry NSL, Houghton PJ. Plants with traditional uses and activities, relevant to the management of Alzheimer's disease and other cognitive disorders. Phytother Res 2003; 17 (1): 1-18 (Pubitemid 36205453)
238. Chinese Pharmacopoeia Commission. Pharmacopoeia of the People's Republic of China. Beijing: People'sMedical Publishing House, 2005
239. Shin KI, Won BY, Heo C, et al. BT-11 improves stressinduced memory impairments through increment of glucose utilization and total neural cell adhesion molecule levels in rat brains. J Neurosci Res 2009; 87 (1): 260-8
240. Shin KY, Lee J-Y, Won BY, et al. BT-11 is effective for enhancing cognitive functions in the elderly humans. Neurosci Lett 2009; 465 (2): 157-9
241. Lee J-Y, Kim KY, Shin KY, et al. Effects of BT-11 on memory in healthy humans. Neurosci Lett 2009; 454 (2): 111-4
242. Chen Y-J, Huang X-B, Li Z-X, et al. Tenuigenin protects cultured hippocampal neurons against methylglyoxal-induced neurotoxicity. Eur J Pharmacol 2010; 645 (1-3): 1-8
243. Jia H, Jiang Y, Ruan Y, et al. Tenuigenin treatment decreases secretion of the Alzheimer's disease amyloid b-protein in cultured cells. Neurosci Lett 2004; 367 (1): 123-8 (Pubitemid 39078799)
244. Lv J, Jia H, Jiang Y, et al. Tenuifolin, an extract derived from tenuigenin, inhibits amyloid-b secretion in vitro. Acta Physiol 2009; 196 (4): 419-25
245. Lee M-R, Yun B-S, Park S-Y, et al. Anti-amnesic effect of Chong-Myung-Tang on scopolamine-induced memory impairments in mice. J Ethnopharmacol 2010; 132 (1): 70-4
246. Arai H, Suzuki T, Sasaki H, et al. A new interventional strategy for Alzheimer's disease by Japanese herbal medicine. Japanese J Geriatr 2000; 37 (3): 212-5
247. Maruyama M, Tomita N, Iwasaki K, et al. Benefits of combining donepezil plus traditional Japanese herbal medicine on cognition and brain perfusion in Alzheimer's disease: a 12-week observer-blind, donepezil monotherapy controlled trial. J Am Geriatr Soc 2006; 54 (5): 869-71 (Pubitemid 44030226)
248. Wu T, Qingpu L, Zhenyong Y. Yizhi capsule for vascular dementia. Cochrane Database Syst Rev 2009; 2: CD005382
249. Iwasaki K, Kobayashi S, Chimura Y, et al. A randomized, double-blind, placebo-controlled clinical trial of the Chinese herbal medicine ?ba wei di huang wan? in the treatment of dementia. J Am Geriatr Soc 2004; 52 (9): 1518-21 (Pubitemid 39209600)
250. Tong YC, Cheng JT, Wan WC. Effects of ba-wei-diehuang- wan on the cholinergic function and protein expression ofM2 muscarinic receptor of the urinary bladder in diabetic rats. Neurosci Lett 2002; 330 (1): 21-4
251. Park E, Kang M, Oh JW, et al. Yukmijihwang-tang derivatives enhance cognitive processing in normal young adults: a double-blinded, placebo-controlled trial. Am J Chin Med 2005; 33 (1): 107-15 (Pubitemid 40468308)
252. Liu T, Wang CH, Yang J. Modified sanjiasan decoction in regulating intelligence state of patients with vascular dementia. Zhongguo Zhong Xi Yi Jie He Za Zhi 2005; 25 (6): 492-5
253. de Caires S, Steenkamp V. Use of Yokukansan (TJ-54) in the treatment of neurological disorders: a review. Phytother Res 2010; 24 (9): 1265-70
254. Kawakami Z, Kanno H, Ueki T, et al. Neuroprotective effects of yokukansan, a traditional Japanese medicine, on glutamate-mediated excitotoxicity in cultured cells. Neuroscience 2009; 159 (4): 1397-407
255. Tabuchi M, Yamaguchi T, Iizuka S, et al. Ameliorative effects of yokukansan, a traditional Japanese medicine, on learning and non-cognitive disturbances in the Tg2576 mouse model of Alzheimer's disease. J Ethnopharmacol 2009; 122 (1): 157-62
256. Monji AA, Takita MB, Samejima TC, et al. Effect of yokukansan on the behavioral and psychological symptoms of dementia in elderly patients with Alzheimer's disease. Prog Neuro-Psychopharmacol Biol Psychiatry 2009; 33 (2): 308-11
257. Shinno H, Inami Y, Inagaki T, et al. Effect of yi-gan san on psychiatric symptoms and sleep structure at patients with behavioral and psychological symptoms of dementia. Prog Neuro-Psychopharmacol Biol Psychiatry 2008; 32 (3): 881-5 (Pubitemid 351312391)
258. Shinno H, Utani E, Okazaki S, et al. Successful treatment with yi-gan san for psychosis and sleep disturbance in a patient with dementia with Lewy bodies. Prog Neuropsychopharmacol Biol Psychiatry 2007; 31 (7): 1543-5 (Pubitemid 47302569)
259. Hayashi Y, Ishida Y, Inoue T, et al. Treatment of behavioral and psychological symptoms of Alzheimer-type dementia with yokukansan in clinical practice. Prog Neuropsychopharmacol Biol Psychiatry 2010; 34 (3): 541-5
260. Iwasaki K, Satoh-Nakagawa T, Maruyama M, et al. A randomized, observer-blind, controlled trial of the traditional Chinese medicine Yi-Gan San for improvement of behavioral and psychological symptoms and activities of daily living in dementia patients. J Clin Psychiatry 2005; 66 (2): 248-52 (Pubitemid 40314333)
261. Mizukami KA, Asada TA, Kinoshita TB, et al. A randomized cross-over study of a traditional Japanese medicine (kampo), yokukansan, in the treatment of the behavioural and psychological symptoms of dementia. Int J Neuropsychopharmacol 2009; 12 (2): 191-9
262. Okahara K, Ishida Y, Hayashi Y, et al. Effects of yokukansan on behavioral and psychological symptoms of dementia in regular treatment of Alzheimer's disease. Prog Neuropsychopharmacol Biol Psychiatry 2010; 34 (3): 532-6
263. Kimura T, Hayashida H, Furukawa H, et al. Five cases of frontotemporal dementia with behavioral symptoms improved by yokukansan. Psychogeriatrics 2009; 9 (1): 38-43
264. Kawanabe T, Yoritaka A, Shimura H, et al. Successful treatment with yokukansan for behavioral and psychological symptoms of Parkinsonian dementia. Prog Neuro- Psychopharmacol Biol Psychiatry 2010; 34 (2): 284-7
265. Akhondzadeh S, Shafiee Sabet M, Harirchian MH, et al. A 22-week, multicenter, randomized, double-blind controlled trial of Crocus sativus in the treatment of mild-tomoderate Alzheimer's disease. Psychopharmacology 2010; 207 (4): 637-43
266. Akhondzadeh S, Sabet MS, Harirchian MH, et al. Saffron in the treatment of patients with mild to moderate Alzheimer's disease: a 16-week, randomized and placebocontrolled trial. J Clin Pharm Ther 2010; 35 (5): 581-8
267. Ochiai T, Ohno S, Soeda S, et al. Crocin prevents the death of rat pheochromyctoma (PC-12) cells by its antioxidant effects stronger than those of a-tocopherol. Neurosci Lett 2004; 362 (1): 61-4 (Pubitemid 38638385)
268. Soeda S, Ochiai T, Paopong L, et al. Crocin suppresses tumor necrosis factor-a-induced cell death of neuronally differentiated PC-12 cells. Life Sci 2001; 69 (24): 2887-98 (Pubitemid 33030277)
269. Papandreou MA, Kanakis CD, Polissiou MG, et al. Inhibitory activity on amyloid-b aggregation and antioxidant properties of Crocus sativus stigmas extract and its crocin constituents. J Agric Food Chem 2006; 54 (23): 8762-8 (Pubitemid 44797522)
270. Ochiai T, Shimeno H, Mishima K, et al. Protective effects of carotenoids from saffron on neuronal injury in vitro and in vivo. Biochim Biophys Acta 2007; 1770 (4): 578-84 (Pubitemid 46281463)
271. Zheng Y-Q, Liu J-X, Wang J-N, et al. Effects of crocin on reperfusion-induced oxidative/nitrative injury to cerebral microvessels after global cerebral ischemia. Brain Res 2007; 1138 (1): 86-94
272. Ahmad AS, Ansari MA, AhmadM, et al. Neuroprotection by crocetin in a hemi-parkinsonian rat model. Pharmacol Biochem Behav 2005; 81 (4): 805-13 (Pubitemid 41187813)
273. Pitsikas N, Zisopoulou S, Tarantilis PA, et al. Effects of the active constituents of Crocus sativus L., crocins on recognition and spatial rats? memory. Behav Brain Res 2007; 183 (2): 141-6 (Pubitemid 47348125)
274. Ghadami MR, Pourmotabbed A. The effect of crocin on scopolamine induced spatial learning and memory deficits in rats. Physiol Pharmacol 2009; 12 (4): 287-95
275. Hosseinzadeh H, Noraei NB. Anxiolytic and hypnotic effect of Crocus sativus aqueous extract and its constituents, crocin and safranal, in mice. Phytother Res 2009; 23: 768-74
276. Perry NSL, Houghton PJ, Theobald A, et al. In vitro inhibition of human erythrocyte acetylcholinesterase by Salvia lavandulaefolia essential oil and constituent terpenes. J Pharm Pharmacol 2000; 52 (7): 895-902 (Pubitemid 30461925)
277. Savelev S, Okello E, Perry NSL, et al. Synergistic and antagonistic interactions of anticholinesterase terpenoids in Salvia lavandulaefolia essential oil. Pharmacol Biochem Behav 2003; 75 (3): 661-8 (Pubitemid 36936900)
278. Savelev SU, Okello EJ, Perry EK. Butyryl- and acetylcholinesterase inhibitory activities in essential oils of Salvia species and their constituents. Phytother Res 2004; 18 (4): 315-24 (Pubitemid 38619534)
279. Ren YH, Houghton PJ, Hider RC, et al. Novel diterpenoid acetylcholinesterase inhibitors from Salvia miltiorhiza. Planta Med 2004; 70 (3): 201-4 (Pubitemid 38445184)
280. Perry NSL, Houghton PJ, Sampson J, et al. In vitro activities of S. lavandulaefolia (Spanish sage) relevant to treatment of Alzheimer's disease. J Pharm Pharmacol 2001; 53 (10): 1347-56 (Pubitemid 32982251)
281. Iuvone T, De Filippis D, Esposito G, et al. The spice sage and its active ingredient rosmarinic acid protect PC12 cells from amyloid-b peptide-induced neurotoxicity. J Pharmacol Exp Ther 2006; 317 (3): 1143-9 (Pubitemid 43764118)
282. Eidi M, Eidi A, Bahar M. Effects of Salvia officinalis L. (sage) leaves on memory retention and its interaction with the cholinergic system in rats. Nutrition 2006; 22 (3): 321-6 (Pubitemid 43263083)
283. Tildesley NT, Kennedy DO, Perry EK, et al. Salvia lavandulaefolia (Spanish sage) enhances memory in healthy young volunteers. Pharmacol Biochem Behav 2003; 75 (3): 669-74 (Pubitemid 36936901)
284. Tildesley NTJ, Kennedy DO, Perry EK, et al. Positive modulation of mood and cognitive performance following administration of acute doses of Salvia lavandulaefolia essential oil to healthy young volunteers. Physiol Behav 2005; 83 (5): 699-709 (Pubitemid 40091602)
285. Perry NS, Bollen C, Perry EK, et al. Salvia for dementia therapy: review of pharmacological activity and pilot tolerability clinical trial. Pharmacol Biochem Behav 2003; 75 (3): 651-9 (Pubitemid 36936899)
286. Akhondzadeh S, Noroozian M, Mohammadi M, et al. Salvia officinalis extract in the treatment of patients with mild to moderate Alzheimer's disease: a double blind, randomized and placebo-controlled trial. J Clin Pharm Ther 2003; 28 (1): 53-9 (Pubitemid 36313176)
287. Perry N, Court G, Bidet N, et al. European herbs with cholinergic activities: potential in dementia therapy. Int J Geriatr Psychiatry 1996; 11 (12): 1063-9 (Pubitemid 27029813)
288. Wake G, Court J, Pickering A, et al. CNS acetylcholine receptor activity in European medicinal plants traditionally used to improve failing memory. J Ethnopharmacol 2000; 69 (2): 105-14 (Pubitemid 30016025)
289. ElliottMSJ, Abuhamdah S, HowesM-JR, et al. The essential oils from Melissa officinalis L. and Lavandula angustifolia Mill. as potential treatment for agitation in people with severe dementia. Int J Essent Oil Ther 2007; 1 (4): 143-52 (Pubitemid 351250970)
290. Kennedy DO, Scholey AB, Tildesley NTJ, et al. Modulation of mood and cognitive performance following acute administration of Melissa officinalis (lemon balm). Pharmacol Biochem Behav 2002; 72 (4): 953-64 (Pubitemid 34621322)
291. Kennedy DO, Wake G, Savelev S, et al. Modulation of mood and cognitive performance following acute administration of single doses of Melissa officinalis (lemon balm) with human CNS nicotinic and muscarinic receptor- binding properties. Neuropsychopharmacology 2003; 28 (10): 1871-81 (Pubitemid 41070853)
292. Kennedy DO, Little W, Scholey AB. Attenuation of laboratory-induced stress in humans after acute administration of Melissa officinalis (lemon balm). Psychosom Med 2004; 66 (4): 607-13 (Pubitemid 38971258)
293. Akhondzadeh S, Noroozian M, Mohammadi M, et al. Melissa officinalis extract in the treatment of patients with mild to moderate Alzheimer's disease: a double blind, randomised, placebo controlled trial. J Neurol Neurosurg Psychiatry 2003; 74 (7): 863-6 (Pubitemid 36782984)
294. Ballard CG, O?Brien JT, Reichelt K, et al. Aromatherapy as a safe and effective treatment for the management of agitation in severe dementia: the results of a double-blind, placebo-controlled trial with Melissa. J Clin Psychiatry 2002; 63 (7): 553-8 (Pubitemid 34787318)
295. Abuhamdah S, Huang L, Elliott MS, et al. Pharmacological profile of an essential oil derived from Melissa officinalis with anti-agitation properties: focus on ligandgated channels. J Pharm Pharmacol 2008; 60 (3): 377-84 (Pubitemid 351269826)
296. Huang L, Abuhamdah S, Howes MJ, et al. Pharmacological profile of essential oils derived from Lavandula angustifolia and Melissa officinalis with anti-agitation properties: focus on ligand-gated channels. J Pharm Pharmacol 2008; 60 (11): 1515-22
297. Lin PW, Chan WC, Ng BF, et al. Efficacy of aromatherapy (Lavandula angustifolia) as an intervention for agitated behaviours in Chinese older persons with dementia: a cross-over randomized trial. Int J Geriatr Psychiatry 2007; 22 (5): 405-10 (Pubitemid 46831682)
298. Holmes C, Hopkins V, Hensford C, et al. Lavender oil as a treatment for agitated behaviour in severe dementia: a placebo controlled study. Int J Geriatr Psychiatry 2002; 17 (4): 305-8 (Pubitemid 34467087)
299. Snow AL, Hovanec L, Brandt J. A controlled trial of aromatherapy for agitation in nursing home patients with dementia. J Altern Complement Med 2004; 10 (3): 431-7 (Pubitemid 38879927)
300. Thorgrimsen L, Spector A, Wiles A, et al. Aroma therapy for dementia. Cochrane Database Syst Rev 2003; 3: CD003150
301. Burns A, Perry E, Holmes C, et al. A double blind placebo controlled randomised trial of Melissa officinalis oil and donepezil for the treatment of agitation in Alzheimer's disease. Dement Geriatr Cogn Disord 2011; 31 (2): 158-64