Plant alkaloids as drug leads for Alzheimer's disease

Neurochemistry International

Volumn 89, Issue , 2015, Pages 260-270

  Ng, Yu Pong ^a   Or, Terry Cho Tsun ^a   Ip, Nancy Y ^a  

^a HONG KONG UNIVERSITY OF SCIENCE AND TECHNOLOGY   (Hong Kong)

Author keywords

Acetylcholinesterase; Alzheimer's disease; Amyloid beta; Neurodegenerative disease; Neurofibrillary tangles; Neuroinflammation

Indexed keywords

ALKALOID DERIVATIVE; BERBERINE; CAFFEINE; CAPSAICIN; GALANTAMINE; HARMINE; HUPERZINE A; INDIRUBIN; INDOMETACIN; ISORHYNCHOPHYLLINE; MORPHINE; NICOTINE; RHYNCHOPHYLLINE; ALKALOID;

ALZHEIMER DISEASE; ARTICLE; HUMAN; NONHUMAN; PATHOPHYSIOLOGY; PRIORITY JOURNAL; ANIMAL; DRUG DEVELOPMENT; ISOLATION AND PURIFICATION; METABOLISM; PHYTOTHERAPY; PROCEDURES; TRENDS;

ALKALOIDS; ALZHEIMER DISEASE; ANIMALS; DRUG DISCOVERY; HUMANS; PHYTOTHERAPY;

EID: 84942297421     PISSN: 01970186     EISSN: 18729754     Source Type: Journal    
DOI: 10.1016/j.neuint.2015.07.018     Document Type: Review

References (172)

1. A.E. Abd El-Wahab, D.A. Ghareeb, E.E. Sarhan, M.M. Abu-Serie, and M.A. El Demellawy In vitro biological assessment of berberis vulgaris and its active constituent, berberine: antioxidants, anti-acetylcholinesterase, anti-diabetic and anticancer effects BMC Complement. Altern. Med. 13 2013 218
2. P. Agostinho, R.A. Cunha, and C. Oliveira Neuroinflammation, oxidative stress and the pathogenesis of Alzheimer's disease Curr. Pharm. Des. 16 25 2010 2766 2778
3. M. Allgaier, and C. Allgaier An update on drug treatment options of Alzheimer's disease Front. Biosci. (Landmark Ed.) 19 2014 1345 1354
4. F. Amenta, and S.K. Tayebati Pathways of acetylcholine synthesis, transport and release as targets for treatment of adult-onset cognitive dysfunction Curr. Med. Chem. 15 5 2008 488 498
5. V. Amirkia, and M. Heinrich Alkaloids as drug leads - a predictive structural and biodiversity-based analysis Phytochem. Lett. 10 0 2014 xlviii liii
6. G.W. Arendash, T. Mori, C. Cao, M. Mamcarz, M. Runfeldt, A. Dickson, K. Rezai-Zadeh, J. Tane, B.A. Citron, X. Lin, V. Echeverria, and H. Potter Caffeine reverses cognitive impairment and decreases brain amyloid-beta levels in aged Alzheimer's disease mice J. Alzheimers Dis. 17 3 2009 661 680
7. G.W. Arendash, W. Schleif, K. Rezai-Zadeh, E.K. Jackson, L.C. Zacharia, J.R. Cracchiolo, D. Shippy, and J. Tan Caffeine protects Alzheimer's mice against cognitive impairment and reduces brain beta-amyloid production Neuroscience 142 4 2006 941 952
8. M. Asai, N. Iwata, A. Yoshikawa, Y. Aizaki, S. Ishiura, T.C. Saido, and K. Maruyama Berberine alters the processing of Alzheimer's amyloid precursor protein to decrease abeta secretion Biochem. Biophys. Res. Commun. 352 2 2007 498 502
9. ADAPT-FS Research Group Follow-up evaluation of cognitive function in the randomized Alzheimer's disease anti-inflammatory prevention trial and its follow-up study Alzheimers Dement. 11 2 2015 216 225.e211
10. G. Bartzokis, D. Sultzer, J. Mintz, L.E. Holt, P. Marx, C.K. Phelan, and S.R. Marder In vivo evaluation of brain iron in Alzheimer's disease and normal subjects using MRI Biol. Psychiatry 35 7 1994 480 487
11. A. Bernardi, R.L. Frozza, A. Meneghetti, J.B. Hoppe, A.M. Battastini, A.R. Pohlmann, S.S. Guterres, and C.G. Salbego Indomethacin-loaded lipid-core nanocapsules reduce the damage triggered by Aβ1-42 in Alzheimer's disease models Int. J. Nanomedicine 7 2012 4927 4942
12. U. Bickel, T. Thomsen, J.P. Fischer, W. Weber, and H. Kewitz Galanthamine: pharmacokinetics, tissue distribution and cholinesterase inhibition in brain of mice Neuropharmacology 30 5 1991 447 454
13. I. Blasko, M. Stampfer-Kountchev, P. Robatscher, R. Veerhuis, P. Eikelenboom, and B. Grubeck-Loebenstein How chronic inflammation can affect the brain and support the development of Alzheimer's disease in old age: the role of microglia and astrocytes Aging Cell 3 4 2004 169 176
14. K. Blennow, M.J. de Leon, and H. Zetterberg Alzheimer's disease Lancet 368 9533 2006 387 403
15. M. Bonesi, M.R. Loizzo, F. Conforti, N.G. Passalacqua, A. Saab, F. Menichini, and R. Tundis Berberis aetnensis and B. libanotica: a comparative study on the chemical composition, inhibitory effect on key enzymes linked to Alzheimer's disease and antioxidant activity J. Pharm. Pharmacol. 65 12 2013 1726 1735
16. G.M. Bores, F.P. Huger, W. Petko, A.E. Mutlib, F. Camacho, D.K. Rush, D.E. Selk, V. Wolf, R.W. Kosley, L. Davis, and H.M. Vargas Pharmacological evaluation of novel Alzheimer's disease therapeutics: acetylcholinesterase inhibitors related to galanthamine J. Pharmacol. Exp. Ther. 277 2 1996 728 738
17. A.I. Bush The metallobiology of Alzheimer's disease Trends Neurosci. 26 4 2003 207 214
18. C.X. Chen, R.M. Jin, Y.K. Li, J. Zhong, L. Yue, S.C. Chen, and J.Y. Zhou Inhibitory effect of rhynchophylline on platelet aggregation and thrombosis Zhongguo Yao Li Xue Bao 13 2 1992 126 130
19. M. Chen, M. Tan, M. Jing, A. Liu, Q. Liu, S. Wen, Z. Chen, X. Chao, X. He, C. Ramassamy, Y. Gao, and R. Pi Berberine protects homocysteic acid-induced HT-22 cell death: involvement of Akt pathway Metab. Brain Dis. 30 1 2015 137 142
20. Y.F. Chu, W.H. Chang, R.M. Black, J.R. Liu, P. Sompol, Y. Chen, H. Wei, Q. Zhao, and I.H. Cheng Crude caffeine reduces memory impairment and amyloid β(1-42) levels in an Alzheimer's mouse model Food Chem. 135 3 2012 2095 2102
21. L.A. Craig, N.S. Hong, and R.J. McDonald Revisiting the cholinergic hypothesis in the development of Alzheimer's disease Neurosci. Biobehav Rev. 35 6 2011 1397 1409
22. T.P. Cushnie, B. Cushnie, and A.J. Lamb Alkaloids: an overview of their antibacterial, antibiotic-enhancing and antivirulence activities Int. J. Antimicrob. Agents 44 5 2014 377 386
23. O.P. Dall'Igna, P. Fett, M.W. Gomes, D.O. Souza, R.A. Cunha, and D.R. Lara Caffeine and adenosine A(2a) receptor antagonists prevent beta-amyloid (25-35)-induced cognitive deficits in mice Exp. Neurol. 203 1 2007 241 245
24. V.J. De-Paula, M. Radanovic, B.S. Diniz, and O.V. Forlenza Alzheimer's disease Subcell. Biochem. 65 2012 329 352
25. R. Ding, B.F. Sun, and G.Q. Lin An efficient total synthesis of (-)-huperzine A Org. Lett. 14 17 2012 4446 4449
26. Y. Ding, A. Qiao, and G.H. Fan Indirubin-3'-monoxime rescues spatial memory deficits and attenuates beta-amyloid-associated neuropathology in a mouse model of Alzheimer's disease Neurobiol. Dis. 39 2 2010 156 168
27. S.S. Durairajan, Y.Y. Huang, P.Y. Yuen, L.L. Chen, K.Y. Kwok, L.F. Liu, J.X. Song, Q.B. Han, L. Xue, S.K. Chung, J.D. Huang, L. Baum, S. Senapati, and M. Li Effects of huanglian-Jie-Du-Tang and its modified formula on the modulation of amyloid-β precursor protein processing in Alzheimer's disease models PLoS One 9 3 2014 e92954
28. S.S. Durairajan, L.F. Liu, J.H. Lu, L.L. Chen, Q. Yuan, S.K. Chung, L. Huang, X.S. Li, J.D. Huang, and M. Li Berberine ameliorates β-amyloid pathology, gliosis, and cognitive impairment in an Alzheimer's disease transgenic mouse model Neurobiol. Aging 33 12 2012 2903 2919
29. V. Echeverria, R. Zeitlin, S. Burgess, S. Patel, A. Barman, G. Thakur, M. Mamcarz, L. Wang, D.B. Sattelle, D.A. Kirschner, T. Mori, R.M. Leblanc, R. Prabhakar, and G.W. Arendash Cotinine reduces amyloid-β aggregation and improves memory in Alzheimer's disease mice J. Alzheimers Dis. 24 4 2011 817 835
30. J. Egea, M.D. Martín-de-Saavedra, E. Parada, A. Romero, L. Del Barrio, A.O. Rosa, A.G. García, and M.G. López Galantamine elicits neuroprotection by inhibiting iNOS, NADPH oxidase and ROS in hippocampal slices stressed with anoxia/reoxygenation Neuropharmacology 62 2 2012 1082 1090
31. M.H. Eskelinen, and M. Kivipelto Caffeine as a protective factor in dementia and Alzheimer's disease J. Alzheimers Dis. 20 Suppl. 1 2010 S167 S174
32. G. Farías, A. Cornejo, J. Jiménez, L. Guzmán, and R.B. Maccioni Mechanisms of tau self-aggregation and neurotoxicity Curr. Alzheimer Res. 8 6 2011 608 614
33. D. Frost, B. Meechoovet, T. Wang, S. Gately, M. Giorgetti, I. Shcherbakova, and T. Dunckley β-carboline compounds, including harmine, inhibit DYRK1A and tau phosphorylation at multiple Alzheimer's disease-related sites PLoS One 6 5 2011 e19264
34. B.B. Fredholm, K. Bättig, J. Holmén, A. Nehlig, and E.E. Zvartau Actions of caffeine in the brain with special reference to factors that contribute to its widespread use Pharmacol. Rev. 51 1 1999 83 133
35. A.K. Fu, K.W. Hung, H. Huang, S. Gu, Y. Shen, E.Y. Cheng, F.C. Ip, X. Huang, W.Y. Fu, and N.Y. Ip Blockade of EphA4 signaling ameliorates hippocampal synaptic dysfunctions in mouse models of Alzheimer's disease Proc. Natl. Acad. Sci. U. S. A. 111 27 2014 9959 9964
36. X. Gao, and X.C. Tang Huperzine A attenuates mitochondrial dysfunction in beta-amyloid-treated PC12 cells by reducing oxygen free radicals accumulation and improving mitochondrial energy metabolism J. Neurosci. Res. 83 6 2006 1048 1057
37. X. Gao, C.Y. Zheng, L. Yang, X.C. Tang, and H.Y. Zhang Huperzine A protects isolated rat brain mitochondria against beta-amyloid peptide Free Radic. Biol. Med. 46 11 2009 1454 1462
38. N. Göckler, G. Jofre, C. Papadopoulos, U. Soppa, F.J. Tejedor, and W. Becker Harmine specifically inhibits protein kinase DYRK1A and interferes with neurite formation FEBS J. 276 21 2009 6324 6337
39. R.K. Gordon, S.V. Nigam, J.A. Weitz, J.R. Dave, B.P. Doctor, and H.S. Ved The NMDA receptor ion channel: a site for binding of Huperzine A J. Appl. Toxicol. 21 Suppl. 1 2001 S47 S51
40. L. Guzmán-Martinez, G.A. Farías, and R.B. Maccioni Tau oligomers as potential targets for Alzheimer's diagnosis and novel drugs Front. Neurol. 4 2013 167
41. A.L. Harvey The pharmacology of galanthamine and its analogues Pharmacol. Ther. 68 1 1995 113 128
42. M. Heinrich, and H. Lee Teoh Galanthamine from snowdrop-the development of a modern drug against Alzheimer's disease from local caucasian knowledge J. Ethnopharmacol. 92 2-3 2004 147 162
43. M.T. Heneka, M.J. Carson, J.E. Khoury, G.E. Landreth, F. Brosseron, D.L. Feinstein, A.H. Jacobs, T. Wyss-Coray, J. Vitorica, R.M. Ransohoff, K. Herrup, S.A. Frautschy, B. Finsen, G.C. Brown, A. Verkhratsky, K. Yamanaka, J. Koistinaho, E. Latz, A. Halle, G.C. Petzold, T. Town, D. Morgan, M.L. Shinohara, V.H. Perry, C. Holmes, N.G. Bazan, D.J. Brooks, S. Hunot, B. Joseph, N. Deigendesch, O. Garaschuk, E. Boddeke, C.A. Dinarello, J.C. Breitner, G.M. Cole, D.T. Golenbock, and M.P. Kummer Neuroinflammation in Alzheimer's disease Lancet Neurol. 14 4 2015 388 405
44. M.T. Heneka, M.P. Kummer, S. Weggen, B. Bulic, G. Multhaup, L. Münter, M. Hüll, T. Pflanzner, and C.U. Pietrzik Molecular mechanisms and therapeutic application of NSAIDs and derived compounds in Alzheimer's disease Curr. Alzheimer Res. 8 2 2011 115 131
45. M.N. Howe, and I.R. Price Effects of transdermal nicotine on learning, memory, verbal fluency, concentration, and general health in a healthy sample at risk for dementia Int. Psychogeriatr. 13 4 2001 465 475
46. C.L. Hsieh, T.Y. Ho, S.Y. Su, W.Y. Lo, C.H. Liu, and N.Y. Tang Uncaria rhynchophylla and Rhynchophylline inhibit c-Jun N-terminal kinase phosphorylation and nuclear factor-kappaB activity in kainic acid-treated rats Am. J. Chin. Med. 37 2 2009 351 360
47. Y. Hu, J. Zhang, O. Chandrashankra, F.C. Ip, and N.Y. Ip Design, synthesis and evaluation of novel heterodimers of donepezil and huperzine fragments as acetylcholinesterase inhibitors Bioorg Med. Chem. 21 3 2013 676 683
48. X.T. Huang, Z.M. Qian, X. He, Q. Gong, K.C. Wu, L.R. Jiang, L.N. Lu, Z.J. Zhu, H.Y. Zhang, W.H. Yung, and Y. Ke Reducing iron in the brain: a novel pharmacologic mechanism of huperzine A in the treatment of Alzheimer's disease Neurobiol. Aging 35 5 2014 1045 1054
49. IUPAC Compendium of Chemical Terminology, (The "Gold Book") second ed. 1997 Blackwell Scientific Publications Oxford
50. L. Jia, J. Liu, Z. Song, X. Pan, L. Chen, X. Cui, and M. Wang Berberine suppresses amyloid-beta-induced inflammatory response in microglia by inhibiting nuclear factor-kappaB and mitogen-activated protein kinase signalling pathways J. Pharm. Pharmacol. 64 10 2012 1510 1521
51. X. Jiang, L.W. Jia, X.H. Li, X.S. Cheng, J.Z. Xie, Z.W. Ma, W.J. Xu, Y. Liu, Y. Yao, L.L. Du, and X.W. Zhou Capsaicin ameliorates stress-induced Alzheimer's disease-like pathological and cognitive impairments in rats J. Alzheimers Dis. 35 1 2013 91 105
52. H.A. Jung, B.S. Min, T. Yokozawa, J.H. Lee, Y.S. Kim, and J.S. Choi Anti-Alzheimer and antioxidant activities of coptidis rhizoma alkaloids Biol. Pharm. Bull. 32 8 2009 1433 1438
53. C.M. Karch, C. Cruchaga, and A.M. Goate Alzheimer's disease genetics: from the bench to the clinic Neuron 83 1 2014 11 26
54. P. Kása, Z. Rakonczay, and K. Gulya The cholinergic system in Alzheimer's disease Prog. Neurobiol. 52 6 1997 511 535
55. V. Kettmann, D. Kosfálová, S. Jantová, M. Cernáková, and J. Drímal In vitro cytotoxicity of berberine against HeLa and L1210 cancer cell lines Pharmazie 59 7 2004 548 551
56. T. Kihara, H. Sawada, T. Nakamizo, R. Kanki, H. Yamashita, A. Maelicke, and S. Shimohama Galantamine modulates nicotinic receptor and blocks abeta-enhanced glutamate toxicity Biochem. Biophys. Res. Commun. 325 3 2004 976 982
57. Y.S. Kim, S.M. Kwak, and S.K. Myung Caffeine intake from coffee or tea and cognitive disorders: a meta-analysis of observational studies Neuroepidemiology 44 1 2015 51 63
58. 1 muscarinic and α7 nicotinic receptors in mice Int. J. Neuropsychopharmacol. 17 12 2014 1957 1968
59. E.L. Konrath, C.o.S. Passos, L.C. Klein, and A.T. Henriques Alkaloids as a source of potential anticholinesterase inhibitors for the treatment of Alzheimer's disease J. Pharm. Pharmacol. 65 12 2013 1701 1725
60. D. Krstic, and I. Knuesel Deciphering the mechanism underlying late-onset Alzheimer disease Nat. Rev. Neurol. 9 1 2013 25 34
61. A. Kumar, A. Singh, and Ekavali A review on Alzheimer's disease pathophysiology and its management: an update Pharmacol. Rep. 67 2 2015 195 203
62. E. Küpeli, M. Koşar, E. Yeşilada, K. Hüsnü, and C. Başer A comparative study on the anti-inflammatory, antinociceptive and antipyretic effects of isoquinoline alkaloids from the roots of Turkish berberis species Life Sci. 72 6 2002 645 657
63. K. Kysenius, C.A. Brunello, and H.J. Huttunen Mitochondria and NMDA receptor-dependent toxicity of berberine sensitizes neurons to glutamate and rotenone injury PLoS One 9 9 2014 e107129
64. C. Laurent, S. Eddarkaoui, M. Derisbourg, A. Leboucher, D. Demeyer, S. Carrier, M. Schneider, M. Hamdane, C.E. Müller, L. Buée, and D. Blum Beneficial effects of caffeine in a transgenic model of Alzheimer's disease-like tau pathology Neurobiol. Aging 35 9 2014 2079 2090
65. A. Laux-Biehlmann, J. Mouheiche, J. Vérièpe, and Y. Goumon Endogenous morphine and its metabolites in mammals: history, synthesis, localization and perspectives Neuroscience 233 2013 95 117
66. A.D. Lawrence, and B.J. Sahakian The cognitive psychopharmacology of Alzheimer's disease: focus on cholinergic systems Neurochem. Res. 23 5 1998 787 794
67. M. Le Moal, and G.F. Koob Drug addiction: pathways to the disease and pathophysiological perspectives Eur. Neuropsychopharmacol. 17 6-7 2007 377 393
68. S. Leclerc, M. Garnier, R. Hoessel, D. Marko, J.A. Bibb, G.L. Snyder, P. Greengard, J. Biernat, Y.Z. Wu, E.M. Mandelkow, G. Eisenbrand, and L. Meijer Indirubins inhibit glycogen synthase kinase-3 beta and CDK5/p25, two protein kinases involved in abnormal tau phosphorylation in Alzheimer's disease. A property common to most cyclin-dependent kinase inhibitors? J. Biol. Chem. 276 1 2001 251 260
69. J.R. Leon-Carmona, and A. Galano Uric and 1-methyluric acids: metabolic wastes or antiradical protectors? J. Phys. Chem. B 115 51 2011 15430 15438
70. S. Letasiová, S. Jantová, L. Cipák, and M. Múcková Berberine-antiproliferative activity in vitro and induction of apoptosis/necrosis of the U937 and B16 cells Cancer Lett. 239 2 2006 254 262
71. J. Li, H.M. Wu, R.L. Zhou, G.J. Liu, and B.R. Dong Huperzine A for Alzheimer's disease Cochrane Database Syst. Rev. 2 2008 CD005592
72. P.Y. Li, X.R. Zeng, J. Cheng, J. Wen, I. Inoue, and Y. Yang Rhynchophylline-induced vasodilation in human mesenteric artery is mainly due to blockage of L-type calcium channels in vascular smooth muscle cells Naunyn Schmiedeb. Arch. Pharmacol. 386 11 2013 973 982
73. Y.F. Liao, B.J. Wang, H.T. Cheng, L.H. Kuo, and M.S. Wolfe Tumor necrosis factor-alpha, interleukin-1beta, and interferon-gamma stimulate gamma-secretase-mediated cleavage of amyloid precursor protein through a JNK-dependent MAPK pathway J. Biol. Chem. 279 47 2004 49523 49532
74. J.S. Liu, Y.L. Zhu, C.M. Yu, Y.Z. Zhou, Y.Y. Han, F.W. Wu, and B.F. Qi The structures of huperzine A and B, two new alkaloids exhibiting marked anticholinesterase activity Can. J. Chem. 64 4 1986 837 839
75. X. Liu, J. Zhou, M.D. Abid, H. Yan, H. Huang, L. Wan, Z. Feng, and J. Chen Berberine attenuates axonal transport impairment and axonopathy induced by calyculin A in N2a cells PLoS One 9 4 2014 e93974
76. A. Lloret, T. Fuchsberger, E. Giraldo, and J. Viña Molecular mechanisms linking amyloid β toxicity and Tau hyperphosphorylation in Alzheimer's disease Free Radic. Biol. Med. 83 2015 186 191
77. J.J. Lu, W. Pan, Y.J. Hu, and Y.T. Wang Multi-target drugs: the trend of drug research and development PLoS One 7 6 2012 e40262
78. L. Ma, P. Xiao, B. Guo, J. Wu, F. Liang, and S. Dong Cerebral protective effects of some compounds isolated from traditional Chinese herbs Zhongguo Zhong Yao Za Zhi 24 4 1999 238 239 256-inside back cover
79. T. Ma, K. Gong, Y. Yan, L. Zhang, P. Tang, X. Zhang, and Y. Gong Huperzine A promotes hippocampal neurogenesis in vitro and in vivo Brain Res. 1506 2013 35 43
80. X. Ma, and D.R. Gang In vitro production of huperzine A, a promising drug candidate for Alzheimer's disease Phytochemistry 69 10 2008 2022 2028
81. X. Ma, C. Tan, D. Zhu, D.R. Gang, and P. Xiao Huperzine A from Huperzia species-an ethnopharmacolgical review J. Ethnopharmacol. 113 1 2007 15 34
82. L. Maia, and A. de Mendonça Does caffeine intake protect from Alzheimer's disease? Eur. J. Neurol. 9 4 2002 377 382
83. M.D. Mashkovsky, and R.P. Kruglikova-Lvova On the Pharmacology of the New Alkaloid Galantamine (14) 1951 27 30
84. B. Matharu, G. Gibson, R. Parsons, T.N. Huckerby, S.A. Moore, L.J. Cooper, R. Millichamp, D. Allsop, and B. Austen Galantamine inhibits beta-amyloid aggregation and cytotoxicity J. Neurol. Sci. 280 1-2 2009 49 58
85. K. Matsuzono, N. Hishikawa, Y. Ohta, T. Yamashita, K. Deguchi, Y. Nakano, and K. Abe Combination therapy of cholinesterase inhibitor (Donepezil or galantamine) plus memantine in the okayama memantine study J. Alzheimers Dis. 45 3 2015 771 780
86. J.B. Melo, C. Sousa, P. Garção, C.R. Oliveira, and P. Agostinho Galantamine protects against oxidative stress induced by amyloid-beta peptide in cortical neurons Eur. J. Neurosci. 29 3 2009 455 464
87. M.A. Meraz-Ríos, D. Toral-Rios, D. Franco-Bocanegra, J. Villeda-Hernández, and V. Campos-Peña Inflammatory process in Alzheimer's Disease Front. Integr. Neurosci. 7 2013 59
88. R.A. Meyers Encyclopedia of Physical Science and Technology - Alkaloids third ed. 2002 Academic Press
89. D.M. Michaelson APOE ε4: the most prevalent yet understudied risk factor for Alzheimer's disease Alzheimers Dement. 10 6 2014 861 868
90. C. Millington, S. Sonego, N. Karunaweera, A. Rangel, J.R. Aldrich-Wright, I.L. Campbell, E. Gyengesi, and G. Münch Chronic neuroinflammation in Alzheimer's disease: new perspectives on animal models and promising candidate drugs Biomed. Res. Int. 2014 2014 309129
91. L.F. Miranda, K.B. Gomes, J.N. Silveira, G.A. Pianetti, R.M. Byrro, P.R. Peles, F.H. Pereira, T.R. Santos, A.G. Assini, V.V. Ribeiro, P.A. Tito, R.O. Matoso, T.O. Lima, E.N. Moraes, and P. Caramelli Predictive factors of clinical response to cholinesterase inhibitors in mild and moderate Alzheimer's disease and mixed dementia: a one-year naturalistic study J. Alzheimers Dis. 45 2 2015 609 620
92. J. Mitsui, and S. Tsuji Genomic aspects of sporadic neurodegenerative diseases Biochem. Biophys. Res. Commun. 452 2 2014 221 225
93. A.F. Mohamed, K. Matsumoto, K. Tabata, H. Takayama, M. Kitajima, and H. Watanabe Effects of Uncaria tomentosa total alkaloid and its components on experimental amnesia in mice: elucidation using the passive avoidance test J. Pharm. Pharmacol. 52 12 2000 1553 1561
94. I. Morales, L. Guzmán-Martínez, C. Cerda-Troncoso, G.A. Farías, and R.B. Maccioni Neuroinflammation in the pathogenesis of Alzheimer's disease. A rational framework for the search of novel therapeutic approaches Front. Cell Neurosci. 8 2014 112
95. National Institute on Aging Alzheimer's Disease Medications Fact Sheet Alzheimer's Disease Medications Fact Sheet National Institutes of Health 2015
96. A. Nehlig Are we dependent upon coffee and caffeine? A review on human and animal data Neurosci. Biobehav Rev. 23 4 1999 563 576
97. I.E. Orhan, G. Orhan, and E. Gurkas An overview on natural cholinesterase inhibitors-a multi-targeted drug class-and their mass production Mini Rev. Med. Chem. 11 10 2011 836 842
98. M. Pákáski, M. Hugyecz, P. Sántha, G. Jancsó, A. Bjelik, A. Domokos, Z. Janka, and J. Kálmán Capsaicin promotes the amyloidogenic route of brain amyloid precursor protein processing Neurochem. Int. 54 7 2009 426 430
99. N. Panahi, M. Mahmoudian, P. Mortazavi, and G.S. Hashjin Effects of berberine on β-secretase activity in a rabbit model of Alzheimer's disease Arch. Med. Sci. 9 1 2013 146 150
100. W. Parys Development of Reminyl (R) (Galantamine), a Novel Acetylcholinesterase Inhibitor, for the Treatment of Alzheimer's Disease,Alzheimer's Report 1998 S19 S20
101. G. Pasternak, and Y.X. Pan Mu opioid receptors in pain management Acta Anaesthesiol. Taiwan 49 1 2011 21 25
102. A.C. Paula-Lima, J. Brito-Moreira, and S.T. Ferreira Deregulation of excitatory neurotransmission underlying synapse failure in Alzheimer's disease J. Neurochem. 126 2 2013 191 202
103. J.R. Prasanthi, B. Dasari, G. Marwarha, T. Larson, X. Chen, J.D. Geiger, and O. Ghribi Caffeine protects against oxidative stress and Alzheimer's disease-like pathology in rabbit hippocampus induced by cholesterol-enriched diet Free Radic. Biol. Med. 49 7 2010 1212 1220
104. L. Qian, K.S. Tan, S.J. Wei, H.M. Wu, Z. Xu, B. Wilson, R.B. Lu, J.S. Hong, and P.M. Flood Microglia-mediated neurotoxicity is inhibited by morphine through an opioid receptor-independent reduction of NADPH oxidase activity J. Immunol. 179 2 2007 1198 1209
105. L. Racková, M. Májeková, D. Kost'álová, and M. Stefek Antiradical and antioxidant activities of alkaloids isolated from mahonia aquifolium. Structural aspects Bioorg Med. Chem. 12 17 2004 4709 4715
106. M.S. Rafii, S. Walsh, J.T. Little, K. Behan, B. Reynolds, C. Ward, S. Jin, R. Thomas, P.S. Aisen, and Study, A.S.D.C A phase II trial of huperzine A in mild to moderate Alzheimer disease Neurology 76 16 2011 1389 1394
107. S. Rambhia, K.J. Mantione, G.B. Stefano, and P. Cadet Morphine modulation of the ubiquitin-proteasome complex is neuroprotective Med. Sci. Monit. 11 11 2005 BR386 396
108. M.L. Raves, M. Harel, Y.P. Pang, I. Silman, A.P. Kozikowski, and J.L. Sussman Structure of acetylcholinesterase complexed with the nootropic alkaloid, (-)-huperzine A Nat. Struct. Biol. 4 1 1997 57 63
109. U. Richarz, M. Gaudig, K. Rettig, and B. Schauble Galantamine treatment in outpatients with mild Alzheimer's disease Acta Neurol. Scand. 129 6 2014 382 392
110. S.R. Ryoo, H.K. Jeong, C. Radnaabazar, J.J. Yoo, H.J. Cho, H.W. Lee, I.S. Kim, Y.H. Cheon, Y.S. Ahn, S.H. Chung, and W.J. Song DYRK1A-mediated hyperphosphorylation of Tau. A functional link between Down syndrome and Alzheimer disease J. Biol. Chem. 282 48 2007 34850 34857
111. S. Schneider, L A critical review of cholinesterase inhibitors as a treatment modality in Alzheimer's disease Dialogues Clin. Neurosci. 2 2 2000 111 128
112. A.R. Salomon, K.J. Marcinowski, R.P. Friedland, and M.G. Zagorski Nicotine inhibits amyloid formation by the beta-peptide Biochemistry 35 42 1996 13568 13578
113. L.S. Schneider, F. Mangialasche, N. Andreasen, H. Feldman, E. Giacobini, R. Jones, V. Mantua, P. Mecocci, L. Pani, B. Winblad, and M. Kivipelto Clinical trials and late-stage drug development for Alzheimer's disease: an appraisal from 1984 to 2014 J. Intern Med. 275 3 2014 251 283
114. A. Schrattenholz, E.F. Pereira, U. Roth, K.H. Weber, E.X. Albuquerque, and A. Maelicke Agonist responses of neuronal nicotinic acetylcholine receptors are potentiated by a novel class of allosterically acting ligands Mol. Pharmacol. 49 1 1996 1 6
115. L.J. Scott, and K.L. Goa Galantamine: a review of its use in Alzheimer's disease Drugs 60 5 2000 1095 1122
116. M.L. Selenica, H.S. Jensen, A.K. Larsen, M.L. Pedersen, L. Helboe, M. Leist, and J. Lotharius Efficacy of small-molecule glycogen synthase kinase-3 inhibitors in the postnatal rat model of tau hyperphosphorylation Br. J. Pharmacol. 152 6 2007 959 979
117. Z.Q. Shao Comparison of the efficacy of four cholinesterase inhibitors in combination with memantine for the treatment of Alzheimer's disease Int. J. Clin. Exp. Med. 8 2 2015 2944 2948
118. J.S. Shi, J.X. Yu, X.P. Chen, and R.X. Xu Pharmacological actions of Uncaria alkaloids, rhynchophylline and isorhynchophylline Acta Pharmacol. Sin. 24 2 2003 97 101
119. S.B. Shim, S.H. Lee, K.R. Chae, C.K. Kim, D.Y. Hwang, B.G. Kim, S.W. Jee, J.S. Sin, C.J. Bae, B.C. Lee, H.H. Lee, and Y.K. Kim Nicotine leads to improvements in behavioral impairment and an increase in the nicotine acetylcholine receptor in transgenic mice Neurochem. Res. 33 9 2008 1783 1788
120. M. Shinohara, S. Fujioka, M.E. Murray, A. Wojtas, M. Baker, A. Rovelet-Lecrux, R. Rademakers, P. Das, J.E. Parisi, N.R. Graff-Radford, R.C. Petersen, D.W. Dickson, and G. Bu Regional distribution of synaptic markers and APP correlate with distinct clinicopathological features in sporadic and familial Alzheimer's disease Brain 137 Pt 5 2014 1533 1549
121. K.S. Shin, H.S. Choi, T.T. Zhao, K.H. Suh, I.H. Kwon, S.O. Choi, and M.K. Lee Neurotoxic effects of berberine on long-term L-DOPA administration in 6-hydroxydopamine-lesioned rat model of Parkinson's disease Arch. Pharm. Res. 36 6 2013 759 767
122. A.A. Skolnick Screening to help asthmatics breathe easier JAMA 277 24 1997 1921-1921
123. A. Smith Effects of caffeine on human behavior Food Chem. Toxicol. 40 9 2002 1243 1255
124. M.A. Smith, X. Zhu, M. Tabaton, G. Liu, D.W. McKeel, M.L. Cohen, X. Wang, S.L. Siedlak, B.E. Dwyer, T. Hayashi, M. Nakamura, A. Nunomura, and G. Perry Increased iron and free radical generation in preclinical Alzheimer disease and mild cognitive impairment J. Alzheimers Dis. 19 1 2010 363 372
125. A. Soldano, and B.A. Hassan Beyond pathology: APP, brain development and Alzheimer's disease Curr. Opin. Neurobiol. 27 2014 61 67
126. R. Sperling, E. Mormino, and K. Johnson The evolution of preclinical Alzheimer's disease: implications for prevention trials Neuron 84 3 2014 608 622
127. I.C. Stancu, B. Vasconcelos, D. Terwel, and I. Dewachter Models of β-amyloid induced Tau-pathology: the long and "folded" road to understand the mechanism Mol. Neurodegener. 9 2014 51
128. J. Su, and M. Yang Huperzine A production by paecilomyces tenuis YS-13, an endophytic fungus isolated from Huperzia serrata Nat. Prod. Res. 29 11 2015 1035 1041
129. T. Su, S. Xie, H. Wei, J. Yan, L. Huang, and X. Li Synthesis and biological evaluation of berberine-thiophenyl hybrids as multi-functional agents: inhibition of acetylcholinesterase, butyrylcholinesterase, and Aβ aggregation and antioxidant activity Bioorg Med. Chem. 21 18 2013 5830 5840
130. Y. Takada-Takatori, T. Kume, M. Sugimoto, H. Katsuki, T. Niidome, H. Sugimoto, T. Fujii, S. Okabe, and A. Akaike Neuroprotective effects of galanthamine and tacrine against glutamate neurotoxicity Eur. J. Pharmacol. 549 1-3 2006 19 26
131. L.L. Tang, R. Wang, and X.C. Tang 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. 26 6 2005 673 678
132. L.L. Tang, R. Wang, and X.C. Tang Huperzine A protects SHSY5Y neuroblastoma cells against oxidative stress damage via nerve growth factor production Eur. J. Pharmacol. 519 1-2 2005 9 15
133. X.C. Tang, P. De Sarno, K. Sugaya, and E. Giacobini Effect of huperzine A, a new cholinesterase inhibitor, on the central cholinergic system of the rat J. Neurosci. Res. 24 2 1989 276 285
134. X.C. Tang, G.H. Kindel, A.P. Kozikowski, and I. Hanin Comparison of the effects of natural and synthetic huperzine-A on rat brain cholinergic function in vitro and in vivo J. Ethnopharmacol. 44 3 1994 147 155
135. T. Thomsen, U. Bickel, J.P. Fischer, and H. Kewitz Stereoselectivity of cholinesterase inhibition by galanthamine and tolerance in humans Eur. J. Clin. Pharmacol. 39 6 1990 603 605
136. Q.L. Tran, Y. Tezuka, J.Y. Ueda, N.T. Nguyen, Y. Maruyama, K. Begum, H.S. Kim, Y. Wataya, Q.K. Tran, and S. Kadota In vitro antiplasmodial activity of antimalarial medicinal plants used in vietnamese traditional medicine J. Ethnopharmacol. 86 2-3 2003 249 252
137. C.H. Trepanier, and N.W. Milgram Neuroinflammation in Alzheimer's disease: are NSAIDs and selective COX-2 inhibitors the next line of therapy? J. Alzheimers Dis. 21 4 2010 1089 1099
138. D. Tsvetkova, D. Obreshkova, D. Zheleva-Dimitrova, and L. Saso Antioxidant activity of galantamine and some of its derivatives Curr. Med. Chem. 20 36 2013 4595 4608
139. S. Tu, S. Okamoto, S.A. Lipton, and H. Xu Oligomeric Aβ-induced synaptic dysfunction in Alzheimer's disease Mol. Neurodegener. 9 2014 48
140. E. Vartiainen, P. Puska, P. Jousilahti, H.J. Korhonen, J. Tuomilehto, and A. Nissinen Twenty-year trends in coronary risk factors in north Karelia and in other areas of Finland Int. J. Epidemiol. 23 3 1994 495 504
141. H. Wang, and X.C. Tang Anticholinesterase effects of huperzine A, E2020, and tacrine in rats Zhongguo Yao Li Xue Bao 19 1 1998 27 30
142. H.Y. Wang, D.H. Lee, M.R. D'Andrea, P.A. Peterson, R.P. Shank, and A.B. Reitz beta-Amyloid(1-42) binds to alpha7 nicotinic acetylcholine receptor with high affinity. Implications for Alzheimer's disease pathology J. Biol. Chem. 275 8 2000 5626 5632
143. R. Wang, X.Q. Xiao, and X.C. Tang Huperzine A attenuates hydrogen peroxide-induced apoptosis by regulating expression of apoptosis-related genes in rat PC12 cells Neuroreport 12 12 2001 2629 2634
144. R. Wang, H. Yan, and X.-c Tang Progress in studies of huperzine A, a natural cholinesterase inhibitor from Chinese herbal medicine Acta Pharmacol. Sin. 27 1 2006 1 26
145. R. Wang, H.Y. Zhang, and X.C. Tang Huperzine A attenuates cognitive dysfunction and neuronal degeneration caused by beta-amyloid protein-(1-40) in rat Eur. J. Pharmacol. 421 3 2001 149 156
146. X. Wang, R. Wang, D. Xing, H. Su, C. Ma, Y. Ding, and L. Du Kinetic difference of berberine between hippocampus and plasma in rat after intravenous administration of coptidis rhizoma extract Life Sci. 77 24 2005 3058 3067
147. X.D. Wang, J.M. Zhang, H.H. Yang, and G.Y. Hu Modulation of NMDA receptor by huperzine A in rat cerebral cortex Zhongguo Yao Li Xue Bao 20 1 1999 31 35
148. Y.E. Wang, D.X. Yue, and X.C. Tang Anti-cholinesterase activity of huperzine A Zhongguo Yao Li Xue Bao 7 2 1986 110 113
149. Z.F. Wang, L.L. Tang, H. Yan, Y.J. Wang, and X.C. Tang Effects of huperzine A on memory deficits and neurotrophic factors production after transient cerebral ischemia and reperfusion in mice Pharmacol. Biochem. Behav. 83 4 2006 603 611
150. S. West, and P. Bhugra Emerging drug targets for Aβ and tau in Alzheimer's disease: a systematic review Br. J. Clin. Pharmacol. 80 2 2015 221 234
151. H.K. White, and E.D. Levin Four-week nicotine skin patch treatment effects on cognitive performance in Alzheimer's disease Psychopharmacol. Berl. 143 2 1999 158 165
152. G. Wilcock, I. Howe, H. Coles, S. Lilienfeld, L. Truyen, Y. Zhu, R. Bullock, P. Kershaw, and G.-G.-S. Group A long-term comparison of galantamine and donepezil in the treatment of Alzheimer's disease Drugs Aging 20 10 2003 777 789
153. D.S. Woodruff-Pak, R.W. Vogel, and G.L. Wenk Galantamine: effect on nicotinic receptor binding, acetylcholinesterase inhibition, and learning Proc. Natl. Acad. Sci. U. S. A. 98 4 2001 2089 2094
154. M. Xia, X. Cheng, R. Yi, D. Gao, and J. Xiong The binding receptors of aβ: an alternative therapeutic target for Alzheimer's disease Mol. Neurobiol. 2014 10.1007/s12035-014-8994-0
155. Y.-F. Xian, Q.-Q. Mao, J.C.Y. Wu, Z.-R. Su, J.-N. Chen, X.-P. Lai, S.-P. Ip, and Z.-X. Lin Isorhynchophylline treatment improves the amyloid-β-induced cognitive impairment in rats via inhibition of neuronal apoptosis and tau protein hyperphosphorylation J. Alzheimers Dis. 39 2 2014 331 346
156. Y.F. Xian, Z.X. Lin, Q.Q. Mao, J.N. Chen, Z.R. Su, X.P. Lai, and P.S. Ip Isorhynchophylline protects PC12 cells against beta-amyloid-induced apoptosis via PI3K/Akt signaling pathway Evid. Based Complement. Altern. Med. 2013 2013 163057
157. Y.F. Xian, Z.X. Lin, Q.Q. Mao, Z. Hu, M. Zhao, C.T. Che, and S.P. Ip Bioassay-guided Isolation of neuroprotective compounds from uncaria rhynchophylla against beta-amyloid-induced neurotoxicity Evid. Based Complement. Altern. Med. 2012 2012 802625
158. Y.F. Xian, Z.X. Lin, Q.Q. Mao, S.P. Ip, Z.R. Su, and X.P. Lai Protective effect of isorhynchophylline against β-amyloid-induced neurotoxicity in PC12 cells Cell Mol. Neurobiol. 32 3 2012 353 360
159. X.Q. Xiao, H.Y. Zhang, and X.C. Tang Huperzine A attenuates amyloid beta-peptide fragment 25-35-induced apoptosis in rat cortical neurons via inhibiting reactive oxygen species formation and caspase-3 activation J. Neurosci. Res. 67 1 2002 30 36
160. R. Yan, Z. Zhang, Y. Wang, H. Yang, Q. Zeng, and D. Zhu Efficient strategy for maintaining and enhancing the huperzine A production of Shiraia sp. Slf14 through inducer elicitation J. Ind. Microbiol. Biotechnol. 41 7 2014 1175 1179
161. G. Yang, Y. Wang, J. Tian, and J.P. Liu Huperzine A for Alzheimer's disease: a systematic review and meta-analysis of randomized clinical trials PLoS One 8 9 2013 e74916
162. L. Yang, C.Y. Ye, X.T. Huang, X.C. Tang, and H.Y. Zhang Decreased accumulation of subcellular amyloid-β with improved mitochondrial function mediates the neuroprotective effect of huperzine A J. Alzheimers Dis. 31 1 2012 131 142
163. M. Ye, S. Fu, R. Pi, and F. He Neuropharmacological and pharmacokinetic properties of berberine: a review of recent research J. Pharm. Pharmacol. 61 7 2009 831 837
164. G. Yu, Y. Li, Q. Tian, R. Liu, Q. Wang, J.Z. Wang, and X. Wang Berberine attenuates calyculin A-induced cytotoxicity and Tau hyperphosphorylation in HEK293 cells J. Alzheimers Dis. 24 3 2011 525 535
165. R. Zeitlin, S. Patel, S. Burgess, G.W. Arendash, and V. Echeverria Caffeine induces beneficial changes in PKA signaling and JNK and ERK activities in the striatum and cortex of Alzheimer's transgenic mice Brain Res. 1417 2011 127 136
166. J.M. Zhang, and G.Y. Hu Huperzine A, a nootropic alkaloid, inhibits N-methyl-D-aspartate-induced current in rat dissociated hippocampal neurons Neuroscience 105 3 2001 663 669
167. W.B. Zhang, C.X. Chen, S.M. Sim, and C.Y. Kwan In vitro vasodilator mechanisms of the indole alkaloids rhynchophylline and isorhynchophylline, isolated from the hook of Uncaria rhynchophylla (Miquel) Naunyn Schmiedeb. Arch. Pharmacol. 369 2 2004 232 238
168. Y.H. Zhang, X.Y. Zhao, X.Q. Chen, Y. Wang, H.H. Yang, and G.Y. Hu Spermidine antagonizes the inhibitory effect of huperzine A on [3H]dizocilpine (MK-801) binding in synaptic membrane of rat cerebral cortex Neurosci. Lett. 319 2 2002 107 110
169. L. Zheng, Z. Zhou, D. Tao, and T. Lan Protective effect of berberine on cardiac myocyte injured by ischemia-reperfusion Sichuan Da Xue Xue Bao Yi Xue Ban. 34 3 2003 452 454
170. J. Zhou, Y. Fu, and X.C. Tang Huperzine A protects rat pheochromocytoma cells against oxygen-glucose deprivation Neuroreport 12 10 2001 2073 2077
171. J. Zhou, and S. Zhou Antihypertensive and neuroprotective activities of rhynchophylline: the role of rhynchophylline in neurotransmission and ion channel activity J. Ethnopharmacol. 132 1 2010 15 27
172. J.Y. Zhou, and S.W. Zhou Isorhynchophylline: a plant alkaloid with therapeutic potential for cardiovascular and central nervous system diseases Fitoterapia 83 4 2012 617 626