Archives of Pharmacal Research

, Volume 33, Issue 10, pp 1589–1609 | Cite as

Potential therapeutic agents against Alzheimer’s disease from natural sources

Review

Abstract

The average human life span in developed countries has increased to more than 80 years following rapid breakthrough and developments in modern medicine and science, resulting in prolonged life expectancy and increase in the population counts of the geriatric age group. This translates into a dramatic increase in disease burden of elderly patients suffering from senile disorders including neurodegenerative diseases, particularly Alzheimer’s disease (AD). AD is characterized by the death of nerve cells in the cerebral cortex and is the most common subtype of dementia that affected 25 million people worldwide in 2000 and is expected to increase to 114 million by 2050. Despite the exponential growth in the number of AD patients, only acetylcholinesterase (AChE) inhibitors are being currently used to treat AD. It is well known that AChE inhibitors can alleviate the symptoms of AD but not halt the disease progression. Consequently, therapeutic agents against AD acting at various pathologic levels are needed. In the recent decade, natural products with anti-AD properties have attracted much attention. But very few natural products have been investigated in a scientifically justifiable method for these biological activities. Following a detailed research process, it is certain that natural products have a strong potential to develop biologically active compounds with new chemical structures. Many studies have been carried out to identify the naturally occurring anti-AD agents. This review article describes the molecular targets aiming at developing the anti-AD agents including the inhibition of AChE, inhibition of Aβ production by enhancing α-secretase (non-amyloidogenic pathway) or inhibiting β- and γ-secretases (amyloidogenic pathway), alleviating Aβ-induced neurotoxicity or reducing Aβ-induced neuroinflammation. In addition, this paper summarizes the potential of some of the natural products that might inhibit specific molecular targets and slow the progression of this disease.

Key words

Alzheimer’s disease Therapeutics Natural products Beta-amyloid (Aβ) 

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References

  1. Abramov, A. Y., Canevari, L., and Duchen, M. R., Changes in intracellular calcium and glutathione in astrocytes as the primary mechanism of amyloid neurotoxicity. J. Neurosci., 23, 5088–5095 (2003).PubMedGoogle Scholar
  2. Ahmad, A., Khan, K. A., Ahmad, V. U., and Qazi, S., Antibacterial Activity of Juliflorine Isolated from Prosopis juliflora. Planta Med., 52, 285–288 (1986).PubMedCrossRefGoogle Scholar
  3. Anderson, J. J., Holtz, G., Baskin, P. P., Turner, M., Rowe, B., Wang, B., Kounnas, M. Z., Lamb, B. T., Barten, D., Felsenstein, K., McDonald, I., Srinivasan, K., Munoz, B., Wagner, S. L., Reductions in beta-amyloid concentrations in vivo by the gamma-secretase inhibitors BMS-289948 and BMS-299897. Biochem. Pharmacol., 69, 689–698 (2005).PubMedCrossRefGoogle Scholar
  4. Ansari, M. A. and Scheff, S. W., Oxidative stress in the progression of Alzheimer disease in the frontal cortex. J. Neuropathol. Exp. Neurol., 69, 155–167 (2010).PubMedCrossRefGoogle Scholar
  5. Barrow, C. J. and Zagorski, M. G., Solution structures of beta peptide and its constituent fragments: relation to amyloid deposition. Science, 253, 179–182 (1991).PubMedCrossRefGoogle Scholar
  6. Bastianetto, S., Ramassamy, C., Dore, S., Christen, Y., Poirier, J., and Quirion, R., The Ginkgo biloba extract (EGb 761) protects hippocampal neurons against cell death induced by beta-amyloid. Eur. J. Neurosci., 12, 1882–1890 (2000a).PubMedCrossRefGoogle Scholar
  7. Bastianetto, S., Zheng, W. H., and Quirion, R., Neuroprotective abilities of resveratrol and other red wine constituents against nitric oxide-related toxicity in cultured hippocampal neurons. Br. J. Pharmacol., 131, 711–720 (2000b).PubMedCrossRefGoogle Scholar
  8. Benzi, G. and Moretti, A., Are reactive oxygen species involved in Alzheimer’s disease? Neurobiol. Aging, 16, 661–674 (1995).PubMedCrossRefGoogle Scholar
  9. Block, M. L. and Hong, J. S., Microglia and inflammationmediated neurodegeneration: multiple triggers with a common mechanism. Prog. Neurobiol., 76, 77–98 (2005).PubMedCrossRefGoogle Scholar
  10. Block, M. L., Zecca, L., and Hong, J. S., Microglia-mediated neurotoxicity: uncovering the molecular mechanisms. Nat. Rev. Neurosci., 8, 57–69 (2007).PubMedCrossRefGoogle Scholar
  11. Blumenthal, M., Asian ginseng: potential therapeutic uses. Adv. Nurse Pract., 9, 26–28, 33 (2001).PubMedGoogle Scholar
  12. Borek, C., Garlic reduces dementia and heart-disease risk. J. Nutr., 136, 810S–812S (2006).PubMedGoogle Scholar
  13. Brinker, A. M., Ma, J., Lipsky, P. E., and Raskin, I., Medicinal chemistry and pharmacology of genus Tripterygium (Celastraceae). Phytochemistry, 68, 732–766 (2007).PubMedCrossRefGoogle Scholar
  14. Busciglio, J., Lorenzo, A., Yeh, J., and Yankner, B. A., betaamyloid fibrils induce tau phosphorylation and loss of microtubule binding. Neuron, 14, 879–888 (1995).PubMedCrossRefGoogle Scholar
  15. Cao, X. and Sudhof, T. C., Dissection of amyloid-beta precursor protein-dependent transcriptional transactivation. J. Biol. Chem., 279, 24601–24611 (2004).PubMedCrossRefGoogle Scholar
  16. Catalan, J., Moriguchi, T., Slotnick, B., Murthy, M., Greiner, R. S., and Salem, N., Jr., Cognitive deficits in docosahexaenoic acid-deficient rats. Behav. Neurosci., 116, 1022–1031 (2002).PubMedCrossRefGoogle Scholar
  17. Chang, Y. L., Shen, J. J., Wung, B. S., Cheng, J. J., and Wang, D. L., Chinese herbal remedy wogonin inhibits monocyte chemotactic protein-1 gene expression in human endothelial cells. Mol. Pharmacol., 60, 507–513 (2001).PubMedGoogle Scholar
  18. Chauhan, N. B., Effect of aged garlic extract on APP processing and tau phosphorylation in Alzheimer’s transgenic model Tg2576. J. Ethnopharmacol., 108, 385–394 (2006).PubMedCrossRefGoogle Scholar
  19. Chauhan, N. B. and Sandoval, J., Amelioration of early cognitive deficits by aged garlic extract in Alzheimer’s transgenic mice. Phytother. Res., 21, 629–640 (2007).PubMedCrossRefGoogle Scholar
  20. Choi, S. H., Hur, J. M., Yang, E. J., Jun, M., Park, H. J., Lee, K. B., Moon, E., and Song, K. S., Beta-secretase (BACE1) inhibitors from Perilla frutescens var. acuta. Arch. Pharm. Res., 31, 183–187 (2008a).PubMedCrossRefGoogle Scholar
  21. Choi, Y. H., Yon, G. H., Hong, K. S., Yoo, D. S., Choi, C. W., Park, W. K., Kong, J. Y., Kim, Y. S., and Ryu, S. Y., In vitro BACE-1 inhibitory phenolic components from the seeds of Psoralea corylifolia. Planta Med., 74, 1405–1408 (2008b).PubMedCrossRefGoogle Scholar
  22. Choi, Y. H., Yoo, M. Y., Choi, C. W., Cha, M. R., Yon, G. H., Kwon, D. Y., Kim, Y. S., Park, W. K., and Ryu, S. Y., A new specific BACE-1 inhibitor from the stembark extract of Vitis vinifera. Planta Med., 75, 537–540 (2009).PubMedCrossRefGoogle Scholar
  23. Chou, T. C., Anti-inflammatory and analgesic effects of paeonol in carrageenan-evoked thermal hyperalgesia. Br. J. Pharmacol., 139, 1146–1152 (2003).PubMedCrossRefGoogle Scholar
  24. Choudhary, M. I., Nawaz, S. A., ul-Haq, Z., Lodhi, M. A., Ghayur, M. N., Jalil, S., Riaz, N., Yousuf, S., Malik, A., Gilani, A. H., and ur-Rahman, A., Withanolides, a new class of natural cholinesterase inhibitors with calcium antagonistic properties. Biochem. Biophys. Res. Commun., 334, 276–287 (2005a).PubMedCrossRefGoogle Scholar
  25. Choudhary, M. I., Nawaz, S. A., Zaheerul, H., Azim, M. K., Ghayur, M. N., Lodhi, M. A., Jalil, S., Khalid, A., Ahmed, A., Rode, B. M., Attaur, R., Gilani, A. U., and Ahmad, V. U., Juliflorine: a potent natural peripheral anionic-sitebinding inhibitor of acetylcholinesterase with calciumchannel blocking potential, a leading candidate for Alzheimer’s disease therapy. Biochem. Biophys. Res. Commun., 332, 1171–1177 (2005b).PubMedCrossRefGoogle Scholar
  26. Colciaghi, F., Borroni, B., Zimmermann, M., Bellone, C., Longhi, A., Padovani, A., Cattabeni, F., Christen, Y., and Di Luca, M., Amyloid precursor protein metabolism is regulated toward alpha-secretase pathway by Ginkgo biloba extracts. Neurobiol. Dis., 16, 454–460 (2004).PubMedCrossRefGoogle Scholar
  27. Cummings, J. L., Vinters, H. V., Cole, G. M., and Khachaturian, Z. S., Alzheimer’s disease: etiologies, pathophysiology, cognitive reserve, and treatment opportunities. Neurology, 51, S2–17; discussion S65-17 (1998).PubMedGoogle Scholar
  28. Dinamarca, M. C., Cerpa, W., Garrido, J., Hancke, J. L., and Inestrosa, N. C., Hyperforin prevents beta-amyloid neurotoxicity and spatial memory impairments by disaggregation of Alzheimer’s amyloid-beta-deposits. Mol. Psychiatry, 11, 1032–1048 (2006).PubMedCrossRefGoogle Scholar
  29. Dovey, H. F., John, V., Anderson, J. P., Chen, L. Z., de Saint Andrieu, P., Fang, L. Y., Freedman, S. B., Folmer, B., Goldbach, E., Holsztynska, E. J., Hu, K. L., Johnson-Wood, K. L., Kennedy, S. L., Kholodenko, D., Knops, J. E., Latimer, L. H., Lee, M., Liao, Z., Lieberburg, I. M., Motter, R. N., Mutter, L. C., Nietz, J., Quinn, K. P., Sacchi, K. L., Seubert, P. A., Shopp, G. M., Thorsett, E. D., Tung, J. S., Wu, J., Yang, S., Yin, C. T., Schenk, D. B., May, P. C., Altstiel, L. D., Bender, M. H., Boggs, L. N., Britton, T. C., Clemens, J. C., Czilli, D. L., Dieckman-McGinty, D. K., Droste, J. J., Fuson, K. S., Gitter, B. D., Hyslop, P. A., Johnstone, E. M., Li, W. Y., Little, S. P., Mabry, T. E., Miller, F. D., and Audia, J. E., Functional gamma-secretase inhibitors reduce beta-amyloid peptide levels in brain. J. Neurochem., 76, 173–181 (2001).PubMedCrossRefGoogle Scholar
  30. Drew, P. D., Storer, P. D., Xu, J., and Chavis, J. A., Hormone regulation of microglial cell activation: relevance to multiple sclerosis. Brain Res. Brain Res. Rev., 48, 322–327 (2005).PubMedCrossRefGoogle Scholar
  31. Drieu, K., Preparation and definition of Ginkgo biloba extract. Presse Med., 15, 1455–1457 (1986).PubMedGoogle Scholar
  32. Durairajan, S. S., Yuan, Q., Xie, L., Chan, W. S., Kum, W. F., Koo, I., Liu, C., Song, Y., Huang, J. D., Klein, W. L., and Li, M., Salvianolic acid B inhibits Abeta fibril formation and disaggregates preformed fibrils and protects against Abeta-induced cytotoxicty. Neurochem. Int., 52, 741–750 (2008).PubMedCrossRefGoogle Scholar
  33. Esch, F. S., Keim, P. S., Beattie, E. C., Blacher, R. W., Culwell, A. R., Oltersdorf, T., McClure, D., and Ward, P. J., Cleavage of amyloid beta peptide during constitutive processing of its precursor. Science, 248, 1122–1124 (1990).PubMedCrossRefGoogle Scholar
  34. Ferris, S., Ihl, R., Robert, P., Winblad, B., Gatz, G., Tennigkeit, F., and Gauthier, S., Treatment effects of Memantine on language in moderate to severe Alzheimer’s disease patients. Alzheimers Dement., 5, 369–374 (2009).PubMedCrossRefGoogle Scholar
  35. Francis, P. T., Palmer, A. M., Snape, M., and Wilcock, G. K., The cholinergic hypothesis of Alzheimer’s disease: a review of progress. J. Neurol. Neurosurg. Psychiatr., 66, 137–147 (1999).PubMedCrossRefGoogle Scholar
  36. Fujiwara, H., Iwasaki, K., Furukawa, K., Seki, T., He, M., Maruyama, M., Tomita, N., Kudo, Y., Higuchi, M., Saido, T. C., Maeda, S., Takashima, A., Hara, M., Ohizumi, Y., and Arai, H., Uncaria rhynchophylla, a Chinese medicinal herb, has potent antiaggregation effects on Alzheimer’s beta-amyloid proteins. J. Neurosci. Res., 84, 427–433 (2006).PubMedCrossRefGoogle Scholar
  37. Fujiwara, H., Tabuchi, M., Yamaguchi, T., Iwasaki, K., Furukawa, K., Sekiguchi, K., Ikarashi, Y., Kudo, Y., Higuchi, M., Saido, T. C., Maeda, S., Takashima, A., Hara, M., Yaegashi, N., Kase, Y., and Arai, H., A traditional medicinal herb Paeonia suffruticosa and its active constituent 1,2,3,4,6-penta-O-galloyl-beta-D-glucopyranose have potent anti-aggregation effects on Alzheimer’s amyloid beta proteins in vitro and in vivo. J. Neurochem., 109, 1648–1657 (2009).PubMedCrossRefGoogle Scholar
  38. Ganguli, M., Chandra, V., Kamboh, M. I., Johnston, J. M., Dodge, H. H., Thelma, B. K., Juyal, R. C., Pandav, R., Belle, S. H., and DeKosky, S. T., Apolipoprotein E polymorphism and Alzheimer disease: The Indo-US Cross-National Dementia Study. Arch. Neurol., 57, 824–830 (2000).PubMedCrossRefGoogle Scholar
  39. Gao, Y. G., Song, Y. M., Yang, Y. Y., Liu, W. F., and Tang, J. X., [Pharmacology of tanshinone (author’s transl)]. Yao Xue Xue Bao, 14, 75–82 (1979).PubMedGoogle Scholar
  40. Giunta, B., Hou, H., Zhu, Y., Salemi, J., Ruscin, A., Shytle, R. D., and Tan, J., Fish oil enhances anti-amyloidogenic properties of green tea EGCG in Tg2576 mice. Neurosci. Lett., 471, 134–138 (2010).PubMedCrossRefGoogle Scholar
  41. Gong, Y., Xue, B., Jiao, J., Jing, L., and Wang, X., Triptolide inhibits COX-2 expression and PGE2 release by suppressing the activity of NF-kappaB and JNK in LPS-treated microglia. J. Neurochem., 107, 779–788 (2008).PubMedCrossRefGoogle Scholar
  42. Gonzalez-Scarano, F. and Baltuch, G., Microglia as mediators of inflammatory and degenerative diseases. Annu. Rev. Neurosci., 22, 219–240 (1999).PubMedCrossRefGoogle Scholar
  43. Greenberg, S. M. and Kosik, K. S., Secreted beta-APP stimulates MAP kinase and phosphorylation of tau in neurons. Neurobiol. Aging, 16, 403–407; discussion 407–408 (1995).PubMedCrossRefGoogle Scholar
  44. Gupta, V. B., Indi, S. S., and Rao, K. S., Garlic extract exhibits antiamyloidogenic activity on amyloid-beta fibrillogenesis: relevance to Alzheimer’s disease. Phytother. Res., 23, 111–115 (2009).PubMedCrossRefGoogle Scholar
  45. Hanisch, U. K., Microglia as a source and target of cytokines. Glia, 40, 140–155 (2002).PubMedCrossRefGoogle Scholar
  46. Hebert, L. E., Scherr, P. A., Bienias, J. L., Bennett, D. A., and Evans, D. A., Alzheimer disease in the US population: prevalence estimates using the 2000 census. Arch. Neurol., 60, 1119–1122 (2003).PubMedCrossRefGoogle Scholar
  47. Heneka, M. T. and O’Banion, M. K., Inflammatory processes in Alzheimer’s disease. J. Neuroimmunol., 184, 69–91 (2007).PubMedCrossRefGoogle Scholar
  48. Hsieh, L. T., Yang, H. H., and Chen, H. W., Ambient BTEX and MTBE in the neighborhoods of different industrial parks in Southern Taiwan. J. Hazard. Mater., 128, 106–115 (2006).PubMedCrossRefGoogle Scholar
  49. Ikemoto, A., Ohishi, M., Sato, Y., Hata, N., Misawa, Y., Fujii, Y., and Okuyama, H., Reversibility of n-3 fatty acid deficiency-induced alterations of learning behavior in the rat: level of n-6 fatty acids as another critical factor. J. Lipid Res., 42, 1655–1663 (2001).PubMedGoogle Scholar
  50. Iqbal, K., Liu, F., Gong, C. X., Alonso Adel, C., and Grundke-Iqbal, I., Mechanisms of tau-induced neurodegeneration. Acta Neuropathol., 118, 53–69 (2009).PubMedCrossRefGoogle Scholar
  51. Jeon, S. Y., Bae, K., Seong, Y. H., and Song, K. S., Green tea catechins as a BACE1 (beta-secretase) inhibitor. Bioorg. Med. Chem. Lett., 13, 3905–3908 (2003).PubMedCrossRefGoogle Scholar
  52. Jeon, S. Y., Kwon, S. H., Seong, Y. H., Bae, K., Hur, J. M., Lee, Y. Y., Suh, D. Y., and Song, K. S., Beta-secretase (BACE1)-inhibiting stilbenoids from Smilax Rhizoma. Phytomedicine, 14, 403–408 (2007).PubMedCrossRefGoogle Scholar
  53. Ji, Z. N., Dong, T. T., Ye, W. C., Choi, R. C., Lo, C. K., and Tsim, K. W., Ginsenoside Re attenuate beta-amyloid and serum-free induced neurotoxicity in PC12 cells. J. Ethnopharmacol., 107, 48–52 (2006).PubMedCrossRefGoogle Scholar
  54. Jia, H., Jiang, Y., Ruan, Y., Zhang, Y., Ma, X., Zhang, J., Beyreuther, K., Tu, P., and Zhang, D., Tenuigenin treatment decreases secretion of the Alzheimer’s disease amyloid beta-protein in cultured cells. Neurosci. Lett., 367, 123–128 (2004).PubMedCrossRefGoogle Scholar
  55. Jin, C. Y., Lee, J. D., Park, C., Choi, Y. H., and Kim, G. Y., Curcumin attenuates the release of pro-inflammatory cytokines in lipopolysaccharide-stimulated BV2 microglia. Acta Pharmacol. Sin., 28, 1645–1651 (2007).PubMedCrossRefGoogle Scholar
  56. Jung, H. A., Min, B. S., Yokozawa, T., Lee, J. H., Kim, Y. S., and Choi, J. S., Anti-Alzheimer and antioxidant activities of Coptidis Rhizoma alkaloids. Biol. Pharm. Bull., 32, 1433–1438 (2009).PubMedCrossRefGoogle Scholar
  57. Kalmijn, S., van Boxtel, M. P., Ocke, M., Verschuren, W. M., Kromhout, D., and Launer, L. J., Dietary intake of fatty acids and fish in relation to cognitive performance at middle age. Neurology, 62, 275–280 (2004).PubMedGoogle Scholar
  58. Kang, G., Kong, P. J., Yuh, Y. J., Lim, S. Y., Yim, S. V., Chun, W., and Kim, S. S., Curcumin suppresses lipopolysaccharideinduced cyclooxygenase-2 expression by inhibiting activator protein 1 and nuclear factor kappab bindings in BV2 microglial cells. J. Pharmacol. Sci., 94, 325–328 (2004).PubMedCrossRefGoogle Scholar
  59. Kelloff, G. J., Crowell, J. A., Steele, V. E., Lubet, R. A., Malone, W. A., Boone, C. W., Kopelovich, L., Hawk, E. T., Lieberman, R., Lawrence, J. A., Ali, I., Viner, J. L., and Sigman, C. C., Progress in cancer chemoprevention: development of diet-derived chemopreventive agents. J. Nutr., 130, 467S–471S (2000).PubMedGoogle Scholar
  60. Kim, D. H., Jeon, S. J., Jung, J. W., Lee, S., Yoon, B. H., Shin, B. Y., Son, K. H., Cheong, J. H., Kim, Y. S., Kang, S. S., Ko, K. H., and Ryu, J. H., Tanshinone congeners improve memory impairments induced by scopolamine on passive avoidance tasks in mice. Eur. J. Pharmacol., 574, 140–147 (2007).PubMedCrossRefGoogle Scholar
  61. Kim, H., Kim, Y. S., Kim, S. Y., and Suk, K., The plant flavonoid wogonin suppresses death of activated C6 rat glial cells by inhibiting nitric oxide production. Neurosci. Lett., 309, 67–71 (2001).PubMedCrossRefGoogle Scholar
  62. Kimura, Y., Matsushita, N., Yokoi-Hayashi, K., and Okuda, H., Effects of baicalein isolated from Scutellaria baicalensis Radix on adhesion molecule expression induced by thrombin and thrombin receptor agonist peptide in cultured human umbilical vein endothelial cells. Planta Med., 67, 331–334 (2001).PubMedCrossRefGoogle Scholar
  63. Klein, W. L., Krafft, G. A., and Finch, C. E., Targeting small Abeta oligomers: the solution to an Alzheimer’s disease conundrum? Trends Neurosci., 24, 219–224 (2001).PubMedCrossRefGoogle Scholar
  64. Kuboyama, T., Tohda, C., and Komatsu, K., Neuritic regeneration and synaptic reconstruction induced by withanolide A. Br. J. Pharmacol., 144, 961–971 (2005).PubMedCrossRefGoogle Scholar
  65. Lanz, T. A., Hosley, J. D., Adams, W. J., and Merchant, K. M., Studies of Abeta pharmacodynamics in the brain, cerebrospinal fluid, and plasma in young (plaque-free) Tg2576 mice using the gamma-secretase inhibitor N2-[(2S)-2-(3,5-difluorophenyl)-2-hydroxyethanoyl]-N1-[(7S)-5-methyl-6-oxo -6,7-dihydro-5H-dibenzo[b,d]azepin-7-yl]-L-alaninamide (LY-411575). J. Pharmacol. Exp. Ther., 309, 49–55 (2004).PubMedCrossRefGoogle Scholar
  66. Lee, H., Kim, Y. O., Kim, H., Kim, S. Y., Noh, H. S., Kang, S. S., Cho, G. J., Choi, W. S., and Suk, K., Flavonoid wogonin from medicinal herb is neuroprotective by inhibiting inflammatory activation of microglia. FASEB J., 17, 1943–1944 (2003).PubMedGoogle Scholar
  67. Lee, H. S., Jung, K. K., Cho, J. Y., Rhee, M. H., Hong, S., Kwon, M., Kim, S. H., and Kang, S. Y., Neuroprotective effect of curcumin is mainly mediated by blockade of microglial cell activation. Pharmazie, 62, 937–942 (2007).PubMedGoogle Scholar
  68. Lee, J. W., Lee, Y. K., Ban, J. O., Ha, T. Y., Yun, Y. P., Han, S. B., Oh, K. W., and Hong, J. T., Green tea (−)-epigallocatechin-3-gallate inhibits beta-amyloid-induced cognitive dysfunction through modification of secretase activity via inhibition of ERK and NF-kappaB pathways in mice. J. Nutr., 139, 1987–1993 (2009).PubMedCrossRefGoogle Scholar
  69. Lee, J. W., Lee, Y. K., Lee, B. J., Nam, S. Y., Lee, S. I., Kim, Y. H., Kim, K. H., Oh, K. W., and Hong, J. T., Inhibitory effect of ethanol extract of Magnolia officinalis and 4-Omethylhonokiol on memory impairment and neuronal toxicity induced by beta-amyloid. Pharmacol. Biochem. Behav., 95, 31–40 (2010).PubMedCrossRefGoogle Scholar
  70. Lesne, S. and Kotilinek, L., Amyloid plaques and amyloidbeta oligomers: an ongoing debate. J. Neurosci., 25, 9319–9320 (2005).PubMedCrossRefGoogle Scholar
  71. Letenneur, L., Dartigues, J. F., and Orgogozo, J. M., Wine consumption in the elderly. Ann. Intern. Med., 118, 317–318 (1993).PubMedGoogle Scholar
  72. Li, F. Q., Wang, T., Pei, Z., Liu, B., and Hong, J. S., Inhibition of microglial activation by the herbal flavonoid baicalein attenuates inflammation-mediated degeneration of dopaminergic neurons. J. Neural Transm., 112, 331–347 (2005).PubMedCrossRefGoogle Scholar
  73. Li, L., Tsai, H. J., and Wang, X. M., Icariin inhibits the increased inward calcium currents induced by amyloidbeta( 25–35) peptide in CA1 pyramidal neurons of neonatal rat hippocampal slice. Am. J. Chin. Med., 38, 113–125 (2010).PubMedCrossRefGoogle Scholar
  74. Li, N., Liu, B., Dluzen, D. E., and Jin, Y., Protective effects of ginsenoside Rg2 against glutamate-induced neurotoxicity in PC12 cells. J. Ethnopharmacol., 111, 458–463 (2007).PubMedCrossRefGoogle Scholar
  75. Li, Q., Zhao, H. F., Zhang, Z. F., Liu, Z. G., Pei, X. R., Wang, J. B., and Li, Y., Long-term green tea catechin administration prevents spatial learning and memory impairment in senescence-accelerated mouse prone-8 mice by decreasing Abeta1–42 oligomers and upregulating synaptic plasticity-related proteins in the hippocampus. Neuroscience, 163, 741–749 (2009).PubMedCrossRefGoogle Scholar
  76. Lim, G. P., Chu, T., Yang, F., Beech, W., Frautschy, S. A., and Cole, G. M., The curry spice curcumin reduces oxidative damage and amyloid pathology in an Alzheimer transgenic mouse. J. Neurosci., 21, 8370–8377 (2001).PubMedGoogle Scholar
  77. Lim, G. P., Calon, F., Morihara, T., Yang, F., Teter, B., Ubeda, O., Salem, N., Jr., Frautschy, S. A., and Cole, G. M., A diet enriched with the omega-3 fatty acid docosahexaenoic acid reduces amyloid burden in an aged Alzheimer mouse model. J. Neurosci., 25, 3032–3040 (2005).PubMedCrossRefGoogle Scholar
  78. Lim, J. Y., Won, T. J., Hwang, B. Y., Kim, H. R., Hwang, K. W., Sul, D., and Park, S. Y., The new diterpene isodojaponin D inhibited LPS-induced microglial activation through NF-kappaB and MAPK signaling pathways. Eur. J. Pharmacol., 642, 10–18 (2010).PubMedCrossRefGoogle Scholar
  79. Lin, H. C., Ding, H. Y., Ko, F. N., Teng, C. M., and Wu, Y. C., Aggregation inhibitory activity of minor acetophenones from Paeonia species. Planta Med., 65, 595–599 (1999).PubMedCrossRefGoogle Scholar
  80. Lin, L. C., Wang, M. N., Tseng, T. Y., Sung, J. S., and Tsai, T. H., Pharmacokinetics of (-)-epigallocatechin-3-gallate in conscious and freely moving rats and its brain regional distribution. J. Agric. Food Chem., 55, 1517–1524 (2007).PubMedCrossRefGoogle Scholar
  81. Lin, Y. H., Liu, A. H., Wu, H. L., Westenbroek, C., Song, Q. L., Yu, H. M., Ter Horst, G. J., and Li, X. J., Salvianolic acid B, an antioxidant from Salvia miltiorrhiza, prevents Abeta(25–35)-induced reduction in BPRP in PC12 cells. Biochem. Biophys. Res. Commun., 348, 593–599 (2006).PubMedCrossRefGoogle Scholar
  82. Lipton, S. A., Pathologically-activated therapeutics for neuroprotection: mechanism of NMDA receptor block by memantine and S-nitrosylation. Curr. Drug Targets, 8, 621–632 (2007).PubMedCrossRefGoogle Scholar
  83. Lleo, A., Greenberg, S. M., and Growdon, J. H., Current pharmacotherapy for Alzheimer’s disease. Annu. Rev. Med., 57, 513–533 (2006).PubMedCrossRefGoogle Scholar
  84. Lue, L. F., Kuo, Y. M., Roher, A. E., Brachova, L., Shen, Y., Sue, L., Beach, T., Kurth, J. H., Rydel, R. E., and Rogers, J., Soluble amyloid beta peptide concentration as a predictor of synaptic change in Alzheimer’s disease. Am. J. Pathol., 155, 853–862 (1999).PubMedGoogle Scholar
  85. Lv, J., Jia, H., Jiang, Y., Ruan, Y., Liu, Z., Yue, W., Beyreuther, K., Tu, P., and Zhang, D., Tenuifolin, an extract derived from tenuigenin, inhibits amyloid-beta secretion in vitro. Acta Physiol. (Oxf), 196, 419–425 (2009).CrossRefGoogle Scholar
  86. Marco, L. and do Carmo Carreiras, M., Galanthamine, a natural product for the treatment of Alzheimer’s disease. Recent Pat. CNS Drug Discov., 1, 105–111 (2006).PubMedCrossRefGoogle Scholar
  87. Marumoto, S. and Miyazawa, M., beta-secretase inhibitory effects of furanocoumarins from the root of Angelica dahurica. Phytother. Res., 24, 510–513 (2010).PubMedGoogle Scholar
  88. Mecocci, P., Bladstrom, A., and Stender, K., Effects of memantine on cognition in patients with moderate to severe Alzheimer’s disease: post-hoc analyses of ADAScog and SIB total and single-item scores from six randomized, double-blind, placebo-controlled studies. Int. J. Geriatr. Psychiatry, 24, 532–538 (2009).PubMedCrossRefGoogle Scholar
  89. Mei, Z., Zhang, F., Tao, L., Zheng, W., Cao, Y., Wang, Z., Tang, S., Le, K., Chen, S., Pi, R., and Liu, P., Cryptotanshinone, a compound from Salvia miltiorrhiza modulates amyloid precursor protein metabolism and attenuates beta-amyloid deposition through upregulating alphasecretase in vivo and in vitro. Neurosci. Lett., 452, 90–95 (2009).PubMedCrossRefGoogle Scholar
  90. Minghetti, L. and Levi, G., Microglia as effector cells in brain damage and repair: focus on prostanoids and nitric oxide. Prog. Neurobiol., 54, 99–125 (1998).PubMedCrossRefGoogle Scholar
  91. Montine, T. J., Neely, M. D., Quinn, J. F., Beal, M. F., Markesbery, W. R., Roberts, L. J., and Morrow, J. D., Lipid peroxidation in aging brain and Alzheimer’s disease. Free Radic. Biol. Med., 33, 620–626 (2002).PubMedCrossRefGoogle Scholar
  92. Morris, M. C., Evans, D. A., Bienias, J. L., Tangney, C. C., Bennett, D. A., Wilson, R. S., Aggarwal, N., and Schneider, J., Consumption of fish and n-3 fatty acids and risk of incident Alzheimer disease. Arch. Neurol., 60, 940–946 (2003).PubMedCrossRefGoogle Scholar
  93. Newman, D. J. and Cragg, G. M., Natural products as sources of new drugs over the last 25 years. J. Nat. Prod., 70, 461–477 (2007).PubMedCrossRefGoogle Scholar
  94. Nunan, J. and Small, D. H., Regulation of APP cleavage by alpha-, beta- and gamma-secretases. FEBS Lett., 483, 6–10 (2000).PubMedCrossRefGoogle Scholar
  95. Oberpichler, H., Beck, T., Abdel-Rahman, M. M., Bielenberg, G. W., and Krieglstein, J., Effects of Ginkgo biloba constituents related to protection against brain damage caused by hypoxia. Pharmacol. Res. Commun., 20, 349–368 (1988).PubMedCrossRefGoogle Scholar
  96. Ono, K., Hasegawa, K., Naiki, H., and Yamada, M., Antiamyloidogenic activity of tannic acid and its activity to destabilize Alzheimer’s beta-amyloid fibrils in vitro. Biochim. Biophys. Acta, 1690, 193–202 (2004a).PubMedGoogle Scholar
  97. Ono, K., Hasegawa, K., Naiki, H., and Yamada, M., Curcumin has potent anti-amyloidogenic effects for Alzheimer’s beta-amyloid fibrils in vitro. J. Neurosci. Res., 75, 742–750 (2004b).PubMedCrossRefGoogle Scholar
  98. Orgogozo, J. M., Dartigues, J. F., Lafont, S., Letenneur, L., Commenges, D., Salamon, R., Renaud, S., and Breteler, M. B., Wine consumption and dementia in the elderly: a prospective community study in the Bordeaux area. Rev. Neurol. (Paris), 153, 185–192 (1997).Google Scholar
  99. Ortega, M. G., Agnese, A. M., and Cabrera, J. L., Anticholinesterase activity in an alkaloid extract of Huperzia saururus. Phytomedicine, 11, 539–543 (2004).PubMedCrossRefGoogle Scholar
  100. Panegyres, P. K., The functions of the amyloid precursor protein gene. Rev. Neurosci., 12, 1–39 (2001).PubMedGoogle Scholar
  101. Park, B. K., Heo, M. Y., Park, H., and Kim, H. P., Inhibition of TPA-induced cyclooxygenase-2 expression and skin inflammation in mice by wogonin, a plant flavone from Scutellaria radix. Eur. J. Pharmacol., 425, 153–157 (2001).PubMedCrossRefGoogle Scholar
  102. Park, C. H., Choi, S. H., Koo, J. W., Seo, J. H., Kim, H. S., Jeong, S. J., and Suh, Y. H., Novel cognitive improving and neuroprotective activities of Polygala tenuifolia Willdenow extract, BT-11. J. Neurosci. Res., 70, 484–492 (2002).PubMedCrossRefGoogle Scholar
  103. Park, E. K., Choo, M. K., Oh, J. K., Ryu, J. H., and Kim, D. H., Ginsenoside Rh2 reduces ischemic brain injury in rats. Biol. Pharm. Bull., 27, 433–436 (2004).PubMedCrossRefGoogle Scholar
  104. Park, J. S., Park, E. M., Kim, D. H., Jung, K., Jung, J. S., Lee, E. J., Hyun, J. W., Kang, J. L., and Kim, H. S., Antiinflammatory mechanism of ginseng saponins in activated microglia. J. Neuroimmunol., 209, 40–49 (2009).PubMedCrossRefGoogle Scholar
  105. Park, S. Y., Kim, H. S., Cho, E. K., Kwon, B. Y., Phark, S., Hwang, K. W., and Sul, D., Curcumin protected PC12 cells against beta-amyloid-induced toxicity through the inhibition of oxidative damage and tau hyperphosphorylation. Food Chem. Toxicol., 46, 2881–2887 (2008).PubMedCrossRefGoogle Scholar
  106. Park, S. Y., Neuroprotective and neurotrophic effects of isorosmanol. Z. Naturforsch. C, 64, 395–398 (2009).PubMedGoogle Scholar
  107. Park, S. Y., Lim, J. Y., Jeong, W., Hong, S. S., Yang, Y. T., Hwang, B. Y., and Lee, D., C-methylflavonoids isolated from Callistemon lanceolatus protect PC12 cells against Abeta-induced toxicity. Planta Med., 76, 863–868 (2010).PubMedCrossRefGoogle Scholar
  108. Peng, Y., Xing, C., Lemere, C. A., Chen, G., Wang, L., Feng, Y., and Wang, X., l-3-n-Butylphthalide ameliorates betaamyloid-induced neuronal toxicity in cultured neuronal cells. Neurosci. Lett., 434, 224–229 (2008).PubMedCrossRefGoogle Scholar
  109. Peng, Y., Xing, C., Xu, S., Lemere, C. A., Chen, G., Liu, B., Wang, L., Feng, Y., and Wang, X., L-3-n-butylphthalide improves cognitive impairment induced by intracerebroventricular infusion of amyloid-beta peptide in rats. Eur. J. Pharmacol., 621, 38–45 (2009).PubMedCrossRefGoogle Scholar
  110. Peng, Y., Sun, J., Hon, S., Nylander, A. N., Xia, W., Feng, Y., Wang, X., and Lemere, C. A., L-3-n-butylphthalide improves cognitive impairment and reduces amyloid-beta in a transgenic model of Alzheimer’s disease. J. Neurosci., 30, 8180–8189 (2010).PubMedCrossRefGoogle Scholar
  111. Pike, C. J., Ramezan-Arab, N., and Cotman, C. W., Betaamyloid neurotoxicity in vitro: evidence of oxidative stress but not protection by antioxidants. J. Neurochem., 69, 1601–1611 (1997).PubMedCrossRefGoogle Scholar
  112. Qian, Y. H., Han, H., Hu, X. D., and Shi, L. L., Protective effect of ginsenoside Rb1 on beta-amyloid protein(1–42)-induced neurotoxicity in cortical neurons. Neurol. Res., 31, 663–667 (2009).PubMedCrossRefGoogle Scholar
  113. Qiu, D. and Kao, P. N., Immunosuppressive and anti-inflammatory mechanisms of triptolide, the principal active diterpenoid from the Chinese medicinal herb Tripterygium wilfordii Hook. f. Drugs R D, 4, 1–18 (2003).PubMedCrossRefGoogle Scholar
  114. Radad, K., Gille, G., Liu, L., and Rausch, W. D., Use of ginseng in medicine with emphasis on neurodegenerative disorders. J. Pharmacol. Sci., 100, 175–186 (2006).PubMedCrossRefGoogle Scholar
  115. Rai, G. S., Shovlin, C., and Wesnes, K. A., A double-blind, placebo controlled study of Ginkgo biloba extract (’tanakan’) in elderly outpatients with mild to moderate memory impairment. Curr. Med. Res. Opin., 12, 350–355 (1991).PubMedGoogle Scholar
  116. Rank, K. B., Pauley, A. M., Bhattacharya, K., Wang, Z., Evans, D. B., Fleck, T. J., Johnston, J. A., and Sharma, S. K., Direct interaction of soluble human recombinant tau protein with Abeta 1–42 results in tau aggregation and hyperphosphorylation by tau protein kinase II. FEBS Lett., 514, 263–268 (2002).PubMedCrossRefGoogle Scholar
  117. Rapoport, M., Dawson, H. N., Binder, L. I., Vitek, M. P., and Ferreira, A., Tau is essential to beta -amyloid-induced neurotoxicity. Proc. Natl. Acad. Sci. U.S.A., 99, 6364–6369 (2002).PubMedCrossRefGoogle Scholar
  118. Rezai-Zadeh, K., Shytle, D., Sun, N., Mori, T., Hou, H., Jeanniton, D., Ehrhart, J., Townsend, K., Zeng, J., Morgan, D., Hardy, J., Town, T., and Tan, J., Green tea epigallocatechin-3-gallate (EGCG) modulates amyloid precursor protein cleavage and reduces cerebral amyloidosis in Alzheimer transgenic mice. J. Neurosci., 25, 8807–8814 (2005).PubMedCrossRefGoogle Scholar
  119. Rezai-Zadeh, K., Arendash, G. W., Hou, H., Fernandez, F., Jensen, M., Runfeldt, M., Shytle, R. D., and Tan, J., Green tea epigallocatechin-3-gallate (EGCG) reduces betaamyloid mediated cognitive impairment and modulates tau pathology in Alzheimer transgenic mice. Brain Res., 1214, 177–187 (2008).PubMedCrossRefGoogle Scholar
  120. Roberson, E. D. and Mucke, L., 100 years and counting: prospects for defeating Alzheimer’s disease. Science, 314, 781–784 (2006).PubMedCrossRefGoogle Scholar
  121. Roberson, E. D., Scearce-Levie, K., Palop, J. J., Yan, F., Cheng, I. H., Wu, T., Gerstein, H., Yu, G. Q., and Mucke, L., Reducing endogenous tau ameliorates amyloid betainduced deficits in an Alzheimer’s disease mouse model. Science, 316, 750–754 (2007).PubMedCrossRefGoogle Scholar
  122. Rojo, L. E., Fernandez, J. A., Maccioni, A. A., Jimenez, J. M., and Maccioni, R. B., Neuroinflammation: implications for the pathogenesis and molecular diagnosis of Alzheimer’s disease. Arch. Med. Res., 39, 1–16 (2008).PubMedCrossRefGoogle Scholar
  123. Rosen, D. R., Martin-Morris, L., Luo, L. Q., and White, K., A Drosophila gene encoding a protein resembling the human beta-amyloid protein precursor. Proc. Natl. Acad. Sci. U.S.A., 86, 2478–2482 (1989).PubMedCrossRefGoogle Scholar
  124. Rovira, C., Arbez, N., and Mariani, J., Abeta(25–35) and Abeta(1–40) act on different calcium channels in CA1 hippocampal neurons. Biochem. Biophys. Res. Commun., 296, 1317–1321 (2002).PubMedCrossRefGoogle Scholar
  125. Rudakewich, M., Ba, F., and Benishin, C. G., Neurotrophic and neuroprotective actions of ginsenosides Rb(1) and Rg(1). Planta Med., 67, 533–537 (2001).PubMedCrossRefGoogle Scholar
  126. Selkoe, D. J., The cell biology of beta-amyloid precursor protein and presenilin in Alzheimer’s disease. Trends Cell Biol., 8, 447–453 (1998).PubMedCrossRefGoogle Scholar
  127. Selkoe, D. J., Alzheimer’s disease: genes, proteins, and therapy. Physiol. Rev., 81, 741–766 (2001).PubMedGoogle Scholar
  128. Selkoe, D. J., Alzheimer’s disease is a synaptic failure. Science, 298, 789–791 (2002).PubMedCrossRefGoogle Scholar
  129. Seubert, P., Oltersdorf, T., Lee, M. G., Barbour, R., Blomquist, C., Davis, D. L., Bryant, K., Fritz, L. C., Galasko, D., and Thal, L. J., Secretion of beta-amyloid precursor protein cleaved at the amino terminus of the beta-amyloid peptide. Nature, 361, 260–263 (1993).PubMedCrossRefGoogle Scholar
  130. Sha, D., Li, L., Ye, L., Liu, R., and Xu, Y., Icariin inhibits neurotoxicity of beta-amyloid by upregulating cocaine-regulated and amphetamine-regulated transcripts. Neuroreport, 20, 1564–1567 (2009).PubMedCrossRefGoogle Scholar
  131. Shi, C., Zhao, L., Zhu, B., Li, Q., Yew, D. T., Yao, Z., and Xu, J., Protective effects of Ginkgo biloba extract (EGb761) and its constituents quercetin and ginkgolide B against beta-amyloid peptide-induced toxicity in SH-SY5Y cells. Chem. Biol. Interact., 181, 115–123 (2009).PubMedCrossRefGoogle Scholar
  132. Shimada, Y., Goto, H., Itoh, T., Sakakibara, I., Kubo, M., Sasaki, H., and Terasawa, K., Evaluation of the protective effects of alkaloids isolated from the hooks and stems of Uncaria sinensis on glutamate-induced neuronal death in cultured cerebellar granule cells from rats. J. Pharm. Pharmacol., 51, 715–722 (1999).PubMedCrossRefGoogle Scholar
  133. Shytle, R. D., Bickford, P. C., Rezai-zadeh, K., Hou, L., Zeng, J., Tan, J., Sanberg, P. R., Sanberg, C. D., Roschek, B., Jr., Fink, R. C., and Alberte, R. S., Optimized turmeric extracts have potent anti-amyloidogenic effects. Curr. Alzheimer Res., 6, 564–571 (2009).PubMedCrossRefGoogle Scholar
  134. Smith, W. W., Gorospe, M., and Kusiak, J. W., Signaling mechanisms underlying Abeta toxicity: potential therapeutic targets for Alzheimer’s disease. CNS Neurol. Disord. Drug Targets, 5, 355–361 (2006).PubMedCrossRefGoogle Scholar
  135. Sonkusare, S. K., Kaul, C. L., and Ramarao, P., Dementia of Alzheimer’s disease and other neurodegenerative disorders-memantine, a new hope. Pharmacol. Res., 51, 1–17 (2005).PubMedGoogle Scholar
  136. Sramek, J. J., Frackiewicz, E. J., and Cutler, N. R., Review of the acetylcholinesterase inhibitor galanthamine. Expert Opin. Investig. Drugs, 9, 2393–2402 (2000).PubMedCrossRefGoogle Scholar
  137. Sreejayan and Rao, M. N., Nitric oxide scavenging by curcuminoids. J. Pharm. Pharmacol., 49, 105–107 (1997).PubMedGoogle Scholar
  138. St George-Hyslop, P. H. and Petit, A., Molecular biology and genetics of Alzheimer’s disease. C. R. Biol., 328, 119–130 (2005).PubMedCrossRefGoogle Scholar
  139. Suk, K., Lee, H., Kang, S. S., Cho, G. J., and Choi, W. S., Flavonoid baicalein attenuates activation-induced cell death of brain microglia. J. Pharmacol. Exp. Ther., 305, 638–645 (2003).PubMedCrossRefGoogle Scholar
  140. Szabo, M. E., Droy-Lefaix, M. T., and Doly, M., Direct measurement of free radicals in ischemic/reperfused diabetic rat retina. Clin. Neurosci., 4, 240–245 (1997).PubMedGoogle Scholar
  141. Takahashi, Y., Fuwa, H., Kaneko, A., Sasaki, M., Yokoshima, S., Koizumi, H., Takebe, T., Kan, T., Iwatsubo, T., Tomita, T., Natsugari, H., and Fukuyama, T., Novel gamma-secretase inhibitors discovered by library screening of in-house synthetic natural product intermediates. Bioorg. Med. Chem. Lett., 16, 3813–3816 (2006).PubMedCrossRefGoogle Scholar
  142. Takashima, A., Honda, T., Yasutake, K., Michel, G., Murayama, O., Murayama, M., Ishiguro, K., and Yamaguchi, H., Activation of tau protein kinase I/glycogen synthase kinase-3beta by amyloid beta peptide (25–35) enhances phosphorylation of tau in hippocampal neurons. Neurosci. Res., 31, 317–323 (1998).PubMedCrossRefGoogle Scholar
  143. Tanzi, R. E. and Bertram, L., Twenty years of the Alzheimer’s disease amyloid hypothesis: a genetic perspective. Cell, 120, 545–555 (2005).PubMedCrossRefGoogle Scholar
  144. Tian, J., Fu, F., Geng, M., Jiang, Y., Yang, J., Jiang, W., Wang, C., and Liu, K., Neuroprotective effect of 20(S)-ginsenoside Rg3 on cerebral ischemia in rats. Neurosci. Lett., 374, 92–97 (2005).PubMedCrossRefGoogle Scholar
  145. Tierney, M. C., Fisher, R. H., Lewis, A. J., Zorzitto, M. L., Snow, W. G., Reid, D. W., and Nieuwstraten, P., The NINCDS-ADRDA Work Group criteria for the clinical diagnosis of probable Alzheimer’s disease: a clinicopathologic study of 57 cases. Neurology, 38, 359–364 (1988).PubMedGoogle Scholar
  146. Um, M. Y., Ahn, J. Y., Kim, S., Kim, M. K., and Ha, T. Y., Sesaminol glucosides protect beta-amyloid peptide-induced cognitive deficits in mice. Biol. Pharm. Bull., 32, 1516–1520 (2009).PubMedCrossRefGoogle Scholar
  147. Van Marum, R. J., Current and future therapy in Alzheimer’s disease. Fundam. Clin. Pharmacol., 22, 265–274 (2008).PubMedCrossRefGoogle Scholar
  148. Virgili, M. and Contestabile, A., Partial neuroprotection of in vivo excitotoxic brain damage by chronic administration of the red wine antioxidant agent, trans-resveratrol in rats. Neurosci. Lett., 281, 123–126 (2000).PubMedCrossRefGoogle Scholar
  149. Wakabayashi, I., Inhibitory effects of baicalein and wogonin on lipopolysaccharide-induced nitric oxide production in macrophages. Pharmacol. Toxicol., 84, 288–291 (1999).PubMedCrossRefGoogle Scholar
  150. Wallin, A. K., Blennow, K., Andreasen, N., and Minthon, L., CSF biomarkers for Alzheimer’s Disease: levels of betaamyloid, tau, phosphorylated tau relate to clinical symptoms and survival. Dement. Geriatr. Cogn. Disord., 21, 131–138 (2006).PubMedCrossRefGoogle Scholar
  151. Walsh, D. M. and Selkoe, D. J., A beta oligomers — a decade of discovery. J. Neurochem., 101, 1172–1184 (2007).PubMedCrossRefGoogle Scholar
  152. Wang, L. C., Wang, B., Ng, S. Y., and Lee, T. F., Effects of ginseng saponins on beta-amyloid-induced amnesia in rats. J. Ethnopharmacol., 103, 103–108 (2006a).PubMedCrossRefGoogle Scholar
  153. Wang, R., Zhang, H. Y., and Tang, X. C., Huperzine A attenuates cognitive dysfunction and neuronal degeneration caused by beta-amyloid protein-(1–40) in rat. Eur. J. Pharmacol., 421, 149–156 (2001).PubMedCrossRefGoogle Scholar
  154. Wang, R., Yan, H., and Tang, X. C., Progress in studies of huperzine A, a natural cholinesterase inhibitor from Chinese herbal medicine. Acta Pharmacol. Sin., 27, 1–26 (2006b).PubMedCrossRefGoogle Scholar
  155. Wimo, A., Winblad, B., Aguero-Torres, H., and von Strauss, E., The magnitude of dementia occurrence in the world. Alzheimer Dis. Assoc. Disord., 17, 63–67 (2003).PubMedCrossRefGoogle Scholar
  156. Wirths, O., Multhaup, G., and Bayer, T. A., A modified betaamyloid hypothesis: intraneuronal accumulation of the beta-amyloid peptide—the first step of a fatal cascade. J. Neurochem., 91, 513–520 (2004).PubMedCrossRefGoogle Scholar
  157. Xiao, X. Q., Wang, R., Han, Y. F., and Tang, X. C., Protective effects of huperzine A on beta-amyloid (25–35) induced oxidative injury in rat pheochromocytoma cells. Neurosci. Lett., 286, 155–158 (2000).PubMedCrossRefGoogle Scholar
  158. Yan, H., Zhang, H. Y., and Tang, X. C., Involvement of M1-muscarinic acetylcholine receptors, protein kinase C and mitogen-activated protein kinase in the effect of huperzine A on secretory amyloid precursor protein-alpha. Neuroreport, 18, 689–692 (2007).PubMedCrossRefGoogle Scholar
  159. Yan, R., Bienkowski, M. J., Shuck, M. E., Miao, H., Tory, M. C., Pauley, A. M., Brashier, J. R., Stratman, N. C., Mathews, W. R., Buhl, A. E., Carter, D. B., Tomasselli, A. G., Parodi, L. A., Heinrikson, R. L., and Gurney, M. E., Membraneanchored aspartyl protease with Alzheimer’s disease betasecretase activity. Nature, 402, 533–537 (1999).PubMedCrossRefGoogle Scholar
  160. Yurko-Mauro, K., Cognitive and cardiovascular benefits of docosahexaenoic acid in aging and cognitive decline. Curr. Alzheimer Res., 7, 190–196 (2010).PubMedCrossRefGoogle Scholar
  161. Zaveri, N. T., Green tea and its polyphenolic catechins: medicinal uses in cancer and noncancer applications. Life Sci., 78, 2073–2080 (2006).PubMedCrossRefGoogle Scholar
  162. Zhang, D., Zhang, Y., Liu, G., and Zhang, J., Dactylorhin B reduces toxic effects of beta-amyloid fragment (25–35) on neuron cells and isolated rat brain mitochondria. Naunyn Schmiedebergs Arch. Pharmacol., 374, 117–125 (2006).PubMedCrossRefGoogle Scholar
  163. Zhang, J., Cheng, Y., and Zhang, J. T., Protective effect of (−) clausenamide against neurotoxicity induced by okadaic acid and beta-amyloid peptide25–35. Yao Xue Xue Bao, 42, 935–942 (2007).PubMedGoogle Scholar
  164. Zhao, B. L., Li, X. J., He, R. G., Cheng, S. J., and Xin, W. J., Scavenging effect of extracts of green tea and natural antioxidants on active oxygen radicals. Cell Biophys., 14, 175–185 (1989).PubMedGoogle Scholar
  165. Zheng, W. H., Bastianetto, S., Mennicken, F., Ma, W., and Kar, S., Amyloid beta peptide induces tau phosphorylation and loss of cholinergic neurons in rat primary septal cultures. Neuroscience, 115, 201–211 (2002).PubMedCrossRefGoogle Scholar
  166. Zhou, H. F., Liu, X. Y., Niu, D. B., Li, F. Q., He, Q. H., and Wang, X. M., Triptolide protects dopaminergic neurons from inflammation-mediated damage induced by lipopolysaccharide intranigral injection. Neurobiol. Dis., 18, 441–449 (2005).PubMedCrossRefGoogle Scholar
  167. Zipp, F. and Aktas, O., The brain as a target of inflammation: common pathways link inflammatory and neurodegenerative diseases. Trends Neurosci., 29, 518–527 (2006).PubMedCrossRefGoogle Scholar

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© The Pharmaceutical Society of Korea and Springer Netherlands 2010

Authors and Affiliations

  1. 1.Department of Nanobiomedical Science, College of Advanced ScienceDankook UniversityChungnamKorea

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