LW-AFC, A New Formula Derived from Liuwei Dihuang Decoction, Ameliorates Cognitive Deterioration and Modulates Neuroendocrine-Immune System in SAMP8 Mouse

Page: [221 - 238] Pages: 18

  • * (Excluding Mailing and Handling)

Abstract

Background: Alzheimer’s disease (AD), the most common cause of dementia among older people, could not be prevented, halted, or reversed up till now. A large body of pharmacological study has revealed that Liuwei Dihuang decoction (LW), a classical traditional Chinese medicinal prescription, possesses potential therapeutic effects on AD. LW-AFC is key fractions from LW.

Method: Cognition ability was evaluated by behavioral experiments. Using multiplex bead analysis, radioimmunoassay, immunochemiluminometry and ELISA to determine levels of cytokines and hormones. The splenocyte proliferation and peripheral lymphocyte subsets was investigated by 3H-thymidine incorporation and flow cytometric analysis, respectively.

Results: This study showed the treatment of LW-AFC slowed the aging process of senescence-accelerated mouse prone 8 strain (SAMP8), a robust model sporadic AD or late-onset/age-related AD. LW-AFC had ameliorative effects on spontaneous locomotor activity, object recognition memory, spatial learning and memory, passive and active avoidance impairment in SAMP8 mice. Administration of LW-AFC restored the imbalance of hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-gonadal (HPG) axis, enhanced the proliferation of splenocytes, corrected the disorder of lymphocyte subsets, and regulated the abnormal production of cytokine in SAMP8 mice. Effects of LW-AFC on pharmacodynamics and neuroendocrine immunomodulation network in SAMP8 mice were better than memantine and donepezil.

Conclusion: This data indicated LW-AFC may be a promising therapeutic medicine for AD.

Keywords: LW-AFC, liuwei dihuang decoction, Alzheimer’s disease, senescence-accelerated mouse, prone 8 strain, cognitive behavior, neuroendocrine, splenocyte proliferation, lymphocyte subset, cytokine.

[1]
Ferri CP, Prince M, Brayne C, Brodaty H, Fratiglioni L, Ganguli M, et al. Global prevalence of dementia: a Delphi consensus study. Lancet 366(9503): 2112-7. (2005)
[2]
Citron M. Alzheimer’s disease: strategies for disease modification. Nat Rev Drug Discov 9(5): 387-98. (2010)
[3]
Courtney C, Farrell D, Gray R, Hills R, Lynch L, Sellwood E, et al. Long-term donepezil treatment in 565 patients with Alzheimer’s disease (AD2000): randomised double-blind trial. Lancet 363(9427): 2105-15. (2004)
[4]
Blacker D. Neither vitamin E nor donepezil delays progression from amnestic mild cognitive impairment to Alzheimer’s disease in the long term. Evid Based Ment Health 9(1): 20. (2006)
[5]
Dysken MW, Sano M, Asthana S, Vertrees JE, Pallaki M, Llorente M, et al. Effect of vitamin E and memantine on functional decline in Alzheimer disease: the TEAM-AD VA cooperative randomized trial. JAMA 311(1): 33-44. (2014)
[6]
Mangialasche F, Solomon A, Winblad B, Mecocci P, Kivipelto M. Alzheimer’s disease: clinical trials and drug development. Lancet Neurol 9(7): 702-16. (2010)
[7]
Bin Z, Chris G, Liviu-Gabriel B, Zhi W, Joshua ME, Podtelezhnikov AA, et al. Integrated systems approach identifies genetic nodes and networks in late-onset Alzheimer’s disease. Cell 153(3): 707-20. (2013)
[8]
Maccioni RB, Rojo LE, Fernandez JA, Kuljis RO. The role of neuroimmunomodulation in Alzheimer’s disease. Ann N Y Acad Sci 1153: 240-6. (2009)
[9]
Morales I, Farias G, Maccioni RB. Neuroimmunomodulation in the pathogenesis of Alzheimer’s disease. Neuroimmunomodulation 17(3): 202-4. (2010)
[10]
Xie X. LW-AFC Improved or restored the disturbance of reproductive endocrine and immune function in stress-loaded mice. Scientia Sin Vitae 41(10): 986. (2011)
[11]
Liu JP, Feng L, Zhang MH, Ma DY, Wang SY, Gu J, et al. Neuroprotective effect of Liuwei Dihuang decoction on cognition deficits of diabetic encephalopathy in streptozotocin-induced diabetic rat. J Ethnopharmacol 150(1): 371-81. (2013)
[12]
Park E, Kang M, Oh JW, Jung M, Park C, Cho C, et al. Yukmijihwang-tang derivatives enhance cognitive processing in normal young adults: a double-blinded, placebo-controlled trial. Am J Chin Med 33(1): 107-15. (2005)
[13]
Zhou J, Zhang Y, Zhou J. Cognition enhancing effect of liuwei dihuang decoction on age related deterioration of learning and memory in senescence accelerated Mouse (SAM). Chin J Exp Trad Med Formulae (1999)
[14]
Zhang WW, Sun QX, Liu YH, Gao W, Li YH, Lu K, et al. Chronic administration of Liu Wei Dihuang protects rat’s brain against D-galactose-induced impairment of cholinergic system. Acta Phys Sin 63(3): 245-55. (2011)
[15]
Hsieh MT, Cheng SJ, Lin LW, Wang WH, Wu CR. The ameliorating effects of acute and chronic administration of LiuWei Dihuang Wang on learning performance in rodents. Biol Pharm Bull 26(2): 156-61. (2003)
[16]
Wu CR, Lin LW, Wang WH, Hsieh MT. The ameliorating effects of LiuWei Dihuang Wang on cycloheximide-induced impairment of passive avoidance performance in rats. J Ethnopharmacol 113(1): 79-84. (2007)
[17]
Kang M, Kim JH, Cho C, Lee KY, Shin M, Hong M, et al. Effects of Yukmijihwang-tang derivatives (YMJd) on ibotenic acid-induced amnesia in the rat. Biol Pharm Bull 29(7): 1431-5. (2006)
[18]
Cheng XR, Zhou WX, Zhang YX. The behavioral, pathological and therapeutic features of the senescence-accelerated mouse prone 8 strain as an Alzheimer’s disease animal model. Ageing Res Rev 13: 13-37. (2014)
[19]
Hosokawa M, Kasai R, Higuchi K, Takeshita S, Shimizu K, Hamamoto H, et al. Grading score system: a method for evaluation of the degree of senescence in senescence accelerated mouse (SAM). Mech Ageing Dev 26(1): 91-102. (1984)
[20]
Cheng XR, Yang Y, Zhou WX, Zhang YX. Expression of VGLUTs contributes to degeneration and acquisition of learning and memory. Neurobiol Learn Mem 95(3): 361-75. (2011)
[21]
Bevins RA, Besheer J. Object recognition in rats and mice: a one-trial non-matching-to-sample learning task to study ‘recognition memory’. Nat Protoc 1(3): 1306-11. (2006)
[22]
Vorhees CV, Williams MT. Morris water maze: procedures for assessing spatial and related forms of learning and memory. Nat Protoc 1(2): 848-58. (2006)
[23]
He XL, Zhou WQ, Bi MG, Du GH. Neuroprotective effects of icariin on memory impairment and neurochemical deficits in senescence-accelerated mouse prone 8 (SAMP8) mice. Brain Res 1334: 73-83. (2010)
[24]
Lou G, Zhang Q, Xiao F, Xiang Q, Su Z, Zhang L, et al. Intranasal administration of TAT-haFGF((1)(4)(-)(1)(5)(4)) attenuates disease progression in a mouse model of Alzheimer’s disease. Neuroscience 223: 225-37. (2012)
[25]
Shi YQ, Huang TW, Chen LM, Pan XD, Zhang J, Zhu YG, et al. Ginsenoside Rg1 attenuates amyloid-beta content, regulates PKA/CREB activity, and improves cognitive performance in SAMP8 mice. J Alzheimers Dis 19(3): 977-89. (2010)
[26]
Bekris LM, Yu CE, Bird TD, Tsuang DW. Genetics of Alzheimer disease. J Geriatr Psychiatry Neurol 23(4): 213-27. (2010)
[27]
Alzheimer’s A. 2015 Alzheimer’s disease facts and figures. Alzheimers Dement 11(3): 332-84. (2015)
[28]
Dobarro M, Orejana L, Aguirre N, Ramirez MJ. Propranolol restores cognitive deficits and improves amyloid and Tau pathologies in a senescence-accelerated mouse model. Neuropharmacology 64: 137-44. (2013)
[29]
Lin N, Pan XD, Chen AQ, Zhu YG, Wu M, Zhang J, et al. Trip-chlorolide improves age-associated cognitive deficits by reversing hippocampal synaptic plasticity impairment and NMDA receptor dysfunction in SAMP8 mice. Behav Brain Res 258: 8-18. (2014)
[30]
Huang Y, Hu ZY, Yuan H, Shu L, Liu G, Qiao SY, et al. Danggui-Shaoyao-san improves learning and memory in female SAMP8 via modulation of estradiol. Evid-Based Comp Altern Med 2014327294 (2014)
[31]
Zhao L, Jia Y, Yan D, Zhou C, Han J, Yu J. Aging-related changes of triose phosphate isomerase in hippocampus of senescence accelerated mouse and the intervention of acupuncture. Neurosci Lett 542: 59-64. (2013)
[32]
Jia N, Han K, Kong J-J, Zhang X-M, Sha S, Ren G-R, et al. (-)-Epigallocatechin-3-gallate alleviates spatial memory impairment in APP/PS1 mice by restoring IRS-1 signaling defects in the hippocampus. Mol Cell Biochem 380(1-2): 211-8. (2013)
[33]
Goni F, Prelli F, Ji Y, Scholtzova H, Yang J, Sun Y, et al. Immunomodulation targeting abnormal protein conformation reduces pathology in a mouse model of Alzheimer’s disease. PLoS One 5(10)e13391 (2010)
[34]
Shih PH, Chan YC, Liao JW, Wang MF, Yen GC. Antioxidant and cognitive promotion effects of anthocyanin-rich mulberry (Morus atropurpurea L.) on senescence-accelerated mice and prevention of Alzheimer’s disease. J Nutr Biochem 21(7): 598-605. (2010)
[35]
Kapadia M, Sakic B. Autoimmune and inflammatory mechanisms of CNS damage. Prog Neurobiol 95(3): 301-33. (2011)
[36]
Masek K, Slansky J, Petrovicky P, Hadden JW. Neuroendocrine immune interactions in health and disease. Int Immunopharmacol 3(8): 1235-46. (2003)
[37]
Bilbo SD, Klein SL. Special Issue: the neuroendocrine-immune axis in health and disease. Horm Behav 62(3): 187-90. (2012)
[38]
Gimenez-Llort L, Arranz L, Mate I, De la Fuente M. Gender-specific neuroimmunoendocrine aging in a triple-transgenic 3xTg-AD mouse model for Alzheimer’s disease and its relation with longevity. Neuroimmunomodulation 15(4-6): 331-43. (2008)
[39]
Swanwick GR, Kirby M, Bruce I, Buggy F, Coen RF, Coakley D, et al. Hypothalamic-pituitary-adrenal axis dysfunction in Alzheimer’s disease: lack of association between longitudinal and cross-sectional findings. Am J Psychiatry 155(2): 286-9. (1998)
[40]
Hatzinger M, Z'Brun A, Hemmeter U, Seifritz E, Baumann F, Holsboer-Trachsler E, et al. Hypothalamic-pituitary-adrenal system function in patients with Alzheimer’s disease. Neurobiol Aging 16(2): 205-9. (1995)
[41]
McEwen BS. Central effects of stress hormones in health and disease: Understanding the protective and damaging effects of stress and stress mediators. Eur J Pharmacol 583(2-3): 174-85. (2008)
[42]
Verdile G, Laws SM, Henley D, Ames D, Bush AI, Ellis KA, et al. Associations between gonadotropins, testosterone and beta amyloid in men at risk of Alzheimer’s disease. Mol Psychiatry 19(1): 69-75. (2014)
[43]
Rosario ER, Carroll JC, Pike CJ. Evaluation of the effects of testosterone and luteinizing hormone on regulation of beta-amyloid in male 3xTg-AD mice. Brain Res 1466: 137-45. (2012)
[44]
Webber KM, Perry G, Smith MA, Casadesus G. The contribution of luteinizing hormone to Alzheimer disease pathogenesis. Clin Med Res 5(3): 177-83. (2007)
[45]
Bao AM, Hestiantoro A, Van Someren EJ, Swaab DF, Zhou JN. Colocalization of corticotropin-releasing hormone and oestrogen receptor-alpha in the paraventricular nucleus of the hypothalamus in mood disorders. Brain 128(Pt 6): 1301-13. (2005)
[46]
Flood JF, Farr SA, Kaiser FE, La Regina M, Morley JE. Age-related decrease of plasma testosterone in SAMP8 mice: replacement improves age-related impairment of learning and memory. Physiol Behav 57(4): 669-73. (1995)
[47]
Bernstein LR, Mackenzie ACL, Kraemer DC, Morley JE, Farr S, Chaffin CL, et al. Shortened estrous cycle length, increased FSH levels, FSH variance, oocyte spindle aberrations, and early declining fertility in aging senescence-accelerated mouse prone-8 (SAMP8) mice: concomitant characteristics of human midlife female reproductive aging. Endocrinology 155(6): 2287-300. (2014)
[48]
Ma Y, Zhou W-X, Cheng J-P, Zhang Y-X. Age-related changes in the oestrous cycle and reproductive hormones in senescence-accelerated mouse (vol 17, pg 507, 2005). Reprod Fertil Dev 21(4): 624-U133. (2009)
[49]
Yuan M, Wen-Xia Z, Jun-Ping C, Yong-Xiang Z. Age-related changes in the oestrous cycle and reproductive hormones in senescence-accelerated mouse. Reprod Fertil Dev 7(5): 507-12. (2005)
[50]
Warren MP, Perlroth NE. The effects of intense exercise on the female reproductive system. J Endocrinol 170(1): 3-11. (2001)
[51]
Guzeloglu A, Ambrose JD, Kassa T, Diaz T, Thatcher MJ, Thatcher WW. Long-term follicular dynamics and biochemical characteristics of dominant follicles in dairy cows subjected to acute heat stress. Ani Rep Sci 66(1-2): 15-34. (2001)
[52]
Gao HB, Tong MH, Hu YQ, Guo QS, Ge R, Hardy MP. Glucocorticoid induces apoptosis in rat leydig cells. Endocrinology 143(1): 130-8. (2002)
[53]
Melaragno MI, Smith MDA, Kormann-Bortolotto MH, Toniolo Neto JT. Lymphocyte proliferation and sister chromatid exchange in Alzheimer’s disease. Gerontology 37(6): 293-8. (1991)
[54]
Song C, Vandewoude M, Stevens W, De Clerck L, Van der Planken M, Whelan A, et al. Alterations in immune functions during normal aging and Alzheimer’s disease. Psychiatry Res 85(1): 71-80. (1999)
[55]
Araga S, Kagimoto H, Funamoto K, Takahashi K. Lymphocyte proliferation and subpopulations in dementia of the Alzheimer type. JAP J Med 29(6): 572-5. (1990)
[56]
Jozwik A, Landowski J, Bidzan L, Fuelop T, Bryl E, Witkowski JM. Beta-Amyloid Peptides Enhance the Proliferative Response of Activated CD4(+)CD28(+) Lymphocytes from Alzheimer Disease Patients and from Healthy Elderly. PLoS One 7(3) (2012)
[57]
Larbi A, Pawelec G, Witkowski JM, Schipper HM, Derhovanessian E, Goldeck D, et al. Dramatic shifts in circulating CD4 but not CD8 t cell subsets in mild Alzheimer’s Disease. J Alzheimers Dis 17(1): 91-103. (2009)
[58]
Lombardi VRM, Garcia M, Rey L, Cacabelos R. Characterization of cytokine production, screening of lymphocyte subset patterns and in vitro apoptosis in healthy and Alzheimer’s Disease (AD) individuals. J Neuroimmunol 97(1-2): 163-71. (1999)
[59]
Pellicano M, Larbi A, Goldeck D, Colonna-Romano G, Buffa S, Bulati M, et al. Immune profiling of Alzheimer patients. J Neuroimmunol 242(1-2): 52-9. (2012)
[60]
Speciale L, Calabrese E, Saresella M, Tinelli C, Mariani C, Sanvito L, et al. Lymphocyte subset patterns and cytokine production in Alzheimer’s disease patients. Neurobiol Aging 28(8): 1163-9. (2007)
[61]
Lueg G, Gross CC, Lohmann H, Johnen A, Kemmling A, Deppe M, et al. Clinical relevance of specific T-cell activation in the blood and cerebrospinal fluid of patients with mild Alzheimer’s disease. Neurobiol Aging 36(1): 81-9. (2015)
[62]
Pirttila T, Mattinen S, Frey H. The decrease of CD8-positive lymphocytes in Alzheimer’s disease. J Neurol Sci 107(2): 160-5. (1992)
[63]
Richartz-Salzburger E, Batra A, Stransky E, Laske C, Koehler N, Bartels M, et al. Altered lymphocyte distribution in Alzheimer’s disease. J Psychiatr Res 41(1-2): 174-8. (2007)
[64]
Shalit F, Sredni B, Brodie C, Kott E, Huberman M. T-Lymphocyte subpopulations and activation markers correlate with severity of Alzheimers-disease. Clin Immunol Immunopathol 75(3): 246-50. (1995)
[65]
May JE, Pemberton RM, Hart JP, McLeod J, Wilcock G, Doran O. Use of whole blood for analysis of disease-associated biomarkers. Anal Biochem 437(1): 59-61. (2013)
[66]
Saresella M, Calabrese E, Marventano I, Piancone F, Gatti A, Calvo MG, et al. PD1 negative and PD1 positive CD4+T regulatory cells in mild cognitive impairment and Alzheimer’s disease. J Alzheimers Dis 21(3): 927-38. (2010)
[67]
Schindowski K, Kratzsch T, Peters J, Steiner B, Leutner S, Touchet N, et al. Impact of aging. Neuromol Med 4(3): 161-77. (2003)
[68]
Huang Y, Hu Z, Liu G, Zhou W, Zhang Y. Cytokines induced by long-term potentiation (Ltp) recording: a potential explanation for the lack of correspondence between learning/memory performance and Ltp. Neuroscience 231: 432-43. (2013)
[69]
Liu FJ, Zhang YX, Lau BHS. Pycnogenol enhances immune and haemopoietic functions in senescence-accelerated mice. Cell Mol Life Sci 54(10): 1168-72. (1998)
[70]
Abe Y, Yuasa M, Kajiwara Y, Hosono M. Defects of immune cells in the senescence-accelerated mouse: A model for learning and memory deficits in the aged. Cell Immunol 157(1): 59-69. (1994)
[71]
Guo SJ, Qi CH, Zhou WX, Zhang YX, Zhang XM, Wang J, et al. Proteomic data show an increase in autoantibodies and alpha-fetoprotein and a decrease in apolipoprotein A-II with time in sera from senescence-accelerated mice. Braz J Med Biol Res 46(5): 417-25. (2013)
[72]
Luo Y, Li Y, Lin C, Ma H, Zhang J, Wu S, et al. Comparative proteome analysis of splenic lymphocytes in senescence-accelerated mice. Gerontology 55(5): 559-69. (2009)
[73]
Valentine AD, Meyers CA. Neurobehavioral effects of interferon therapy. Curr Psychiatry Rep 7(5): 391-5. (2005)
[74]
McAfoose J, Baune BT. Evidence for a cytokine model of cognitive function. Neurosci Biobehav Rev 33(3): 355-66. (2009)
[75]
Murray CA, Lynch MA. Evidence that increased hippocampal expression of the cytokine interleukin-1 beta is a common trigger for age- and stress-induced impairments in long-term potentiation. J Neurosci 18(8): 2974-81. (1998)
[76]
Cunningham AJ, Murray CA, O’Neill LA, Lynch MA, O’Connor JJ. Interleukin-1 beta (IL-1 beta) and tumour necrosis factor (TNF) inhibit long-term potentiation in the rat dentate gyrus in vitro. Neurosci Lett 203(1): 17-20. (1996)
[77]
Brennan FX, Beck KD, Servatius RJ. Low doses of interleukin-1beta improve the leverpress avoidance performance of Sprague-Dawley rats. Neurobiol Learn Mem 80(2): 168-71. (2003)
[78]
Capuron L, Ravaud A, Dantzer R. Timing and specificity of the cognitive changes induced by interleukin-2 and interferon-alpha treatments in cancer patients. Psychosom Med 63(3): 376-86. (2001)
[79]
Tan M-S, Yu J-T, Jiang T, Zhu X-C, Guan H-S, Tan L. IL12/23 p40 inhibition ameliorates Alzheimer’s disease-associated neuropathology and spatial memory in SAMP8 Mice. J Alzheimers Dis 38(3): 633-46. (2014)
[80]
Vom Berg J, Prokop S, Miller KR, Obst J, Kalin RE, Lopategui-Cabezas I, et al. Inhibition of IL-12/IL-23 signaling reduces Alzheimer’s disease-like pathology and cognitive decline. Nat Med 18(12): 1812-9. (2012)
[81]
Cao C, Arendash GW, Dickson A, Mamcarz MB, Lin X, Ethell DW. Abeta-specific Th2 cells provide cognitive and pathological benefits to Alzheimer’s mice without infiltrating the CNS. Neurobiol Dis 34(1): 63-70. (2009)
[82]
Baron R, Nemirovsky A, Harpaz I, Cohen H, Owens T, Monsonego A. IFN-gamma enhances neurogenesis in wild-type mice and in a mouse model of Alzheimer’s disease. FASEB J 22(8): 2843-52. (2008)
[83]
Fiore M, Angelucci F, Alleva E, Branchi I, Probert L, Aloe L. Learning performances, brain NGF distribution and NPY levels in transgenic mice expressing TNF-alpha. Behav Brain Res 112(1-2): 165-75. (2000)
[84]
Capsoni S, Cattaneo A. On the molecular basis linking Nerve Growth Factor (NGF) to Alzheimer’s disease. Cell Mol Neurobiol 26(4-6): 619-33. (2006)
[85]
Kiyota T, Yamamoto M, Schroder B, Jacobsen MT, Swan RJ, Lambert MP, et al. AAV1/2-mediated CNS gene delivery of dominant-negative CCL2 mutant suppresses gliosis, beta-amyloidosis, and learning impairment of APP/PS1 mice. Mol Ther 17(5): 803-9. (2009)
[86]
Villeda SA, Luo J, Mosher KI, Zou B, Britschgi M, Bieri G, et al. The ageing systemic milieu negatively regulates neurogenesis and cognitive function. Nature 477(7362): 90-4. (2011)
[87]
Tripathy D, Thirumangalakudi L, Grammas P. RANTES upregulation in the Alzheimer’s disease brain: a possible neuroprotective role. Neurobiol Aging 31(1): 8-16. (2010)
[88]
Nomura Y, Okuma Y, Hosoi T, Nomura J. Biochemical changes in the brain of the senescence-accelerated mouse P8 and P10. Int Congr Ser 1260: 91-7. (2004)
[89]
Rodriguez MI, Escames G, Lopez LC, Lopez A, Garcia JA, Ortiz F, et al. Chronic melatonin treatment reduces the age-dependent inflammatory process in senescence-accelerated mice. J Pineal Res 42(3): 272-9. (2007)
[90]
Cuesta S, Kireev R, Garcia C, Forman K, Escames G, Vara E, et al. Beneficial effect of melatonin treatment on inflammation, apoptosis and oxidative stress on pancreas of a senescence accelerated mice model. Mech Ageing Dev 132(11-12): 573-82. (2011)
[91]
Cuesta S, Kireev R, Garcia C, Forman K, Vara E, Tresguerres JAF. Effect of growth hormone treatment on pancreatic inflammation, oxidative stress, and apoptosis related to aging in SAMP8 mice. Rejuven Res 14(5): 501-12. (2011)