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Published in: BMC Complementary Medicine and Therapies 1/2014

Open Access 01-12-2014 | Research article

Compound danshen tablet ameliorated aβ25-35-induced spatial memory impairment in mice via rescuing imbalance between cytokines and neurotrophins

Authors: Yan Teng, Meng-Qi Zhang, Wen Wang, Li-Tao Liu, Li-Ming Zhou, Shi-Kun Miao, Li-Hong Wan

Published in: BMC Complementary Medicine and Therapies | Issue 1/2014

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Abstract

Background

Compound Danshen Tablet (CDT), a Traditional Chinese Medicine, has recently been reported to improve spatial cognition in a rat model of Alzheimer’s disease. However, in vivo neuroprotective mechanism of the CDT in models of spatial memory impairment is not yet evaluated. The present study is aimed to elucidate the cellular mechanism of CDT on Aβ25-35-induced cognitive impairment in mice.

Methods

Mice were randomly divided into 5 groups: the control group (sham operated), the Aβ25-35 treated group, the positive drug group, and large and small dosage of the CDT groups, respectively. CDT was administered at a dose of 0.81 g/kg and 0.405 g/kg for 3 weeks. The mice in the positive drug group were treated with 0.4 mg/kg of Huperzine A, whereas the mice of the control and Aβ25-35 treated groups were administrated orally with equivalent saline. After 7 days of preventive treatment, mice were subjected to lateral ventricle injection of Aβ25-35 to establish the mice model of Alzheimer’s disease. Spatial memory impairment was evaluated by Morris water maze test. Choline acetyltransferase (ChAT) contents in hippocampus and cortex were quantified by ELISA. The levels of cytokines, receptor of activated protein kinase C1 (RACK1) and brain-derived neurotrophic factor (BDNF) in hippocampus were measured by RT-PCR and ELISA.

Results

The results showed that Aβ25-35 caused spatial memory impairment as demonstrated by performance in the Morris water maze test. CDT was able to confer a significant improvement in spatial memory, and protect mice from Aβ25-35-induced neurotoxicity. Additionally, CDT also inhibited the increase of TNF-α and IL-6 level, and increased the expression of choline acetyltransferase (ChAT), receptor of activated protein kinase C1 (RACK1) and brain-derived neurotrophic factor (BDNF) in brain as compared to model mice.

Conclusion

These findings strongly implicate that CDT may be a useful treatment against learning and memory deficits in mice by rescuing imbalance between cytokines and neurotrophins.
Appendix
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Literature
1.
go back to reference Palmer AM: Pharmacotherapy for Alzheimer’s disease: progress and prospects. Trends Pharmacol Sci. 2002, 23 (9): 426-433. 10.1016/S0165-6147(02)02056-4.CrossRefPubMed Palmer AM: Pharmacotherapy for Alzheimer’s disease: progress and prospects. Trends Pharmacol Sci. 2002, 23 (9): 426-433. 10.1016/S0165-6147(02)02056-4.CrossRefPubMed
2.
go back to reference Selkoe DJ: Alzheimer’s disease is a synaptic failure. Science. 2002, 298 (5594): 789-791. 10.1126/science.1074069.CrossRefPubMed Selkoe DJ: Alzheimer’s disease is a synaptic failure. Science. 2002, 298 (5594): 789-791. 10.1126/science.1074069.CrossRefPubMed
3.
go back to reference Kang J, Rivest S: Lipid Metabolism and Neuroinflammation in Alzheimer’s Disease: A Role for Liver X Receptors. Endocr Rev. 2012, 33 (5): 715-746. 10.1210/er.2011-1049.CrossRefPubMed Kang J, Rivest S: Lipid Metabolism and Neuroinflammation in Alzheimer’s Disease: A Role for Liver X Receptors. Endocr Rev. 2012, 33 (5): 715-746. 10.1210/er.2011-1049.CrossRefPubMed
4.
go back to reference Puli L, Pomeshchik Y, Olas K, Malm T, Koistinaho J, Tanila H: Effects of human intravenous immunoglobulin on amyloid pathology and neuroinflammation in a mouse model of Alzheimer’s disease. J Neuroinflammation. 2012, 9: 105-10.1186/1742-2094-9-105.CrossRefPubMedPubMedCentral Puli L, Pomeshchik Y, Olas K, Malm T, Koistinaho J, Tanila H: Effects of human intravenous immunoglobulin on amyloid pathology and neuroinflammation in a mouse model of Alzheimer’s disease. J Neuroinflammation. 2012, 9: 105-10.1186/1742-2094-9-105.CrossRefPubMedPubMedCentral
5.
go back to reference Broussard GJ, Mytar J, Li RC, Klapstein GJ: The role of inflammatory processes in Alzheimer’s disease. Inflammopharmacology. 2012, 20 (3): 109-126. 10.1007/s10787-012-0130-z.CrossRefPubMed Broussard GJ, Mytar J, Li RC, Klapstein GJ: The role of inflammatory processes in Alzheimer’s disease. Inflammopharmacology. 2012, 20 (3): 109-126. 10.1007/s10787-012-0130-z.CrossRefPubMed
6.
go back to reference Peng S, Wuu J, Mufson EJ, Fahnestock M: Precursor form of brain-derived neurotrophic factor and mature brain-derived neurotrophic factor are decreased in the pre-clinical stages of Alzheimer’s disease. J Neurochem. 2005, 93 (6): 1412-1421. 10.1111/j.1471-4159.2005.03135.x.CrossRefPubMed Peng S, Wuu J, Mufson EJ, Fahnestock M: Precursor form of brain-derived neurotrophic factor and mature brain-derived neurotrophic factor are decreased in the pre-clinical stages of Alzheimer’s disease. J Neurochem. 2005, 93 (6): 1412-1421. 10.1111/j.1471-4159.2005.03135.x.CrossRefPubMed
7.
go back to reference Lu P, Mamiya T, Lu LL, Mouri A, Niwa M, Hiramatsu M, Zou LB, Nagai T, Ikejima T, Nabeshima T: Silibinin attenuates amyloid beta(25–35) peptide-induced memory impairments: implication of inducible nitric-oxide synthase and tumor necrosis factor-alpha in mice. J Pharmacol Exp Ther. 2009, 331 (1): 319-326. 10.1124/jpet.109.155069.CrossRefPubMed Lu P, Mamiya T, Lu LL, Mouri A, Niwa M, Hiramatsu M, Zou LB, Nagai T, Ikejima T, Nabeshima T: Silibinin attenuates amyloid beta(25–35) peptide-induced memory impairments: implication of inducible nitric-oxide synthase and tumor necrosis factor-alpha in mice. J Pharmacol Exp Ther. 2009, 331 (1): 319-326. 10.1124/jpet.109.155069.CrossRefPubMed
8.
go back to reference Xiao Q, Wang C, Li J, Hou Q, Li J, Ma J, Wang W, Wang Z: Ginkgolide B protects hippocampal neurons from apoptosis induced by beta-amyloid 25–35 partly via up-regulation of brain-derived neurotrophic factor. Eur J Pharmacol. 2010, 647 (1–3): 48-54.CrossRefPubMed Xiao Q, Wang C, Li J, Hou Q, Li J, Ma J, Wang W, Wang Z: Ginkgolide B protects hippocampal neurons from apoptosis induced by beta-amyloid 25–35 partly via up-regulation of brain-derived neurotrophic factor. Eur J Pharmacol. 2010, 647 (1–3): 48-54.CrossRefPubMed
9.
go back to reference Farlow MR, Cummings JL: Effective pharmacologic management of Alzheimer’s disease. Am J Med. 2007, 120 (5): 388-397. 10.1016/j.amjmed.2006.08.036.CrossRefPubMed Farlow MR, Cummings JL: Effective pharmacologic management of Alzheimer’s disease. Am J Med. 2007, 120 (5): 388-397. 10.1016/j.amjmed.2006.08.036.CrossRefPubMed
10.
go back to reference Danysz W, Parsons CG, Mobius HJ, Stoffler A, Quack G: Neuroprotective and symptomatological action of memantine relevant for Alzheimer’s disease–a unified glutamatergic hypothesis on the mechanism of action. Neurotox Res. 2000, 2 (2–3): 85-97.CrossRefPubMed Danysz W, Parsons CG, Mobius HJ, Stoffler A, Quack G: Neuroprotective and symptomatological action of memantine relevant for Alzheimer’s disease–a unified glutamatergic hypothesis on the mechanism of action. Neurotox Res. 2000, 2 (2–3): 85-97.CrossRefPubMed
11.
go back to reference Santos-Neto Dos LL, Vilhena Toledo de MA, Medeiros-Souza P, Souza de GA: The use of herbal medicine in Alzheimer’s disease-a systematic review. Evid Based Complement Alternat Med. 2006, 3 (4): 441-445. 10.1093/ecam/nel071.CrossRef Santos-Neto Dos LL, Vilhena Toledo de MA, Medeiros-Souza P, Souza de GA: The use of herbal medicine in Alzheimer’s disease-a systematic review. Evid Based Complement Alternat Med. 2006, 3 (4): 441-445. 10.1093/ecam/nel071.CrossRef
12.
go back to reference Iwasaki K, Satoh-Nakagawa T, Maruyama M, Monma Y, Nemoto M, Tomita N, Tanji H, Fujiwara H, Seki T, Fujii M, Arai H, Sasaki H: A randomized, observer-blind, controlled trial of the traditional Chinese medicine Yi-Gan San for improvement of behavioral and psychological symptoms and activities of daily living in dementia patients. J Clin Psychiatry. 2005, 66 (2): 248-252. 10.4088/JCP.v66n0214.CrossRefPubMed Iwasaki K, Satoh-Nakagawa T, Maruyama M, Monma Y, Nemoto M, Tomita N, Tanji H, Fujiwara H, Seki T, Fujii M, Arai H, Sasaki H: A randomized, observer-blind, controlled trial of the traditional Chinese medicine Yi-Gan San for improvement of behavioral and psychological symptoms and activities of daily living in dementia patients. J Clin Psychiatry. 2005, 66 (2): 248-252. 10.4088/JCP.v66n0214.CrossRefPubMed
13.
go back to reference Tohda C, Naito R, Joyashiki E: Kihi-to, a herbal traditional medicine, improves Abeta(25–35)-induced memory impairment and losses of neurites and synapses. BMC Complement Altern Med. 2008, 8: 49-10.1186/1472-6882-8-49.CrossRefPubMedPubMedCentral Tohda C, Naito R, Joyashiki E: Kihi-to, a herbal traditional medicine, improves Abeta(25–35)-induced memory impairment and losses of neurites and synapses. BMC Complement Altern Med. 2008, 8: 49-10.1186/1472-6882-8-49.CrossRefPubMedPubMedCentral
14.
go back to reference Qin RA, Yao XX, Huang ZY: Effects of compound danshen tablets on spatial cognition and expression of brain beta-amyloid precursor protein in a rat model of Alzheimer’s disease. J Tradit Chin Med. 2012, 32 (1): 63-66. 10.1016/S0254-6272(12)60033-8.CrossRefPubMed Qin RA, Yao XX, Huang ZY: Effects of compound danshen tablets on spatial cognition and expression of brain beta-amyloid precursor protein in a rat model of Alzheimer’s disease. J Tradit Chin Med. 2012, 32 (1): 63-66. 10.1016/S0254-6272(12)60033-8.CrossRefPubMed
15.
go back to reference Lee YW, Kim DH, Jeon SJ, Park SJ, Kim JM, Jung JM, Lee HE, Bae SG, Oh HK, Ho Son KH, Ryu JH:Neuroprotective effects of salvianolic acid B on an Aβ25-35peptide-induced mouse model of Alzheimer’s disease.Eur J Pharmacol. 2013, 704 (1–3): 70-77.CrossRefPubMed Lee YW, Kim DH, Jeon SJ, Park SJ, Kim JM, Jung JM, Lee HE, Bae SG, Oh HK, Ho Son KH, Ryu JH:Neuroprotective effects of salvianolic acid B on an Aβ25-35peptide-induced mouse model of Alzheimer’s disease.Eur J Pharmacol. 2013, 704 (1–3): 70-77.CrossRefPubMed
16.
go back to reference Yin Y, Huang L, Liu Y, Huang S, Zhuang J, Chen X, Zhang L, Wu H, Shao F, Zhao Z: Effect of tanshinone on the levels of nitric oxide synthase and acetylcholinesterase in the brain of Alzheimer’s disease rat model. Clin Invest Med. 2008, 31 (5): E248-E257.PubMed Yin Y, Huang L, Liu Y, Huang S, Zhuang J, Chen X, Zhang L, Wu H, Shao F, Zhao Z: Effect of tanshinone on the levels of nitric oxide synthase and acetylcholinesterase in the brain of Alzheimer’s disease rat model. Clin Invest Med. 2008, 31 (5): E248-E257.PubMed
17.
go back to reference Bai DL, Tang XC, He XC: Huperzine A, a potential therapeutic agent for treatment of Alzheimer’s disease. Curr Med Chem. 2000, 7 (3): 355-374. 10.2174/0929867003375281.CrossRefPubMed Bai DL, Tang XC, He XC: Huperzine A, a potential therapeutic agent for treatment of Alzheimer’s disease. Curr Med Chem. 2000, 7 (3): 355-374. 10.2174/0929867003375281.CrossRefPubMed
18.
go back to reference Huang L, Yao X-h, Lin Q, Xiao X-l: The Fingerprint of Compound Danshen Tablet (In Chinese). Research and Practice on Chinese Medicines. 2012, 26 (4): 66-69. Huang L, Yao X-h, Lin Q, Xiao X-l: The Fingerprint of Compound Danshen Tablet (In Chinese). Research and Practice on Chinese Medicines. 2012, 26 (4): 66-69.
19.
go back to reference Giovannelli L, Casamenti F, Scali C, Bartolini L, Pepeu G: Differential effects of amyloid peptides beta-(1–40) and beta-(25–35) injections into the rat nucleus basalis. Neuroscience. 1995, 66 (4): 781-792. 10.1016/0306-4522(94)00610-H.CrossRefPubMed Giovannelli L, Casamenti F, Scali C, Bartolini L, Pepeu G: Differential effects of amyloid peptides beta-(1–40) and beta-(25–35) injections into the rat nucleus basalis. Neuroscience. 1995, 66 (4): 781-792. 10.1016/0306-4522(94)00610-H.CrossRefPubMed
20.
go back to reference Diaz A, Limon D, Chávez R, Zenteno E, Guevara J: Aβ25-35 injection into the temporal cortex induces chronic inflammation that contributes to neurodegeneration and spatial memory impairment in rats. J Alzheimers Dis. 2012, 30 (3): 505-522.PubMed Diaz A, Limon D, Chávez R, Zenteno E, Guevara J: Aβ25-35 injection into the temporal cortex induces chronic inflammation that contributes to neurodegeneration and spatial memory impairment in rats. J Alzheimers Dis. 2012, 30 (3): 505-522.PubMed
21.
go back to reference Mori K, Obara Y, Moriya T, Inatomi S, Nakahata N: Effects of Hericium erinaceus on amyloid β(25–35) peptide-induced learning and memory deficits in mice. Biomed Res. 2011, 32 (1): 67-72. 10.2220/biomedres.32.67.CrossRefPubMed Mori K, Obara Y, Moriya T, Inatomi S, Nakahata N: Effects of Hericium erinaceus on amyloid β(25–35) peptide-induced learning and memory deficits in mice. Biomed Res. 2011, 32 (1): 67-72. 10.2220/biomedres.32.67.CrossRefPubMed
22.
go back to reference D'Hooge R, De Deyn PP: Applications of the Morris water maze in the study of learning and memory. Brain Res Brain Res Rev. 2001, 36 (1): 60-90. 10.1016/S0165-0173(01)00067-4.CrossRefPubMed D'Hooge R, De Deyn PP: Applications of the Morris water maze in the study of learning and memory. Brain Res Brain Res Rev. 2001, 36 (1): 60-90. 10.1016/S0165-0173(01)00067-4.CrossRefPubMed
23.
24.
go back to reference Ling FA, Hui DZ, Ji SM: Protective effect of recombinant human somatotropin on amyloid beta-peptide induced learning and memory deficits in mice. Growth Horm IGF Res. 2007, 17 (4): 336-341. 10.1016/j.ghir.2007.04.012.CrossRefPubMed Ling FA, Hui DZ, Ji SM: Protective effect of recombinant human somatotropin on amyloid beta-peptide induced learning and memory deficits in mice. Growth Horm IGF Res. 2007, 17 (4): 336-341. 10.1016/j.ghir.2007.04.012.CrossRefPubMed
25.
go back to reference Schliebs R, Arendt T: The significance of the cholinergic system in the brain during aging and in Alzheimer’s disease. J Neural Transm. 2006, 113 (11): 1625-1644. 10.1007/s00702-006-0579-2.CrossRefPubMed Schliebs R, Arendt T: The significance of the cholinergic system in the brain during aging and in Alzheimer’s disease. J Neural Transm. 2006, 113 (11): 1625-1644. 10.1007/s00702-006-0579-2.CrossRefPubMed
26.
go back to reference Ballard CG, Greig NH, Guillozet-Bongaarts AL, Enz A, Darvesh S: Cholinesterases: roles in the brain during health and disease. Curr Alzheimer Res. 2005, 2 (3): 307-318. 10.2174/1567205054367838.CrossRefPubMed Ballard CG, Greig NH, Guillozet-Bongaarts AL, Enz A, Darvesh S: Cholinesterases: roles in the brain during health and disease. Curr Alzheimer Res. 2005, 2 (3): 307-318. 10.2174/1567205054367838.CrossRefPubMed
27.
go back to reference Oda Y: Choline acetyltransferase: the structure, distribution and pathologic changes in the central nervous system. Pathol Int. 1999, 49 (11): 921-937. 10.1046/j.1440-1827.1999.00977.x.CrossRefPubMed Oda Y: Choline acetyltransferase: the structure, distribution and pathologic changes in the central nervous system. Pathol Int. 1999, 49 (11): 921-937. 10.1046/j.1440-1827.1999.00977.x.CrossRefPubMed
28.
go back to reference Combs CK, Karlo JC, Kao SC, Landreth GE: beta-Amyloid stimulation of microglia and monocytes results in TNFalpha-dependent expression of inducible nitric oxide synthase and neuronal apoptosis. J Neurosci. 2001, 21 (4): 1179-1188.PubMed Combs CK, Karlo JC, Kao SC, Landreth GE: beta-Amyloid stimulation of microglia and monocytes results in TNFalpha-dependent expression of inducible nitric oxide synthase and neuronal apoptosis. J Neurosci. 2001, 21 (4): 1179-1188.PubMed
29.
go back to reference Blasko I, Marx F, Steiner E, Hartmann T, Grubeck-Loebenstein B: TNFalpha plus IFNgamma induce the production of Alzheimer beta-amyloid peptides and decrease the secretion of APPs. FASEB J. 1999, 13 (1): 63-68.PubMed Blasko I, Marx F, Steiner E, Hartmann T, Grubeck-Loebenstein B: TNFalpha plus IFNgamma induce the production of Alzheimer beta-amyloid peptides and decrease the secretion of APPs. FASEB J. 1999, 13 (1): 63-68.PubMed
30.
go back to reference Spooren A, Kolmus K, Laureys G, Clinckers R, De Keyser J, Haegeman G, Gerlo S: Interleukin-6, a mental cytokine. Brain Res Rev. 2011, 67 (1–2): 157-183.CrossRefPubMed Spooren A, Kolmus K, Laureys G, Clinckers R, De Keyser J, Haegeman G, Gerlo S: Interleukin-6, a mental cytokine. Brain Res Rev. 2011, 67 (1–2): 157-183.CrossRefPubMed
31.
go back to reference Uslu S, Akarkarasu ZE, Ozbabalik D, Ozkan S, Colak O, Demirkan ES, Ozkiris A, Demirustu C, Alatas O: Levels of amyloid Beta-42, interleukin-6 and tumor necrosis factor-alpha in Alzheimer’s disease and vascular dementia. Neurochem Res. 2012, 37 (7): 1554-1559. 10.1007/s11064-012-0750-0.CrossRefPubMed Uslu S, Akarkarasu ZE, Ozbabalik D, Ozkan S, Colak O, Demirkan ES, Ozkiris A, Demirustu C, Alatas O: Levels of amyloid Beta-42, interleukin-6 and tumor necrosis factor-alpha in Alzheimer’s disease and vascular dementia. Neurochem Res. 2012, 37 (7): 1554-1559. 10.1007/s11064-012-0750-0.CrossRefPubMed
32.
go back to reference Van Eldik LJ, Thompson WL, Ralay Ranaivo H, Behanna HA, Martin Watterson D: Glia proinflammatory cytokine upregulation as a therapeutic target for neurodegenerative diseases: function-based and target-based discovery approaches. Int Rev Neurobiol. 2007, 82: 277-296.CrossRefPubMed Van Eldik LJ, Thompson WL, Ralay Ranaivo H, Behanna HA, Martin Watterson D: Glia proinflammatory cytokine upregulation as a therapeutic target for neurodegenerative diseases: function-based and target-based discovery approaches. Int Rev Neurobiol. 2007, 82: 277-296.CrossRefPubMed
33.
go back to reference Young AM, Campbell EC, Lynch S, Dunn MH, Powis SJ, Suckling J: Regional susceptibility to TNF-α induction of murine brain inflammation via classical IKK/NF-κB signalling. PLoS One. 2012, 7 (6): e39049-10.1371/journal.pone.0039049.CrossRefPubMedPubMedCentral Young AM, Campbell EC, Lynch S, Dunn MH, Powis SJ, Suckling J: Regional susceptibility to TNF-α induction of murine brain inflammation via classical IKK/NF-κB signalling. PLoS One. 2012, 7 (6): e39049-10.1371/journal.pone.0039049.CrossRefPubMedPubMedCentral
34.
go back to reference Song C, Zhang Y, Dong Y: Acute and subacute IL-1β administrations differentially modulate neuroimmune and neurotrophic systems: possible implications for neuroprotection and neurodegeneration. J Neuroinflammation. 2013, 10 (59): 31-32. Song C, Zhang Y, Dong Y: Acute and subacute IL-1β administrations differentially modulate neuroimmune and neurotrophic systems: possible implications for neuroprotection and neurodegeneration. J Neuroinflammation. 2013, 10 (59): 31-32.
35.
go back to reference Ji C, Song C, Zuo P: The mechanism of memory impairment induced by Aβ chronic administration involves imbalance between cytokines and neurotrophins in the rat hippocampus. Curr Alzheimer Res. 2011, 8 (4): 410-420. 10.2174/156720511795745366.CrossRefPubMed Ji C, Song C, Zuo P: The mechanism of memory impairment induced by Aβ chronic administration involves imbalance between cytokines and neurotrophins in the rat hippocampus. Curr Alzheimer Res. 2011, 8 (4): 410-420. 10.2174/156720511795745366.CrossRefPubMed
36.
go back to reference Battaini F, Pascale A: Protein kinase C signal transduction regulation in physiological and pathological aging. Ann N Y Acad Sci. 2005, 1057: 177-192. 10.1196/annals.1356.011.CrossRefPubMed Battaini F, Pascale A: Protein kinase C signal transduction regulation in physiological and pathological aging. Ann N Y Acad Sci. 2005, 1057: 177-192. 10.1196/annals.1356.011.CrossRefPubMed
37.
go back to reference He DY, Neasta J, Ron D: Epigenetic regulation of BDNF expression via the scaffolding protein RACK1. J Biol Chem. 2010, 285 (25): 19043-19050. 10.1074/jbc.M110.100693.CrossRefPubMedPubMedCentral He DY, Neasta J, Ron D: Epigenetic regulation of BDNF expression via the scaffolding protein RACK1. J Biol Chem. 2010, 285 (25): 19043-19050. 10.1074/jbc.M110.100693.CrossRefPubMedPubMedCentral
Metadata
Title
Compound danshen tablet ameliorated aβ25-35-induced spatial memory impairment in mice via rescuing imbalance between cytokines and neurotrophins
Authors
Yan Teng
Meng-Qi Zhang
Wen Wang
Li-Tao Liu
Li-Ming Zhou
Shi-Kun Miao
Li-Hong Wan
Publication date
01-12-2014
Publisher
BioMed Central
Published in
BMC Complementary Medicine and Therapies / Issue 1/2014
Electronic ISSN: 2662-7671
DOI
https://doi.org/10.1186/1472-6882-14-23

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