Abstract
Objective
To observe the effect of a Chinese medicine compound, Naoerkang (脑尔康, NEK), on amyloid-beta peptide (1–42; Aβ1–42) and matrix metalloproteinase-9 (MMP-9) expressions in the hippocampus of Alzheimer’s disease (AD) model rats.
Methods
A total of 48 male Sprague Dawley (SD) rats were randomly divided into normal control, untreated, and piracetam groups, and low-dose, medium-dose, and high-dose NEK groups, with 8 rats in each group. The 5-μL aggregated Aβ1–42 (2 μg/μL) were injected into both CA1 areas of the hippocampus in the rats to establish an AD model, whereas the normal control was treated with the same dose of normal saline. The rats in the NEK groups were treated with a high, medium, or low dose of NEK [60 g/(kg·d), 30 g/(kg·d), and 15 g/(kg·d)], respectively, intragastrically for 28 days; piracetam (0.375 g/kg, intragastrically) was consecutively administered in the piracetam group; and normal saline was applied in the normal control and untreated groups. A Y-maze test was used for behavioral study to test the learning and memory abilities. Aβ1–42 and MMP-9 expressions in the hippocampus was determined immunohistochemically, and the results were analyzed by image acquisition and an analysis system.
Results
Aggregated Aβ1–42 induced obvious learning and memory dysfunction, as well as up-regulation of Aβ1–42 expression in the hippocampus. Compared with those in the normal control group, the learning and memory abilities of rats in the untreated group significantly decreased (P<0.01), and the expression of Aβ1–42 was significantly increased (P<0.01). Twenty-eight days after different treatments, compared with those in the untreated group, the learning and memory abilities of AD model rats in the piracetam, low-dose, medium-dose and high-dose NEK groups were significantly improved (P<0.01 or P<0.05), and the expression of Aβ1–42 in the hippocampus decreased (P<0.01 or P<0.05), and MMP-9 increased (P<0.01 or P<0.05), especially in the high-dose NEK group.
Conclusion
NEK might play a role of anti-dementia by increasing the expression of MMP-9 in the hippocampus of AD model rats, resulting in the reduction of the quantity of Aβ1–42 and improvement in learning and memory ability in AD model rats.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Gallardo G, Schlüter OM, Südhof TC. A molecular pathway of neurodegeneration linking alpha-synuclein to ApoE and Abeta peptides. Nat Neurosci 2008;11:301–308.
Huang RX, Liang XL, Liu ZL. Clinical neurology. Beijing: People’s Medical Publishing House; 1998:505–506.
Yan P, Hu X, Song H, Yin K, Bateman RJ, Cirrito JR, et al. Matrix metalloproteinase-9 degrades amyloid-beta fibrils in vitro and compact plaques in situ. J Biol Chem 2006;281:24566–24574.
Selkoe DJ. Alzheimer’s disease: genes, proteins, and therapy. Physiol Rev 2001; 81:741–766.
Li X, Zhang XF, Qiao CL, Zhang ZY. Influence of Naoerkang on the intracerebral cholinesterase activity and neurons of mice with Alzheimer’s disease. Chin J Clin Rehabil (Chin) 2003;7:4222–4223.
Li X, Wang JJ, Qiao CL, Nie DL. Effects of Naoerkang on learning and memory dysfunction in mouse. J Xi’an Jiaotong Univ (Med Sci, Chin) 1999;20:126–127.
Bao XM, Shu SY. The rat brain in stereotaxic coordinates. Beijing: People’s Medical Publishing House; 1990:42.
Tian JZ, Xu Y, Shi J, Yin JX, Ji ZJ, Zhao ZW, et al. Effect of GETO extract on expression of growth-associated protein 43 in area CA1 of hippocampus in Alzheimer’s disease model rats induced by Aβ42 peptide. Chin J Integr Med Cardio-/Cerebrovas Dis (Chin) 2007;5:217–219.
Li QM, Meng RS, Wei CX, Kan FJ, Huang QH. Effects of Naohuandan recipe on learning and memory abilities of SAM-P/8 mice and its role in anti-oxidation and antiapoptosis. J Chin Integr Med (Chin) 2006;4:48–51.
Du GH. Experimental pharmacology. Beijing: Peking Union Medical College Press; 2004:33.
Yang P. Beta-amyloid peptide and Alzheimer’s disease. Med Recaptulate (Chin) 2001;7: 604–605.
Tanzi RE, Moir RD, Wagner SL. Clearance of Alzheimer’s A beta peptide: the many roads to perdition. Neuron 2004;43:605–608.
Yong VW, Krekoski CA, Forsyth PA, Bell R, Edwards DR. Matrix metalloproteinases and diseases of the CNS. Trends Neurosci 1998;21:75–80.
Van den Steen PE, Dubois B, Nelissen I, Rudd PM, Dwek RA, Opdenakker G. Biochemistry and molecular biology of gelatinase B or matrix metalloproteinase-9 (MMP-9). Crit Rev Biochem Mol Biol 2002;37:375–536.
Zhang JT. Nootropic mechanisms of ginsenoside Rg1-influence on neuronal plasticity and neurogenesis. Acta Pharm Sin (Chin) 2005;40:385–388.
Wang WX, Wang W, Chen KJ. Protective effect and mechanism of ginsenosides on central nerve system of animals. Chin J Integr Tradit West Med (Chin) 2005;25:89–93.
Shi RR, He LM, Hu YE, Weng SW, Cao YR, Yi NY. Regulation of milkvetch root on M-cholinergic receptors in the aged rats. J Tradit Chin Med (Chin) 1998;39:685–686.
Ji ZH, Yu XY, Zhang XL, Han H, Zhang W, Wang YF. Interventional effect of the water extract of Alpinia oxyphylla Miq. fruit on scopolamine-induced learning and memory impairements in rats. Chin J Clin Rehabi (Chin) 2005;8:120–122.
Yu ZL, Zhang GQ, Zhao HQ, Lu JF. Effect of puerariae isoflavone on memory in mice. J China Pharm Univ (Chin) 1997;28:350–353.
Zhang C, Wang SZ, Zuo PP, Cui X, Cai J. Effect of tetramethylpyrazine on learning,memory and cholinergic system in D-galactose-lesioned mice. Chin Acta Academiae Med Sinicae (Chin) 2003;25:553–556.
Cheng YM, Wang NY. Effect of borneol on the intercellular tight junction and pinocytosis vesicles in vitro bloodbrain barrier model. Chin J Integr Tradit West Med (Chin) 2004;24:632–634.
Author information
Authors and Affiliations
Additional information
Supported by Tackle Key Problems in-Science and Technology Foundation of Shaanxi Province [No.2007K16-07(5)]
Rights and permissions
About this article
Cite this article
Li, X., Yuan, Hf., Quan, Qk. et al. Scavenging effect of Naoerkang (脑尔康) on amyloid beta-peptide deposition in the hippocampus in a rat model of Alzheimer’s disease. Chin. J. Integr. Med. 17, 847–853 (2011). https://doi.org/10.1007/s11655-011-0896-7
Received:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11655-011-0896-7