Abstract
Objectives
To explore the protective effects of Tongmai Yizhi Decoction (通脉益智汤, TYD), a Chinese herb complex prescription against the impairment of cognitive functions and memory loss in amyloid beta 1–40 (Aβ1-40) peptide and ibotenic (IBO)-induced Alzheimer's disease (AD) model rats.
Methods
The in vivo model was established by injecting Aβ1-40 and IBO into left hippocampal CA1 area of Sprague-Dawley (SD) rat to mimic AD. Totally 32 SD rats were divided into 4 groups, including sham operation group, AD model group, TYD group [AD rats treated with TYD at the dosage of 19.44 g/(kg•d) for 4 weeks] and huperzine A group [AD rats treated with huperzine A at the dosage of 40.5 μg/(kg•d) for 4 weeks]. Spatial learning and memory level was detected by Morris Water Maze test. Histological morphology in the hippocampus was tested by hematoxylin-eosin (HE) staining. Cyclin-dependent kinase-5 (Cdk5) protein and gene expression level were investigated by Western blot analysis and real-time quantitative polymerase chain reaction (RT-qPCR), respectively.
Results
Aβ1-40 and IBO treatment induced longer escape latency of rats, compared with sham operation group from day 25 (P<0.01). However, TYD and huperzine A obviously shortened the escape latency from day 26 (P<0.01). Moreover, the effect of TYD was similar to huperzine A (P>0.05). Furthermore, HE staining also showed that TYD and huperzine A reversed the neuropathological changes in the hippocampus triggered by Aβ1-40 and IBO. TYD and huperzine A effectively reduced the expression levels of Cdk5 protein and gene located in rat hippocampus, compared with the AD model group (P<0.01).
Conclusion
TYD could be a promising neuroprotective agent for protecting neuron from AD injury through inhibiting Cdk5 expression.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Xie YL. Research progress of anti-dementia drugs. Pharmaceutical Clin Res (Chin) 2011;19:1–7.
Zhang J, Cicero SA, Wang L, Romito-Digiacomo RR, Yang Y, Herrup K. Nuclear localization of Cdk5 is a key determinant in the postmitotic state of neurons. Proc Natl Acad Sci USA 2008;105:8772–8777.
Cheung ZH, Ip NY. Cdk 5: amulti facetedk in ase in neurodegenerative diseases. Trends Cell Biol 2012;22:169–175.
Kanungo J, Zheng YL, Amin ND, Pant HC. Targeting Cdk5 activity in neuronal degeneration and regeneration. Cell Mol Neurobiol 2009;29:1073–1080.
Sundaram JR, Chan ES, Poore CP, Pareek TK, Cheong WF, Shui G, et al. Cdk5/p25-induced cytosolic PLA2-mediated lysophosphatidylcholine production regulates neuroinflammation and triggers neurodegeneration. J Neurosci 2012;32:1020–1034.
Chang KH, de Pablo Y, Lee HP, Lee HG, Smith MA, Shah K. Cdk5 is a major regulator of p38 cascade: relevance to neurotoxicity in Alzheimer's disease. J Neurochem 2010;113:1221–1229.
Wan Z. The role of tau protein hyperphosphorylation in the mechanism of Alzheimer's disease. Postgrad Med J 2010;23:539–542.
Hu H, Liao ZD. Phosphorylation and dephosphorylation of tau protein in Alzheimer's disease. Guangxi Med J (Chin) 2010;32:602–605.
Guo WF, Shan WB, Yuan Y, Wang GC. Clinic study: the effect of Tongmai Yizhi Capsule on the vascular dementia. J Nanjing Univ Chine Med (Chin) 2009;25:255–257.
Bian HM, Yu JH, Gong JN, Guo WF. Effect of Tongmai Yizhi Capsule (TYC) on memory of mouse. Chin J Herbal Pharmacol (Chin) 2000;16:40–42.
Guo WF, Shan WB, Wang GC. Effects of Tongmai Yizhi Capsule on the blood lipid and viscosity in vascular dementia patients. Liaoning J Tradit Chin Med (Chin) 2007;34:262–264.
Dai JG, Bian HM, Dai XM. Influence of Tongmai Yizhi formula on learning and memory behavior and synaptic structure of hippocampal CA1 sector of vascular dementia rats. Progress Modern Biomed (Chin) 2009;9:2044–2047.
Dai XM, Jiang FR, Bian HM, Chen L, Guo WF. Effect of Tongmai Yizhi Capsule on the structure of hippocampal CA1 sector of vascular dementia rats. J Southeast Univ (Med Sci ed, Chin) 2009;28:102–106.
The State Pharmacopoeia Commission of People's Republic of China. Pharmacopoeia of the People's Republic of China, Vol. I. Beijing: People's Medical Publishing House; 2010.
Su R, Han ZY, Fan JP. Discussion on pathogenesis of dementia from the role of Chinese medicine based on the theory of "brain damaged by the toxin". J Nanjing Univ Tradit Chin Med (Chin) 2010;26:93–94.
Zhang ZH, Kang JS, Ma YL. Significance of the role of collateral in revealing pathogenesis of dementia. Shanxi J Tradit Chin Med (Chin) 2010;31:327–329.
Zhang HY, Zheng CY, Yan H, Wang ZF, Tang LL, Gao X, et al. Potential therapeutic targets of huperzine A for Alzheimer's disease and vascular dementia. Chem Biol Interact 2008;175:396–402.
Ha GT, Wong RK, Zhang Y. Huperzine A as potential treatment of Alzheimer's disease: an assessment on chemistry, pharmacology, and clinical studies. Chem Biodivers 2011;8:1189–1204.
Ruan QW, Liu F, Gao ZJ, Kong D, Hu X, Shi D, et al. The antiinflamm-aging and hepatoprotective effects of huperzine A in D-galactose-treated rats. Mech Ageing Dev 2013;134:89–97.
Roselli F, Livrea P, Almeida OFX. Cdk5 is essential for soluble β-amyloid-induced degradation of GKAP and remodeling of the synaptic actin cytoskeleton. PloS One 2011;6:e23097.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Feng, Jh., Cai, Bc., Guo, Wf. et al. Neuroprotective effects of Tongmai Yizhi Decoction (通脉益智汤) against Alzheimer's disease through attenuating cyclin-dependent kinase-5 expression. Chin. J. Integr. Med. 23, 132–137 (2017). https://doi.org/10.1007/s11655-016-2507-0
Received:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11655-016-2507-0