Neuroprotective Effects of Tongmai Yizhi Decoction against Alzheimer's Disease through Attenuating Cyclin-Dependent Kinase-5 Expression

Objectives: To explore the protective effects of Tongmai Yizhi Decoction (TYD), a Chinese herb complex prescription against the impairment of cognitive functions and memory loss in amyloid beta 1-40 (A beta(1-40)) peptide and ibotenic (IBO)-induced Alzheimer's disease (AD) model rats. Methods: The in vivo model was established by injecting A beta(1-40) 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 mu g/(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: A beta(1-40) 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 A beta(1-40) 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.