ABSTRACT
Objective: To study the effect of Tonifying Spleen and Stomach Yuanqi Prescriptions including ginseng, Dabuyuan Decoction and Xixin Decoction on spatial learning and memory ability, hippocampal morphological function and cortical cholinergic system in rapidly aging dementia model mice (SAMP8), and investigate the possible mechanism on treating Alzheimer's disease. Methods: Male SAMP8 mice aged three months were randomly divided into model group, donepezil group, ginseng group, Xixin Decoction group and Dabuyuan Decoction group. Male anti-aging mice (SAMR1) were used as control group. In addition to control 3 months). The spatial learning and memory ability of mice was observed by Morris water maze test; The synaptic ultrastructure of hippocampal CA3 region was observed by transmission electron microscope; The density of neurons in CA1 area and the level of Aβ in brain tissue were detected by immunohistochemistry; The activities of choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) in hippocampus were detected by biochemical method. Results: The average escape latency of mice treated with Tonifying Spleen and Stomach Yuanqi Prescriptions was decreased, the swimming time and the number of passing through the platform were increased significantly (P < 0.05, 0.01). The number of Aβ positive cells were significantly decreased (P < 0.05, 0.01), the density of NueN positive cells had no significant difference. The level of CHAT activity was increased (P < 0.05, 0.01), and the level of AChE activity was decreased (P < 0.05). Conclusion: The effect of Tonifying Spleen and Stomach Yuanqi prescriptions improve the spatial recognition and learning and memory abilities in SAMP8 mice, of which mechanism may be related to affect the synaptic structure of hippocampus, promote the repair of hippocampal neurons, reduce the expression of Aβ in mouse brain, and regulate the cholinergic system in cortex.
ABSTRACT
Objective: To study the effects of prescriptions including Ginseng Decoction, Xixin Decoction, and Dabuyuan Decoction for tonifying spleen and stomach on learning and memory ability and PKA/ERK/p-CREB pathway in hippocampus of SAMP8 mice, and explore the mechanism in the prevention and treatment of Alzheimer's disease (AD). Methods: Three-month-old SAMP8 mice were randomly divided into model group, Donepezil Hydrochloride group, prescription group of Tonifying Spleen and Stomach Yuanqi Prescription (Ginseng, Xixin Decoction, and Dabuyuan Decoction). Moreover, three-month-old SAMR1 mice were recruited as a normal control group, six groups in total. Related indices were detected after 10 weeks continuous gastrogavage. The spatial learning-memory deficit of mice was detected by Morris water maze test. The expression levels of PKA protein in hippocampal region of mice were detected by immunohistochemistry, and the expression levels of ERK and p-CREB protein in hippocampal region of mice were detected by immunofluorescence. The protein expression levels of PKA, ERK, and p-CREB in hippocampus were detected by Western blotting. Results: Compared with the model group, the escape latency of the prescription group of tonifying spleen and stomach was decreased (P < 0.05, P < 0.01), while the swimming time and the times of crossing the platform in the target quadrant were increased (P < 0.01). Results of immunohistochemistry showed that the protein expression of PKA was significantly increased and the expression of ERK and p-CREB in hippocampal region was significantly increased (P < 0.05, P < 0.01). The results of Western blotting were consistent with those of immunohistochemistry and immunofluorescence (P < 0.05, P < 0.01). Conclusion: The Tonifying Spleen and Stomach Yuanqi Prescription showed obvious improvement on the spatial learning-memory deficit in SAMP8 mice, which might be associated with affecting the PKA/ERK/p-CREB pathway in hippocampal region.