Erzhi pills ameliorate cognitive dysfunction and alter proteomic hippocampus profiles induced by d-galactose and Aβ1-40 injection in ovariectomized Alzheimer's disease model rats

二至丸改善卵巢切除阿尔茨海默病模型大鼠的认知功能障碍并改变 d-半乳糖和 Aβ1-40 注射引起的海马蛋白质组学特征

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作者:Yongyan Xie, Bo Yan, Min Hou, Maofu Zhou, Chao Liu, Mengsheng Sun, Kun He, Cong Fang, Yaohui Chen, Liping Huang

Conclusion

Erzhi pills may serve as a potential agent for AD therapeutics by improving learning and memory.

Methods

An AD rat model was established by ovariectomy combined with d-galactose and Aβ1-40 injection. Rats were randomly divided into five groups: sham-operated, model, oestradiol valerate (0.80 mg/kg), Erzhi pills high-dose (1.50 g/kg), and Erzhi pills low-dose (0.75 g/kg). Learning and memory abilities were evaluated with the Morris water maze test, oestrogen levels with an ELISA kit, and hippocampal neuron morphology and Nissl bodies in the cytoplasm with H&E and Nissl staining. The expression of ERβ, Aβ1-40, and p-tau404 was determined by immunohistochemistry. Nano LC-LTQ-Orbitrap Proteomics determined potential targets and related signalling pathways. Western blotting was used to detect the expression of the related proteins.

Objective

The protective effects of Erzhi pills in AD rats and their potential mechanisms were investigated. Materials and

Results

Erzhi pills (1.5, 0.75 g/kg) markedly reduced escape latencies on the MWM, increased numbers of platform crossings, numbers of neurons, Nissl bodies, oestrogen levels (100.18, 43.04 pg/mL), and ERβ-positive cells (57.42, 39.83); Aβ1-40 (18.85, 36.83)- and p-tau404 (14.42, 29.71)-positive cells were significantly decreased. Proteomics identified more than 100 differentially expressed proteins involved in 48 signalling pathways, five of which are involved in the PI3K/Akt signalling pathway. Western blotting showed decreased expression of GSK3β and Bad, while Akt, PI3K, 14-3-3, Bcl-xl, and Bcl-2 were upregulated.

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