Objective  To explore the protective effect and molecular mechanism of Rhodiola rosea tannin (RHTs), a traditional Chinese medicine, on cognitive impairment in APP/PS1 transgenic Alzheimer's disease (AD) mice.

Methods  A total of 48 APP/PS1 mice were randomly divided into the model group, high RHTs [150 mg/(kg·d)], medium RHTs [100  mg/(kg·d)], and low RHTs [50 mg/(kg·d)] dose groups, with 12 wild-type mice of the same age as the normal control group. Each dose group of RHTs was given a corresponding dose of RHTs daily for gastric lavage intervention, while the normal control group and model group were given an equal amount of physiological saline daily for continuous intervention for 4 weeks. After the intervention, the spatial learning and memory abilities of AD mice were evaluated using the Morris water maze experiment. HE staining was used to observe pathological changes in hippocampal tissue, immunofluorescence staining was used to detect the expression of Aβ_1-42 and p-Tau416 proteins in the hippocampus, and Western blot technology was used to detect the expression levels of phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt), mammalian rapamycin target protein (mTOR), p62, Beclin 1, and microtubule associated protein light chain 3 (LC3).

Results  Compared with the normal control group, the platform latency and swimming distance of the model group mice were significantly increased (P<0.05), and the number of platform crossings and target quadrant dwell time were significantly reduced (P<0.05); the arrangement of nerve cells in the hippocampal CA1 region was loose, and the nuclei were reduced in size and quantity; the fluorescence expression levels of Aβ_1-42 and p-Tau416 in the hippocampus were significantly increased (P<0.05); at the same time, the expression of p-PI3K, p-Akt, p-mTOR, and p62 proteins in hippocampal tissue was significantly upregulated, while the expression levels of Beclin 1 and LC3 were significantly decreased (P<0.05). After intervention with different doses of RHTs, all of the above metrics showed significant regression.

Conclusion  RHTs can improve cognitive impairment and neuronal pathological damage in APP/PS1 transgenic AD mice. The underlying molecular process may be associated to the interference with the PI3K/Akt/mTOR signaling pathway and the enhancement of cellular autophagy, which promotes the clearance of Aβ and phosphorylated Tau proteins. This study provides experimental ideas and theoretical basis for the screening of targets for the prevention and treatment of AD and promote the clinical development and application of the traditional Chinese medicine RHTs.

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