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| Study on the intervention effect of Buyang Huanwu Decoction on APP/PS1 double transgenic mice based on metabolic network technology |
| WANG Baiyun1 YANG Liu2 LIU Guoliang2 PIAO Chengyu3 LI Qingwei2 XUE Hui2 LIU Bin2 |
1.Department of Pharmacy, Jinzhou Central Hospital, Liaoning Province, Jinzhou 121000, China;
2.Jiamusi College, Heilongjiang University of Chinese Medicine, Heilongjiang Province, Jiamusi 154007, China;
3.Center for Drug Safety Evaluation, Heilongjiang University of Chinese Medicine, Heilongjiang Province, Harbin 150040, China |
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Abstract Objective To reveal the regulation mechanism of Buyang Huanwu Decoction on APP/PS1 double transgenic mice based on metabolomics. Methods An animal model of Alzheimer′s disease was replicated in 20 APP/PS1 double transgenic mice. APP/PS1 double transgenic mice were randomly divided into two groups: model group and Buyang Huanwu Decoction group (9.26 g/kg). Ten healthy BALB/c mice were selected as control group. Buyang Huanwu Decoction group orally administrated with Buyang Huanwu Decoction, control group and model group were given the same volume of normal saline. Water maze behavior part tested the learning and memory ability of mice after 35 days′ intragastric administration. Then, the urine metabolites profiling analysis was conducted based on the high-throughput liquid chromatography mass spectrometry. The key metabolic enzymes or metabolic pathways in the course of disease development were traced by terminal metabolites, focusing on the pathogenesis of APP/PS1 double transgenic mice and the mechanism of Buyang Huanwu Decoction. Results In the Morris space exploration experiment, compared with the blank group, the number of platform crossing in the model group was significantly reduced (P < 0.05), the number of platform crossing in the Buyang Huanwu Decoction group was significantly increased (P < 0.05), and the residence time in the target quadrant was significantly increased (P < 0.05). In the space positioning navigation experiment, the escape latency of Buyang Huanwu Decoction group was significantly shorter than that of model group (P < 0.05). Through further analysis of urine metabolic trajectory, it was found that the urine of mice in each group was clustered well, and the separation between blank group and model group was obvious, while Buyang Huanwu Decoction group was located between the two groups. Through the contribution analysis of larger difference ion, it was found that lipid metabolism and lipid metabolism were mainly distributed in sphingolipids. The above metabolic pathways showed a significant callback trend after supplementing Buyang Huanwu Decoction. Four biomarkers with abnormal metabolism were identified by high resolution mass spectrometry. They were arachidonate acid, sphingosine, L-palmitoyl carnitine and glycerophosphocholine. Through online analysis of the metastadata data processing platform Metaboanalyst 4.0, it was known that it mainly involved two metabolic pathways, namely sphingolipid metabolism and arachidonic acid metabolism. Conclusion Buyang Huanwu Decoction has obvious effects on Alzheimer′s disease mice, which can effectively improve the learning and memory ability. Regulation of amino acid metabolism and energy conversion may be key mechanisms for its regulation of Alzheimer′s disease.
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