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[Biomarkers related to cognitive dysfunction in APP/PS1 mice based on non-targeted metabonomics and intervention mechanism of Huanglian Jiedu Decoction].

小桶 代谢组学 代谢途径 药理学 生物化学 脂肪酸代谢 轨道轨道 犬尿氨酸途径 化学 新陈代谢 生物 犬尿氨酸 氨基酸 生物信息学 色氨酸 质谱法 基因 色谱法 转录组 基因表达
作者
Linna Wang,Xinru Gu,Nan Si,Hongjie Wang,Yanyan Zhou,Baolin Bian,Haiyu Zhao
出处
期刊:PubMed 卷期号:47 (22): 6117-6126 被引量:2
标识
DOI:10.19540/j.cnki.cjcmm.20220705.401
摘要

Through the non-targeted metabonomics study on endogenous substances in APP/PS1 transgenic mice, this paper aimed to discover biomarkers related to APP/PS1 mice with cognitive dysfunction, and find targets of Huanglian Jiedu Decoction(HLJDD) in the treatment of Alzheimer's disease(AD) and its mechanism. The brain tissue and serum metabolic mass spectrometry of mice were analyzed by ultra-high performance liquid chromatography-Orbitrap mass spectrometry(UPLC-Orbitrap MS). Through partial least squares-discriminant analysis(PLS-DA) and orthogonal partial least squares-discriminant analysis(OPLS-DA), the metabolic data of the normal group, the model group, the high-dose and low-dose HLJDD groups, and the berberine group were compared and analyzed to screen out potential biomarkers, and the relevant metabolic pathways were constructed with the help of the Kyoto Encyclopedia of Genes and Genomes(KEGG) database. Forty-five potential endogenous metabolites were identified, including 13 in brain and 35 in serum, among which leukotriene B4, tyrosine, and adenosine were expected to be differential metabolites related to cognitive function. HLJDD recalled 22 differential metabolites, and the pathways mainly involved in aminoacyl-tRNA biosynthesis, valine, leucine and isoleucine biosynthesis, pantothenic acid and coenzyme A biosynthesis, phenylalanine, tyrosine and tryptophan biosynthesis, and arachidonic acid metabolism. These pathways suggested that the main mechanism of HLJDD in the intervention of AD was to inhibit central and peripheral inflammation, and regulate energy metabolism, fatty acid metabolism, and amino acid metabolism. HLJDD has a certain effect on the improvement of cognitive dysfunction, and regulates relative pathways by recalling endogenous differential metabolites, which helps to further discover the biomarkers of AD and clarify the intervention mechanism of HLJDD in the treatment of AD.
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