多奈哌齐
药理学
莫里斯水上航行任务
神经保护
医学
活力测定
蛋氨酸
活性氧
化学
生物化学
内科学
海马体
细胞
痴呆
疾病
氨基酸
作者
Jung-Seop Kim,M. Kim,Ji Eun Ryu,Youngsub Lee,Quan Feng Liu,Kwang Ki Kim,Seung-Hun Cho,Sung Joon Shin,Byung Soo Koo,Hyo-Won Choi
标识
DOI:10.1016/j.jep.2023.117359
摘要
Woohwangchungsimwon (WCW) is a traditional medicine used in East Asian countries to treat central nervous system disorders. Reported pharmacological properties include antioxidant effects, enhanced learning and memory, and protection against ischemic neuronal cell death, supporting its use in treating neurodegenerative diseases like Alzheimer's disease (AD).The study aims to assess the effects of co-treatment with WCW and donepezil on cognitive functions and serum metabolic profiles in a scopolamine-induced AD model.Cell viability and reactive oxygen species (ROS) levels were measured in amyloid β-peptide25-35 (Aβ25-35)-induced SH-SY5Y cells. An AD model was established in ICR mice by intraperitoneal scopolamine administration. Animals underwent the step-through passive avoidance test (PAT) and Morris water maze (MWM) test. Hippocampal tissues were collected to examine specific protein expression. Serum metabolic profiles were analyzed using nuclear magnetic resonance (NMR) spectroscopy.Co-treatment with WCW and donepezil increased cell viability and reduced ROS production in Aβ25-35-induced SH-SY5Y cells compared to that with donepezil treatment alone. Co-treatment improved cognitive functions and was comparable to donepezil treatment alone in the PAT and MWM tests. Pathways related to tyrosine, phenylalanine, and tryptophan biosynthesis, phenylalanine metabolism, and cysteine and methionine metabolism were altered by co-treatment. Levels of tyrosine and methionine, major serum metabolites in these pathways, were significantly reduced after co-treatment.Co-treatment with WCW and donepezil shows promise as a therapeutic strategy for AD and is comparable to donepezil alone in improving cognitive function. Reduced tyrosine and methionine levels after co-treatment may enhance cognitive function by mitigating hypertyrosinemia and hyperhomocysteinemia, known risk factors for AD. The serum metabolic profiles obtained in this study can serve as a foundation for developing other bioactive compounds using a scopolamine-induced mouse model.
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