Department of Neurology, The Third Affiliated Clinical Hospital of the Changchun University of Chinese Medicine, Changchun, Jilin Province, China.
Department of Neurology, People's Hospital of Linyi, Linyi, Shandong Province, China.
Metab Brain Dis. 2024 Nov 22;40(1):38. doi: 10.1007/s11011-024-01444-2.
This study aimed to investigate the mechanism of action of Jiedu Yizhi formula (JDYZF) in the treatment of Alzheimer's disease (AD) through network pharmacology, molecular docking technology, and in vivo experiments.
The main active ingredients of seven herbs in the Chinese Medicine compound JDYZF were identified by searching the TCMSP database, PubChem database, CNKI, and other sources. Disease targets of AD were obtained from databases such as OMIM, TDD, DisGeNET, and DrugBank. A protein‒protein interaction (PPI) network was constructed using the STRING platform, and core targets were identified through topological analysis using Cytoscape software. Gene Ontology (GO) functional analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of the relevant targets were performed using the Metascape database. The main active ingredients of JDYZF and potential core targets were identified based on degree values. Molecular docking technology was used to verify the interactions between the main active ingredients and potential core targets. Furthermore, water maze tests and hematoxylin-eosin (HE) staining of brain and liver tissues were performed to evaluate the effects of JDYZF on cognitive dysfunction in AD mice and neuronal damage in hippocampal brain tissue and to assess drug toxicity. PCR was performed to determine the expression levels of the apoptosis-related genes Bcl-2, Bax, and caspase-3 and to investigate the effect of JDYZF on hippocampal apoptosis in AD mice. Results. One hundred twelve core PPI target proteins, including CASP3, TP53, and VEGFA, were found between JDYZF and AD. The KEGG pathway enrichment analysis showed significant enrichment of the MAPK signaling pathway, PI3K/AKT signaling pathway and so on. Water maze tests revealed that the high-dose JDYZF treatment significantly improved the escape latency of AD model mice. The HE staining results showed that JDYZF exerted a protective effect on neuronal damage in the hippocampus of AD mice. JDYZF could upregulate the expression of the anti-apoptotic factor Bcl-2 while downregulating the expression of the proapoptotic factors Bax and caspase-3. Conclusion. JDYZF can improve the cognitive function of AD mice by suppressing cell apoptosis.
本研究旨在通过网络药理学、分子对接技术和体内实验探讨解毒益智方（JDYZF）治疗阿尔茨海默病（AD）的作用机制。
从 TCMSP 数据库、PubChem 数据库、CNKI 等数据库中检索中药复方 JDYZF 中七味药的主要活性成分，从 OMIM、TDD、DisGeNET、DrugBank 等数据库中获取 AD 疾病靶点，利用 STRING 平台构建蛋白质-蛋白质相互作用（PPI）网络，利用 Cytoscape 软件的拓扑分析识别核心靶点，利用 Metascape 数据库对相关靶点进行基因本体（GO）功能分析和京都基因与基因组百科全书（KEGG）通路富集分析。根据度值确定 JDYZF 的主要活性成分和潜在核心靶点，采用分子对接技术验证主要活性成分与潜在核心靶点的相互作用。此外，通过水迷宫试验和脑、肝组织的苏木精-伊红（HE）染色评估 JDYZF 对 AD 小鼠认知功能障碍和海马组织神经元损伤的影响，并评估药物毒性。采用 PCR 法测定凋亡相关基因 Bcl-2、Bax 和 caspase-3 的表达水平，探讨 JDYZF 对 AD 小鼠海马凋亡的影响。
发现 JDYZF 与 AD 之间存在 112 个核心 PPI 靶蛋白，包括 CASP3、TP53 和 VEGFA。KEGG 通路富集分析显示，MAPK 信号通路、PI3K/AKT 信号通路等显著富集。水迷宫试验显示，高剂量 JDYZF 治疗可显著缩短 AD 模型小鼠的逃避潜伏期。HE 染色结果表明，JDYZF 对 AD 小鼠海马神经元损伤具有保护作用。JDYZF 可上调抗凋亡因子 Bcl-2 的表达，下调促凋亡因子 Bax 和 caspase-3 的表达。
JDYZF 可通过抑制细胞凋亡改善 AD 小鼠的认知功能。
