Gao Xianwei, Li Shengnan, Cong Chao, Wang Yuejiao, Xu Lianwei
Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China.
Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Evid Based Complement Alternat Med. 2021 Jan 28;2021:2302680. doi: 10.1155/2021/2302680. eCollection 2021.
The present study made use of a network pharmacological approach to evaluate the mechanisms and potential targets of the active ingredients of Epimedium for alleviating mild cognitive impairment (MCI) and treating Alzheimer's disease (AD).
The active ingredients of Epimedium were acquired from the Traditional Chinese Medicine System Pharmacology database, and potential targets were predicted using the TCMSP target module, SwissTargetPrediction, and PharmMapper database. Target proteins correlating with MCI and AD were downloaded from the GeneCards, DisGeNet, and OMIM databases. The common targets of Epimedium, MCI, and AD were identified using the Jvenn online tool, and a protein-protein interaction (PPI) network was constructed using the String database and Cytoscape. Finally, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of the common targets was performed using DAVID, and molecular docking between active ingredients and target genes was modeled using AutoDock Vina.
A total of 20 active ingredients were analyzed, and 337 compound-related targets were identified for Epimedium. Out of 236 proteins associated with MCI and AD, 54 overlapped with the targets of Epimedium. The top 30 interacting proteins in this set were ranked by topological analysis. GO and KEGG enrichment analysis suggested that the common targets participated in diverse biological processes and pathways, including cell proliferation and apoptosis, inflammatory response, signal transduction, and protein phosphorylation through cancer pathway, MAPK signaling pathway, PI3K-Akt signaling pathway, HIF-1 signaling pathway, sphingolipid signaling pathway, FoxO signaling pathway, and TNF signaling pathway. Molecular docking analysis suggested that the 20 active ingredients could bind to the top 5 protein targets.
The present study provides theoretical evidence for in-depth analysis of the mechanisms and molecular targets by which Epimedium protects against MCI, AD, and other neurodegenerative diseases and lays the foundation for pragmatic clinical applications and potential new drug development.
本研究采用网络药理学方法，评估淫羊藿活性成分缓解轻度认知障碍（MCI）和治疗阿尔茨海默病（AD）的机制及潜在靶点。
从中药系统药理学数据库获取淫羊藿的活性成分，利用TCMSP靶点模块、SwissTargetPrediction和PharmMapper数据库预测潜在靶点。从GeneCards、DisGeNet和OMIM数据库下载与MCI和AD相关的靶蛋白。使用Jvenn在线工具鉴定淫羊藿、MCI和AD的共同靶点，并使用String数据库和Cytoscape构建蛋白质-蛋白质相互作用（PPI）网络。最后，使用DAVID对共同靶点进行基因本体（GO）和京都基因与基因组百科全书（KEGG）富集分析，并使用AutoDock Vina对活性成分与靶基因之间进行分子对接建模。
共分析了20种活性成分，确定了337个与淫羊藿化合物相关的靶点。在与MCI和AD相关的236种蛋白质中，有54种与淫羊藿的靶点重叠。通过拓扑分析对该集合中前30个相互作用蛋白进行了排名。GO和KEGG富集分析表明，共同靶点参与了多种生物过程和途径，包括细胞增殖和凋亡、炎症反应、信号转导以及通过癌症途径、MAPK信号通路、PI3K-Akt信号通路、HIF-1信号通路、鞘脂信号通路、FoxO信号通路和TNF信号通路的蛋白质磷酸化。分子对接分析表明，20种活性成分可与前5个蛋白质靶点结合。
本研究为深入分析淫羊藿预防MCI、AD和其他神经退行性疾病的机制及分子靶点提供了理论依据，为实际临床应用和潜在新药开发奠定了基础。
