Tao Tian-Ze, Wang Lu, Liu Jie
School of Pharmacy, Guizhou University of Traditional Chinese Medicine, Guiyang, China.
National Engineering Research Center of Miao's Medicines, Guiyang, China.
Chem Biol Drug Des. 2023 Nov;102(5):1231-1247. doi: 10.1111/cbdd.14315. Epub 2023 Aug 10.
This study aimed to research the possible mechanism and effect of active ingredients of corn silk on Alzheimer's disease (AD) by the method of network pharmacology, molecular docking, and animal experiments. The active ingredients of Corn silk were obtained by searching the TCMSP database and the targets corresponding to the active ingredients of Corn silk were obtained through the TCMSP and SwissTargetPrediction platforms, and the AD targets were obtained in the GeneCards, OMIM, and DisgeNET databases. Cytoscape was employed for creating the "active ingredient-target" relationship network; STRING and Cytoscape for creating the protein-protein interaction (PPI) network. Besides, Meta scape was used for Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of the intersecting targets; AutoDockTools and Pymol for molecular docking and visualization of core ingredients and core targets; and animal experiments for verifying the anti-AD effect of luteolin. A total of 12 active ingredients of corn silk were screened, including 465 targets and 209 intersected targets. Moreover, GO functional analysis results showed that the anti-AD effect of corn silk was mainly reflected in phosphotransferase activity, response to hormone, membrane raft, etc.; KEGG results indicated the main pathways involving cancer, Alzheimer disease, etc.; and the molecular docking results revealed excellent binding of the core ingredients (α-tocopheryl quinone, luteolin, etc.) to the core targets. Besides, the outcomes of animal experiments exhibited that luteolin not only reduced the expression of inflammatory factors TNF-α and IL-1β in mice but also attenuated inflammation. With the help of network pharmacology and experimental validation, the material basis and mechanism of the anti-AD of corn silk have been explored in this study. Briefly speaking, luteolin from corn silk plays an anti-AD role by inhibiting inflammation.
本研究旨在通过网络药理学、分子对接和动物实验等方法,探讨玉米须活性成分对阿尔茨海默病(AD)的可能作用机制及效果。通过检索中药系统药理学数据库(TCMSP)获取玉米须的活性成分,并通过TCMSP和瑞士靶点预测平台获取玉米须活性成分对应的靶点,同时在基因卡片(GeneCards)、在线人类孟德尔遗传数据库(OMIM)和疾病基因数据库(DisgeNET)中获取AD靶点。利用Cytoscape软件构建“活性成分-靶点”关系网络;利用STRING和Cytoscape构建蛋白质-蛋白质相互作用(PPI)网络。此外,使用Metascape对交集靶点进行基因本体(GO)富集分析和京都基因与基因组百科全书(KEGG)通路富集分析;利用AutoDockTools和Pymol进行核心成分与核心靶点的分子对接及可视化;通过动物实验验证木犀草素的抗AD作用。共筛选出12种玉米须活性成分,包括465个靶点和209个交集靶点。此外,GO功能分析结果表明,玉米须的抗AD作用主要体现在磷酸转移酶活性、对激素的反应、膜筏等方面;KEGG结果表明主要涉及癌症、阿尔茨海默病等通路;分子对接结果显示核心成分(α-生育酚醌、木犀草素等)与核心靶点具有良好的结合。此外,动物实验结果表明,木犀草素不仅降低了小鼠体内炎症因子肿瘤坏死因子-α(TNF-α)和白细胞介素-1β(IL-1β)的表达,还减轻了炎症。本研究借助网络药理学和实验验证,探讨了玉米须抗AD的物质基础和作用机制。简而言之,玉米须中的木犀草素通过抑制炎症发挥抗AD作用。