College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China (mainland).
Department of Chinese Pharmacy, School of Science, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China (mainland).
Med Sci Monit Basic Res. 2020 Jun 1;26:e924203. doi: 10.12659/MSMBR.924203.
BACKGROUND Acori Tatarinowii Rhizoma (ATR), a traditional Chinese herbal medicine, is used to treat Alzheimer's disease (AD), which is a worldwide degenerative brain disease. The aim of this study was to identify the potential mechanism and molecular targets of ATR in AD by using network pharmacology. MATERIAL AND METHODS The potential targets of the active ingredients of ATR were predicted by PharmMapper, and the targets of Alzheimer's disease were searched by DisGeNET. All screened genes were intersected to obtain potential targets for the active ingredients of ATR. The protein-protein interaction network of possible targets was established by STRING, GO Enrichment, and KEGG pathway enrichment analyses using the Annotation of DAVID database. Next, Cytoscape was used to build the "components-targets-pathways" networks. Additionally, a "disease-component-gene-pathways" network was constructed and verified by molecular docking methods. In addition, the active constituents ß-asarone and ß-caryophyllene were used to detect Aß₁₋₄₂-mediated SH-SY5Y cells, and mRNA expression levels of APP, Tau, and core target genes were estimated by qRT-PCR. RESULTS The results showed that the active components of ATR participate in related biological processes such as cancer, inflammation, cellular metabolism, and metabolic pathways and are closely related to the 13 predictive targets: ESR1, PPARG, AR, CASP3, JAK2, MAPK14, MAP2K1, ABL1, PTPN1, NR3C1, MET, INSR, and PRKACA. The ATR active components of ß-caryophyllene significantly reduced the mRNA expression levels of APP, TAU, ESR1, PTPN1, and JAK2. CONCLUSIONS The targets and mechanism corresponding to the active ingredients of ATR were investigated systematically, and novel ideas and directions were provided to further study the mechanism of ATR in AD.
石菖蒲（ATR）是一种传统的中药，用于治疗阿尔茨海默病（AD），这是一种全球性的退行性脑疾病。本研究旨在利用网络药理学方法鉴定 ATR 治疗 AD 的潜在机制和分子靶点。
通过 PharmMapper 预测 ATR 活性成分的潜在靶点，通过 DisGeNET 搜索阿尔茨海默病的靶点。所有筛选出的基因进行交集，获得 ATR 活性成分的潜在靶点。使用 STRING、GO 富集和 KEGG 通路富集分析数据库中的 DAVID 注释，构建可能靶点的蛋白质-蛋白质相互作用网络。接下来，使用 Cytoscape 构建“成分-靶点-通路”网络。此外，还通过分子对接方法构建和验证了“疾病-成分-基因-通路”网络。此外，使用活性成分ß-细辛脑和ß-石竹烯检测 Aß₁₋₄₂介导的 SH-SY5Y 细胞，通过 qRT-PCR 估计 APP、Tau 和核心靶基因的 mRNA 表达水平。
结果表明，ATR 的活性成分参与癌症、炎症、细胞代谢和代谢途径等相关生物过程，与 13 个预测靶点密切相关：ESR1、PPARG、AR、CASP3、JAK2、MAPK14、MAP2K1、ABL1、PTPN1、NR3C1、MET、INSR 和 PRKACA。ß-石竹烯的 ATR 活性成分显著降低了 APP、TAU、ESR1、PTPN1 和 JAK2 的 mRNA 表达水平。
系统研究了 ATR 活性成分的靶点和作用机制，为进一步研究 ATR 治疗 AD 的机制提供了新的思路和方向。
