基于网络药理学方法探讨丹皮酚原苷改善 阿尔茨海默病的作用机制

Mechanism of Paeonolide in Improving Alzheimer’s Disease Based on Network Pharmacology

摘要: 目的：在网络药理学基础上探讨丹皮酚原苷(Paeonolide)改善阿尔茨海默病(Alzheimer’s disease, AD)的作用机制。方法：利用TargetNET、SwissTargetPrediction、SuperPRED数据库筛选Paeonolide的作用靶点，通过整合Genecard、OMIM和TTD数据库的方法挖掘AD的相关靶点，将Paeonolide的作用靶点与AD靶点通过Venny网站获取Paeonolide作用于AD的潜在靶点，应用STRING数据库构建蛋白质互作网络分析(PPI)网络图，借助Cytoscape 3.7.1对PPI进行可视化并筛选核心靶点。再使用R平台进行潜在靶点功能富集分析。结果：通过筛选得到Paeonolide抗AD潜在靶点52个，核心靶点为HSP90AA1、NFKB1、STAT1、MAPK1、PIK3R1、CDC42等，信号通路涉及Chemokine信号通路、AGE-RAGE信号通路、Toll样受体信号通路等。结论：丹皮酚原苷改善AD其机制可能依赖多靶点、多通路的特性发挥对AD的改善及治疗功效。

Abstract: Objective: To explore the mechanism of paeonolide in ameliorating Alzheimer’s disease (AD) based on network pharmacology. Methods: Targets of paeonolide were screened using the TargetNET, SwissTargetPrediction and SuperPRED databases. AD-related targets were retrieved by integrating the GeneCards, OMIM and TTD databases. The overlapping potential targets of paeonolide against AD were obtained via the Venny platform. A protein-protein interaction (PPI) network was constructed using the STRING database, visualized with Cytoscape 3.7.1, and core targets were screened. Functional enrichment analysis of the potential targets was performed using the R platform. Results: A total of 52 potential targets of paeonolide against AD were identified, with core targets including HSP90AA1, NFKB1, STAT1, MAPK1, PIK3R1 and CDC42. The main signaling pathways involved the chemokine signaling pathway, AGE-RAGE signaling pathway, and Toll-like receptor signaling pathway. Conclusion: Paeonolide may ameliorate and treat AD through a multi-target and multi-pathway regulatory mechanism.