佛手散治疗血管性痴呆的系统药理学作用机制研究

Investigating the Mechanisms of Foshou San in the Treatment of Vascular Dementia using Systematic Pharmacology Approach

目的探索佛手散(当归、川考组成)治疗血管性痴呆(Vascular dementia,VaD)的药效物质基础及其作用机制。方法采用网络药理学策略与方法,首先构建佛手散化学成分数据库,经ADME筛选潜在的活性成分再应用计算机模型进行靶标预测,对预测的靶标进行基因本体论以及多层次数据整合网络分析,从而全面深入地揭示佛手散治疗VaD的作用机制。结果共收集了佛手散的296个化学成分,经过ADME筛选获得56个活性化合物。经靶标预测,得到222个蛋白靶标,基因本体论可知预测靶点主要在质膜、内质网等部位发挥氧化还原酶活性、催化活性等为代表的分子功能,从而参与能量代谢等生物过程。网络整合分析可知,佛手散主要作用于3个VaD相关的病理模块:突触可塑性调节模块、钙稳态调节模块以及G蛋白偶联受体模块。结论系统药理学方法可高效、全面地探索佛手散治疗血管性痴呆的作用机制。

Objective To investigate the bioactive ingredients and therapeutic mechanisms of Foshou san in the treatment of vascular dementia(VaD).Methods Based on the system pharmacology approach,we firstly collected the chemical compounds of Foshou san from the Chinese medicine database or by test mining method.Then the computer prediction model was used to predict the targets of potential bioactive compounds in Foshou san.Using gene ontology and multi-level data integration network analysis,the therapeutic mechanisms of action of Foshou san in the treatment of VaD were comprehensively revealed.Results A total of 296 chemical constituents of Foshou san were collected and 56 active compounds were obtained after ADME screening.Relying the target prediction model,a total of 222 protein targets were obtained.The gene ontology analysis indicates that the predicted target mainly work in the plasma membrane and endoplasmic reticulum with representative molecular functions,such as,oxidoreductase activity and catalytic activity,involve in the biological processes like energy metabolism.Network integration analysis demonstrated that Foshou san mainly regulates three VaD-associated pathological modules:synaptic plasticity regulation module,calcium homeostasis regulation module,and G protein coupled receptor module.Conclusion The system pharmacology approach can effectively and comprehensively explore the mechanisms of Foshou san for the treatment of vascular dementia.