基于网络药理学和分子对接探讨陈皮治疗阿尔茨海默病的作用机制

Mechanism of Citri Reticulatae Pericarpium in treating Alzheimer’s disease based on network pharmacology and molecular docking

本研究通过网络药理学和分子对接阐明陈皮(Citri Reticulatae Pericarpium,CRP)治疗阿尔茨海默病(Alzheimer’s disease,AD)的作用机制。首先,在陈皮中筛选出98个有靶点的化合物和628个相关成分靶点,在疾病数据库中检索得到2483个AD靶点。随后,构建CRP-AD交叠靶点图和蛋白互作(PPI)网络图,对PPI网络图进行拓扑属性分析得到66个与CRP治疗AD密切相关的靶点,对66个靶点进行GO功能和KEGG通路富集分析,靶点在多条生物途径富集,包括松弛素信号通路、钙信号通路、HIF-1信号通路和IL-17信号通路。最后,对靶点和CRP活性成分进行分子对接验证,CRP的活性成分(黄烷酮、橘皮素、黄酮醇、香芹酚、紫苏醛)与靶点通过氢键连接,结合能小于0 kg/mol。本研究采用网络药理学和分子对接的方法系统的揭示了陈皮治疗阿尔茨海默病的作用机制,为以后科研以及临床研究提供理论依据。

The objective of this study was to elucidate the mechanism by which Citri Reticulatae Pericarpium(CRP)treated Alzheimer’s disease(AD)using network pharmacology and molecular docking.Initially,a screening process identified 98 target compounds and 628 related component targets within CRP.Additionally,2483 AD targets were retrieved from disease databases.Subsequently,an overlapping targets map was constructed,integrating CRP and AD targets,followed by the creation of a protein-protein interaction network map to identify 66 targets closely associated with the treatment of AD using CRP.These targets were identified through topological attribute analysis.To gain further insights,GO function and KEGG pathway enrichment analyses were conducted on the 66 identified targets.The results revealed enrichment in various biological pathways,including the relaxin signaling pathway,calcium signaling pathway,HIF-1 signaling pathway,and IL-17 signaling pathway.Finally,molecular docking verification was performed on the targets and active components of CRP.Active components,such as flavanone,tangeretin,flavonol,carvacrol,and perillaldehyde,were found to form hydrogen bonds with targets,with binding energies below 0 kg/mol.This study utilized network pharmacology and molecular docking methods to systematically elucidate the mechanism by which CRP treats AD.The findings provided a theoretical foundation for future research and clinical investigations.