目的 通过哌甲酯靶点导向的中药网络药理学方法，探讨中药治疗注意缺陷多动障碍（ADHD）的分子机制和用药规律。方法 采用网络药理学方法，通过SwissTargetPrediction和多个数据库预测哌甲酯与ADHD的共同靶基因，基于ADME参数和Lipinski规则筛选作用于共同靶基因的化合物。利用GeneMANIA和Cytoscape构建蛋白质-蛋白质相互作用（PPI）网络，Biozeron Cloud Platform进行基因本体（GO）和京都基因与基因组百科全书（KEGG）分析，揭示靶基因功能。构建“靶基因-化合物-中药”网络，筛选候选中药，分析候选中药属性和功能，并采用微词云平台进行数据可视化。结果 共识别出49个哌甲酯与ADHD的共同靶基因。共同靶基因PPI网络和GO/KEGG分析揭示了神经系统和神经递质信号传递的关键通路。筛选出567个化合物和416个候选中药。构建的网络图识别出甘草、丹参等与ADHD治疗相关的高频中药，通过对候选中药的性、味、归经和功能的频次分析，发现候选药物性味以苦、寒为主，归经以肝、肺、胃较为突出，清热、解毒、止痛、消肿等功能频繁出现。结论 以哌甲酯治疗ADHD的靶点为导向，运用中药网络药理学的方法，逆向解析了治疗ADHD的分子机制和用药规律。候选药物显示出多成分、多靶点、多路径治疗ADHD的潜力，为ADHD的临床和基础研究的深入探索提供了新的思路。

Objective To explore the molecular mechanisms and medication patterns of traditional Chinese medicine (TCM) in the treatment of attention deficit hyperactivity disorder (ADHD) using a network pharmacology approach guided by methylphenidate targets. Methods A network pharmacology method was employed to predict common targets of methylphenidate and ADHD using Swiss TargetPrediction and multiple databases. Compounds acting on these common targets were screened based on ADME parameters and Lipinski's rules. PPI networks were constructed using GeneMANIA and Cytoscape, and GO and KEGG analyses were performed using Biozeron Cloud Platform to reveal the functions of the targets. A "target-compound-TCM" network was constructed to screen candidate TCMs, analyze their properties and functions, and the Microcloud platform was used for data visualization. Results A total of 49 common target genes between methylphenidate and ADHD were identified. Core target gene PPI networks and GO/KEGG analyses revealed key pathways in the nervous system and neurotransmitter signaling. A total of 567 compounds and 416 candidate TCMs were screened. The constructed network identified high-frequency TCMs related to ADHD treatment, such as licorice and salvia, and through frequency analysis of the properties, flavors, meridians, and functions of candidate TCMs, it was found that the candidate drugs were predominantly bitter and cold, with liver, lung, and stomach meridians being prominent, and functions such as heat-clearing, detoxification, analgesia, and anti-inflammatory effects were frequently observed. Conclusion This study, guided by the targets of methylphenidate in treating ADHD, used network pharmacology methods to reverse-engineer the molecular mechanisms and medication patterns of ADHD treatment. The candidate drugs showed potential for treating ADHD with multiple components, targets, and pathways, providing new insights for in-depth exploration of clinical and basic research on ADHD.

R285.5

国家自然科学基金青年项目（82104300）；武汉市卫生健康委中医类科研项目（WZ21A07， WZ22Q07）；武汉药学会第二届医院药学学科发展项目孵化营（WHPA202307007）