摘要

【摘要】
目的：基于网络药理学及分子对接探讨柴胡疏肝散治疗高泌乳素血症的作用机制及临床初步探索。

方法：使用TCMSP平台与UniProt数据库筛选药物的主要活性成分及其作用靶点；检索GeneCards和Disgent数据库，OMIM数据库作为补充，获得高泌乳素血症（hyperprolactinemia、HPRL）的疾病相关靶点；利用Venny 2.1在线绘制韦恩图；使用String在线网站分析蛋白质-蛋白质相互作用(PPI)，构建其网络；应用Cytoscape软件构建药物活性成分-HPRL靶点网络；对潜在靶点通过Meatscape数据库行GO基因本体功能及KEGG通路富集分析，应用微生信在线平台进行可视化分析。利用AutoDock vina软件1.2.3对活性成分与核心靶点进行分子对接，PyMOL软件3.10进行可视化分析。通过临床，试验柴胡疏肝散对HPRL的改善效果。

结果：得到139种活性成分，与治疗疾病相关的有槲皮素、木犀草素及芒柄花黄素等；得到柴胡疏肝散与HPRL相关靶点58个，其中核心靶点有雌激素受体1、转录激活因子3、肿瘤坏死样子等；通过GO富集分析获取GO条目共44个，包括腺体发育、对激素的反应、MAPK级联调控等；通过KEGG富集分析获取信号通路共15条，包括癌症、多巴胺能突触通路等；分子对接及可视化显示活性成分及核心靶点具有良好的对接效能。临床试验表明，中药干预3周后患者的垂体泌乳素显著下降。

结论：本研究初步探讨了柴胡疏肝散治疗HPRL的成分、靶点、作用机制。

关键词：柴胡疏肝散；高泌乳素血症；作用机制；临床探索

ABSTRACT

[Abstract]
Objective: To investigate the mechanism of Chaihu Shugan Powder in the treatment of hyperprolactinemia based on network pharmacology and molecular docking and its preliminary clinical exploration.

Methods: The TCMSP platform and UniProt database were used to screen the main active ingredients and their targets of drugs; GeneCards, Disgent and OMIM databases were searched to obtain disease related targets of hyperprolactinemia（HPRL）; Venn diagrams were drawn online using Venny 2.1; protein-protein interaction (PPI) were analyzed using the String online website to construct their networks; Cytoscape software was applied to construct the drug active component-HPRL target network; GO gene ontology function and KEGG pathway enrichment analysis were performed for potential targets through the Meatscape database, and visualization analysis was performed using the Microbiology Information Online Platform. Molecular docking of the active ingredient to the core target was performed using AutoDock vina software 1.2.3 and visualized by PyMOL software 3.10. Finally, Chaihu Shugan Powder was clinically tested to improve hyperprolactinemia. Result: A total of 139 active components such as quercetin, luteolin and formonetin associated with the treatment of diseases were obtained.;Fifty-eight targets related to HPRL were obtained for Chaihu Shugan Powder, and the core targets were estrogen receptor 1, transcriptional activator 3 and tumor necrosis appearance ,etc.;A total of 44 GO entries were obtained by GO enrichment analysis, including gland development, response to hormones, and MAPK cascade regulation, etc.;A total of 15 signaling pathways were obtained by KEGG enrichment analysis, including cancer and dopaminergic synaptic,etc; Molecular docking and visualization showed that the active components and core targets had good docking efficacy. Clinical trials have shown a significant decrease in pituitary prolactin in patients after 3 weeks of TCM intervention.

Conclusion  : This study preliminarily investigated the components, targets,and mechanisms of Chaihu Shugan Powder in the treatment of HPRL.

Key words: Chaihu Shugan Powder ; HPRL ; Mechanisms ，Clinical exploration