天然产物研究与开发 ›› 2025, Vol. 37 ›› Issue (7): 1356-1366.doi: 10.16333/j.1001-6880.2025.7.017 cstr: 32307.14.1001-6880.2025.7.017

• 数据研究 • 上一篇    下一篇

基于网络药理学和动物实验探究丹参-黄芪药对治疗多囊卵巢综合征的作用机制

母伟林1,邵欣欣2,5,刘青芝3,张 匣1,宋田禹1,高鹏飞1,陈 聪4,5*,胡亚洁1*   

  1. 1山东中医药大学中医学院;2山东中医药大学第一临床医学院;3山东中医药大学药学院;4山东中医药大学中医文献与文化研究院;5山东中医药大学中医药经典理论教育部重点实验室,济南250355
  • 出版日期:2025-07-28 发布日期:2025-07-28
  • 基金资助:
    国家科技部重点研发计划(2017YFC1702700);山东省高等学校中医药数字人文青年创新团队项目(2023RW093);济南市科技型中小企业创新能力提升工程项目

Mechanism of Salviae Miltiorrhizae Radix et Rhizoma-Astragali Radix drug pair in the treatment of polycystic ovary syndrome based on network pharmacology and animal experiments

MU Wei-lin1,SHAO Xin-xin2,5,LIU Qing-zhi3,ZHANG Xia1,SONG Tian-yu1,GAO Peng-fei1,CHEN Cong4,5*,HU Ya-jie1*   

  1. 1College of Traditional Chinese Medicine,Shandong University of Traditional Chinese Medicine;2The First Clinical College,Shandong University of Traditional Chinese Medicine;3College of Pharmacy,Shandong University of Traditional Chinese Medicine;4Institute of Chinese Medical Literature and Culture,Shandong University of Traditional Chinese Medicine;5 Key Laboratory of Traditional Chinese Medicine Classic Theory(Shandong University of Traditional Chinese Medicine),Ministry of Education,Jinan 250355,China
  • Online:2025-07-28 Published:2025-07-28

摘要:

基于网络药理学及动物实验探究中药药对丹参-黄芪(Salviae Miltiorrhizae Radix et Rhizoma-Astragali Radix,SMR-AR)治疗多囊卵巢综合征(polycystic ovary syndrome,PCOS)的改善作用及其机制。首先通过TCMSP、HERB、PubChem、GeneCards等数据库获取SMR-AR的活性成分,预测该药对的作用靶点,筛选PCOS疾病靶点,然后利用微生信平台、STRING数据库、Cytoscape 3.9.1软件进行拓扑分析查看SMR-AR治疗PCOS的潜在靶点,使用DAVID数据库对潜在靶点进行GO和KEGG富集分析。最后,通过建立PCOS大鼠模型进行实验验证。SMR-AR共检索到109个活性成分,共预测作用靶点850个,通过与2 169个PCOS疾病靶点进行交集映射,获得SMR-AR治疗PCOS的潜在靶点287个,主要涉及癌症、脂酰肌醇-3-激酶/蛋白激酶B(phosphatidylin-ositol-3-kinase/protein kinase B,PI3K/AKT)通路、癌症中的蛋白聚糖、脂质与动脉粥样硬化、癌症中的MicroRNAs、化学致癌受体激活通路、卡波西肉瘤相关疱疹病毒感染、焦点粘附等信号通路。动物实验结果显示,SMR-AR可显著下调PCOS大鼠血清中睾酮、黄体生成素、空腹血糖及空腹胰岛素水平,使胰岛素抵抗稳态模型评估的数值明显降低,显著上调卵泡刺激素水平,卵巢组织病理变化得到明显改善,促进卵巢组织PI3K/AKT信号通路中PI3K、p-AKT/AKT、细胞周期蛋白依赖性激酶4的蛋白表达。综上,本研究初步揭示SMR-AR通过多成分多靶点途径治疗PCOS可能与PI3K-AKT信号通路有关,从而促进PCOS大鼠卵泡发育和成熟,改善性激素失衡及调节糖代谢。

关键词: 丹参-黄芪, 多囊卵巢综合征, 网络药理学, 实验验证, 作用机制

Abstract:

This study aims to investigate the ameliorative effects and mechanisms of Salviae Miltiorrhizae Radix et Rhizoma-Astragali Radix (SMR-AR) in the treatment of polycystic ovary syndrome (PCOS) based on network pharmacology and animal experiments.Firstly,we obtained the active ingredients of SMR-AR through TCMSP,HERB,PubChem,GeneCards and other databases,predicted the target of action of the herb pair,and screened the disease targets of PCOS,and then we used the weishengxin platform,the STRING database,and the Cytoscape 3.9.1 software to perform the topological analyses to view the potential effects of SMR-AR in the treatment of PCOS,and GO and KEGG enrichment analyses of potential targets were performed using the DAVID database.Finally,experimental validation was carried out by establishing a rat model of PCOS.A total of 109 active ingredients were retrieved by SMR-AR,with a total of 850 predicted targets of action,through intersection mapping with 2 169 PCOS disease targets,287 potential targets of SMR-AR for the treatment of PCOS were obtained,which mainly involving cancer,phosphatidylin-ositol-3-kinase/protein kinase B (PI3K/AKT) pathway,proteoglycans in cancer,lipids and atherosclerosis,microRNAs in cancer,chemical carcinogenesis-receptor activation,kaposi sarcoma-associated herpesvirus infection,focal adhesion and other signaling pathways.The results of animal experiments showed that SMR-AR significantly down-regulated of testosterone,luteinising hormone,fasting blood glucose and fasting insulin levels in serum of PCOS rats,resulting in significantly lower values assessed by the homeostatic model of insulin resistance,significantly up-regulated follicle stimulating hormone levels in serum of PCOS rats.The histopathological changes of ovarian tissue were significantly improved,and the protein expression levels of PI3K,p-AKT/AKT,and cyclin dependent kinase 4 in the PI3K/AKT signaling pathway was promoted in ovarian tissue.In summary,this study preliminarily reveals that SMR-AR could be related to the PI3K-AKT signaling pathway through a multi-component and multi-targeted pathway for the treatment of PCOS,which could promote follicular development and maturation,improve sex hormone imbalance and regulate glucose metabolism in PCOS rats.

Key words: Salviae Miltiorrhizae Radix et Rhizoma-Astragali Radix, polycystic ovary syndrome, network pharmacology, experimental verification, mechanism of action

中图分类号:  R285