中国药物警戒 ›› 2023, Vol. 20 ›› Issue (7): 783-790.
DOI: 10.19803/j.1672-8629.20220569

• 基础与临床研究 • 上一篇    下一篇

乳腺结重痛轻凝胶贴膏的成型性及治疗乳腺增生作用机制研究

苏月芬1, 郑婧柔1Δ, 宫贺1,2, 谢广通1,3, 张洁1, 赛春梅1*   

  1. 1济宁医学院药学院,山东 日照 276826；
    2广东药科大学中药学院,广东 广州 510006；
    3贵州中医药大学药学院,贵州 贵阳 550025
  • 收稿日期:2022-09-29 出版日期:2023-07-15 发布日期:2023-07-14
  • 通讯作者: *赛春梅,女,博士,副教授·硕导,中药物质基础研究与新药开发。E-mail: saichunmei1980@163.com
  • 作者简介:苏月芬,女,本科,中药学。△为并列第一作者。
  • 基金资助:
    济宁医学院大学生创新创业项目（CX2021061）; 国家自然科学基金资助项目（31800282）

Formability and mechanism of breast nodule pain-alleviating gel plaster for the treatment of breast hyperplasia

SU Yuefen1, ZHENG Jingrou1Δ, GONG He1,2, XIE Guangtong1,3, ZHANG Jie1, SAI Chunmei1,*   

  1. 1College of Pharmacy, Jining Medical University, Rizhao Shandong 276826, China;
    2School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou Guangdong 510006, China;
    3School of Pharmacy, Guizhou University of Chinese Medicine, Guiyang Guizhou 550025, China
  • Received:2022-09-29 Online:2023-07-15 Published:2023-07-14

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摘要： 目的 优化基质处方,制备乳腺结重痛轻凝胶贴膏剂,并通过网络药理学和分子对接技术探讨其治疗乳腺增生的潜在作用机制。方法 以初黏力、持黏力及综合感官为评价指标,采用正交设计对乳腺结重痛轻贴膏的基质处方进行优化,考察凝胶贴膏的成型性。借助网络药理学,通过TCMSP、Targetnet、Genecards、OMIM等数据库检索获取该制剂活性成分和乳腺增生的作用靶点,利用Venny工具筛选交集靶点,并运用Cytoscape软件构建药物-活性成分-靶点网络。运用String数据库对交集靶点进行蛋白-蛋白相互作用（PPI）分析,并使用Metascape数据库对交集靶点进行KEGG和GO通路富集分析。最后,借助AutoDockTools和PyMoL软件进行分子对接验证。结果 正交试验优选出乳腺结重痛轻凝胶贴膏基质处方为溶胀比1∶40的卡波姆20 mL,3 g·mL-1的药液20 mL,甘油7 mL,0.1 g·mL-1的对羟基苯甲酸甲酯1.5 mL。基于网络药理学,筛选出结重痛轻方的有效成分45个,以及活性成分与乳腺增生的交集靶点49个,包括ESR1、EGFR等,参与调节Pathways in cancer、Proteoglycans in cancer、Chemical carcinogenesis-receptor activation等信号通路发挥治疗乳腺增生的作用。经分子对接发现,主要活性成分木犀草素、山柰酚与核心靶点EGFR、AR结合能力较强。结论 按照最佳工艺制备的乳腺结重痛轻凝胶贴膏外观涂布均匀,具有良好的黏附性与赋形性,可为进一步的工艺开发提供参考。乳腺结重痛轻方可能通过调控EGFR、AR、STAT3等关键靶点,干预EGFR/PI3K/Akt、JAK/STAT等信号通路,从调节激素水平、细胞周期、抑制血管生成等方面发挥治疗乳腺增生的作用。

关键词: 乳腺结重痛轻凝胶贴膏, 乳腺增生, 基质处方, 正交设计, 网络药理学, 分子对接, 作用机制

Abstract: Objective To optimize the matrix formulation, prepare a breast nodule pain-alleviating gel plaster (BNPGP), and explore its potential mechanism for the treatment of breast hyperplasia via network pharmacology and molecular docking technology. Methods With the “initial adhesion, cohesive strength and comprehensive sensory organs” as evaluation indexes, the matrix prescription of BNPGP was optimized by orthogonal design, and its formability was investigated. All the targets of the active components and breast hyperplasia were retrieved from such databases as TCMSP, Targetnet, Genecards, OMIM with network pharmacology. The Venny tool was used to screen the intersection targets. The drug-active component-target network was established with Cytoscape software, and protein-protein interaction (PPI) analysis was performed on the intersection targets using String database. KEGG and GO pathway enrichment analysis was performed on the intersection targets using Metascape database. Finally, molecular docking verification was carried out with AutoDockTool and PyMoL software. Results Orthogonal test optimized the matrix prescription of BNPGP as follows: carbomer 20 mL at a swelling ratio of 1 : 40, 20 mL drug solution of 3 g·mL-1, 7 mL glycerol, and 1.5 mL methyl p-hydroxybenzoate of 0.1 g·mL-1. Based on network pharmacology, 45 effective components of BNPGP and 49 intersection targets between active components and breast hyperplasia were screened, including ESR1 and EGFR, which were involved in regulating Pathways in cancer, Proteoglycans in cancer, and Chemical carcinogenesis-receptor activation in the treatment of breast hyperplasia. Molecular docking showed that the main active components-luteolin and kaempferol-had strong binding ability to core targets EGFR and AR. Conclusion BNPGP prepared according to this optimal process has uniform appearance, good adhesion and formability, which can provide reference for the development of processes. BNPGP may play a role in the treatment of breast hyperplasia by regulating hormone levels and cell cycle, inhibiting angiogenesis by regulating key targets such as EGFR, AR, STAT3, and intervening in EGFR/PI3K/Akt, JAK/STAT signaling pathways.

Key words: breast nodule pain-alleviating gel plaster, breast hyperplasia, matrix prescription, orthogonal design, network pharmacology, molecular docking, mechanism

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