基于网络药理学和实验验证研究补血益母丸治疗产后腹痛的作用机制

doi:10.5246/jcps.2023.09.057

中国药学(英文版) ›› 2023, Vol. 32 ›› Issue (9): 691-703.DOI: 10.5246/jcps.2023.09.057

• 【研究论文】 • 下一篇

基于网络药理学和实验验证研究补血益母丸治疗产后腹痛的作用机制

吴梦瑶¹, 刘璐², 张鹏¹^,^*(), 张乐乐³, 龚云¹, 杨秀伟²^,^*()

1. 株洲千金药业股份有限公司; 湖南株洲 412000
2. 北京大学医学部药学院天然药物及仿生药物全国重点实验室; 天然药物学系, 北京 100191
3. 成都大学基础医学院, 四川成都 610100

收稿日期:2023-02-16 修回日期:2023-04-23 接受日期:2023-07-15 出版日期:2023-09-30 发布日期:2023-09-30
通讯作者: 张鹏, 杨秀伟
作者简介:
+ E-mail: pengzhangbjmu@163.com
+ Tel.: +86-10-82801569, E-mail: xwyang@bjmu.edu.cn

Exploring the mechanism of Buxue Yimu Pills on postpartum abdominal pain through network pharmacology and experimental validation

Mengyao Wu¹, Lu Liu², Peng Zhang¹^,^*(), Lele Zhang³, Yun Gong¹, Xiuwei Yang²^,^*()

1 Zhuzhou Qianjin Pharmaceutical Co., Ltd. Zhuzhou 412000, Hunan, China
2 State Key Laboratory of Natural and Biomimetic Drugs, Department of Natural Medicines, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China
3 School of Basic Medical Sciences, Chengdu University, Chengdu 610100, Sichuan, China

Received:2023-02-16 Revised:2023-04-23 Accepted:2023-07-15 Online:2023-09-30 Published:2023-09-30
Contact: Peng Zhang, Xiuwei Yang

摘要/Abstract

摘要：

本研究通过网络药理学和实验验证, 探讨补血益母丸治疗产后腹痛的分子机制。通过TCMSP、SymMap、BATMAN-TCM和《中华人民共和国药典》筛选出补血益母丸的主要活性成分; 采用GeneGards数据库获得产后腹痛相关疾病靶点; 采用Cytoscape3.9.1软件和String数据库构建蛋白相互作用网络; 通过DAVID6.8数据库对GO和KEGG信号通路进行分析; 对分析结果构建“化合物-靶点”网络, 采用动物实验验证网络核心靶点, 采用免疫组化检测不完全流产模型大鼠相关蛋白的表达水平。网络学分析结果表明, 补血益母丸中的40种潜在活性成分可能影响ESR1、PGR、MMP2等40个相关靶点, 并调节HIF-1、TNF、雌激素等信号通路。免疫组化结果显示, 模型大鼠ERα、PR、MMP2蛋白表达水平均显著升高(P < 0.01)。给予补血益母丸后, PR表达水平升高(P < 0.01), ERα和MMP2表达水平显著降低(P < 0.05或P < 0.01)。补血益母丸可通过多成分、多靶点、多途径治疗产后腹痛, 可通过调节雌孕激素受体, 改善胶原代谢, 从而促进产后子宫恢复。

关键词: 补血益母丸, 中药, 产后腹痛, 网络药理学, 靶点

Abstract:

To investigate the molecular mechanisms of Buxue Yimu Pills (BYP) on postpartum abdominal pain (PAP) through network pharmacology and experimental validation, we filtered the main active components of BYP using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis (TCMSP), Symptom Mapping (SymMap), Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine (BATMAN-TCM) database, and Pharmacopoeia of the People’s Republic of China (ChP). The targets related to PAP were obtained from Genecards, and an intersection of genes was discovered. Subsequently, protein-protein interaction (PPI) networks were constructed using Cytoscape 3.9.0 and the String database. In addition, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to analyze the intersection of targets using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) 6.8. We constructed a compound-target (C-T) network based on the above analysis. Animal experiments were performed to verify the core targets, and immunohistochemistry was used to detect protein expression in incomplete abortion rats. Network pharmacology analysis suggested that 40 potentially active ingredients in BYP might affect 40 potential disease-related targets, such as ESR1, PGR, and MMP2, and regulate pathways, such as the HIF-1 signaling pathway, TNF signaling pathway, and Estrogen signaling pathway. According to immunohistochemistry, the protein expression levels of ERα, PR, and MMP2 in the model rats were significantly increased (P < 0.01). After administration of BYP, the expression level of PR was increased (P < 0.01), and the expression levels of ERα and MMP2 were decreased significantly (P < 0.05 or P < 0.01). BYP could treat PAP through a multi-component, multi-target, and multi-pathway approach, regulating estrogen and progesterone receptors and improving collagen metabolism, thereby promoting postpartum uterine recovery.

Key words: Buxue Yimu Pills, Traditional Chinese medicine, Postpartum abdominal pain, Network pharmacology, Target

Supporting:

吴梦瑶, 刘璐, 张鹏, 张乐乐, 龚云, 杨秀伟. 基于网络药理学和实验验证研究补血益母丸治疗产后腹痛的作用机制[J]. 中国药学(英文版), 2023, 32(9): 691-703.

Mengyao Wu, Lu Liu, Peng Zhang, Lele Zhang, Yun Gong, Xiuwei Yang. Exploring the mechanism of Buxue Yimu Pills on postpartum abdominal pain through network pharmacology and experimental validation[J]. Journal of Chinese Pharmaceutical Sciences, 2023, 32(9): 691-703.

图/表 7

Table 1. Basic information of 69 active ingredients in BYP.

Figure 1. PPI network.

Figure 2. Results of GO enrichment analysis.

Figure 3. A bubble chart for enrichment analysis of KEGG pathways. Note: The abscissa indicates the proportion of genes enriched in this pathway. The bubble size indicates the number of genes enriched in this pathway. The larger the bubble, the more genes are enriched, and the yellow color indicates the smaller the P value.

Figure 4. C-T network. Note: the blue nodes represent compounds; the green nodes represent the targets.

Figure 5. Effect of BYP on uterine morphology of model rats.

Figure 6. Effects of BYP on the expressions of ERα, PR, and MMP2 in medical-induced incomplete abortion rats. Immunohistochemistry images of ERα, PR, and MMP2 of the uterus tissues were captured, and average optical density was quantified. ##P < 0.01 vs. control group; *P < 0.05, ** P < 0.01 vs. model group.

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基于网络药理学和实验验证研究补血益母丸治疗产后腹痛的作用机制

Exploring the mechanism of Buxue Yimu Pills on postpartum abdominal pain through network pharmacology and experimental validation

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