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中华临床医师杂志(电子版) ›› 2023, Vol. 17 ›› Issue (12) : 1270 -1276. doi: 10.3877/cma.j.issn.1674-0785.2023.12.010

临床药学

红花平疣颗粒治疗扁平疣的网络药理学分析及羟基红花黄色素A的含量测定
俞俊霞, 台宗光, 程婷婷, 朱全刚†()   
  1. 233030　蚌埠，蚌埠医学院药学院;200443　上海，上海市皮肤病医院药剂科
    200443　上海，上海市皮肤病医院药剂科
  • 收稿日期:2023-08-10 出版日期:2023-12-15
  • 通信作者: 朱全刚

Network pharmacological analysis of Honghuapingyou granules for treatment of verruca plana and detection of hydroxysafflor yellow A

Junxia Yu, Zongguang Tai, Tingting Cheng, Quangang Zhu†()   

  1. School of Pharmacy, Bengbu Medical College, Bengbu 233030, China;Department of Pharmacy, Shanghai Skin Disease Hospital, Shanghai 200443, China
    Department of Pharmacy, Shanghai Skin Disease Hospital, Shanghai 200443, China
  • Received:2023-08-10 Published:2023-12-15
  • Corresponding author: Quangang Zhu
  • Supported by:
    Shanghai 2022 "Science and Technology Innovation Action Plan" Biomedical Science and Technology Support Project(22S21902700); National Natural Science Foundation of China(82172706)
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俞俊霞, 台宗光, 程婷婷, 朱全刚. 红花平疣颗粒治疗扁平疣的网络药理学分析及羟基红花黄色素A的含量测定[J]. 中华临床医师杂志(电子版), 2023, 17(12): 1270-1276.

Junxia Yu, Zongguang Tai, Tingting Cheng, Quangang Zhu. Network pharmacological analysis of Honghuapingyou granules for treatment of verruca plana and detection of hydroxysafflor yellow A[J]. Chinese Journal of Clinicians(Electronic Edition), 2023, 17(12): 1270-1276.

目的

以网络药理学系统分析红花平疣颗粒治疗扁平疣的主要活性成分、潜在治疗靶点及作用机制，并以此为基础建立红花平疣颗粒的质量控制指标。

方法

借助中药系统药理数据库和分析平台(TCMSP)数据库、SwissTargetPrediction数据库、中医药证候关联数据库(SymMap数据库)，筛选出红花平疣颗粒的主要活性成分及其作用靶点；借助人类基因综合数据库(Genecards数据库)、人类孟德尔遗传数据库(OMIM数据库)检索出扁平疣的相关靶点；借助蛋白质-蛋白质相互作用数据库(STRING数据库)构建潜在靶点的蛋白质互作网络(PPI)图，并利用Cytoscape 3.7.2软件构建“红花平疣颗粒-活性成分-作用靶点”网络图；借助基因功能注释分析数据库Matascape进行基因本体(GO)和京都基因与基因组百科全书(KEGG)富集分析，并利用Cytoscape软件构建“活性成分-核心靶点-信号通路”网络图；最后采用高效液相色谱(HPLC)法对红花平疣颗粒中主要指标成分羟基红花黄色素A进行含量测定。

结果

通过网络药理学筛选出157个活性成分，94个核心靶点。此外，红花平疣颗粒可能通过调控白细胞介素-17(IL-17)和缺氧诱导因子1(HIF-1)等信号通路发挥治疗扁平疣的作用。HPLC结果显示，羟基红花黄色素A在6~120 mg/L范围内线性关系良好(r=0.9996)，精密度、重复性、稳定性试验的相对标准偏差(RSD)值均<3%，平均回收率为96.17%~101.85%，RSD为2.19%(n=6)，其平均含量为0.0576 mg/g。

结论

通过网络药理学初步探讨红花平疣颗粒治疗扁平疣的作用机制，并对筛选出来的质控指标成分羟基红花黄色素A进行了定量研究，该研究为红花平疣颗粒治疗扁平疣的药效学及质量标准提升研究提供一定的依据。

关键词: 扁平疣, 红花平疣颗粒, 网络药理学, 羟基红花黄色素A, 质量标准
Objective

To systematically analyze the main active ingredients, potential therapeutic targets, and mechanism of action of Honghuapingyou granules in the treatment of verruca plana by network pharmacology, and to establish the quality control index for Honghuapingyou granules on this basis.

Methods

With the help of the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) database, the SwissTargetPrediction database, and the Symptom Mapping (SymMap) database, the main active components and targets of Honghuapingyou granules were screened. The relevant targets of verruca plana were retrieved with the help of the Human Gene Database GeneCards and the Online Mendelian Inheritance in Man (OMIM) database. The Protein-Protein Interaction Networks (PPI) diagram of potential targets was constructed with the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database, and the network diagram of "Honghuapingyou granules-active ingredient-target action" was constructed using Cytoscape 3.7.2 software. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed with the help of the gene function annotation analysis database Matascape, and the network diagram of the "active ingredient-core target-signaling pathway" was constructed with Cytoscape software. Finally, high-performance liquid chromatography (HPLC) was used to determine the content of hydroxysafflower yellow A, the main index component in Honghuapingyou granules.

Results

A total of 157 active ingredients and 94 core targets were screened through network pharmacology. In addition, Honghuapingyou granules play a role in the treatment of verruca plana possibly by regulating signaling pathways such as interleukin-17 (IL-17) and hypoxia-inducible factor 1 (HIF-1). The results of HPLC showed that the linear relationship between hydroxysafflower yellow A was good in the range of 6-120 mg/L (r=0.9996), the relative standard deviation (RSD) values of precision, repeatability, and stability were less than 3%, the average recovery rate was 96.17%-101.85%, the RSD was 2.19% (n=6), and the average content was 0.0576 mg/g.

Conclusion

The mechanism of action of Honghuapingyou granules in the treatment of verruca plana has been preliminarily explored through network pharmacology, and the quantitative study of hydroxysafflower yellow A, the selected quality control index component, provides a basis for the study of pharmacodynamics and quality standard improvement of Honghuapingyou granules in the treatment of verruca plana.

Key words: Verruca plana, Honghuapingyou granules, Network pharmacology, Hydroxysafflor yellow A, Quality standard
表1 本研究获取资料数据库的网址及作用
数据库 网址 作用
中药系统药理数据库和分析平台(TCMSP) https://old.tcmsp-e.com/tcmsp.php 获取中药活性成分及靶点
中医药证候关联数据库(SymMap) http://www.symmap.org/ 获取中药的活性成分
小分子药物靶点预测在线平(SwissTargetPrediction) http://swisstargetprediction.ch/ 获取化合物的靶点
蛋白质分析数据库(Uniprot) https://www.uniprot.org/ 规范靶点名称
人类基因综合数据库(GeneCards) https://www.genecards.org/ 获取疾病靶点基因
人类孟德尔遗传数据库(OMIM) https://www.omim.org/ 获取疾病靶点基因
韦恩图(Venny 2.1) https://bioinfogp.cnb.csic.es/tools/venny/ 获取疾病靶点和药物靶点的交集
蛋白质-蛋白质相互作用数据库(STRING) https://cn.string-db.org/ 查看蛋白之间相互作用关系
基因功能注释分析数据库(Metascape) https://metascape.org/gp/index.html 进行GO和KEGG分析
微生信 http://www.bioinformatics.com.cn/ 将富集的结果转换成正式的图
表2 红花平疣颗粒组方中药的共有成分
序号 Mol ID号 共有成分 中药
1 MOL000006 木犀草素(Luteolin) 红花、香附、僵蚕
2 MOL000098 槲皮素(Quercetin) 红花、香附、僵蚕
3 MOL000296 常春藤皂苷元(Hederagenin) 黄芪、三棱、莪术
4 MOL000354 异鼠李素(Iorhamnetin) 黄芪、香附
5 MOL000358 β-谷甾醇(Beta-sitosterol) 板蓝根、百部、赤芍、红花、三棱、香附
6 MOL000359 谷甾醇(Sitosterol) 百部、板蓝根、赤芍、川芎、熟地黄、香附
7 MOL000392 刺芒柄花素(Formononetin) 百部、黄芪、三棱
8 MOL000422 山柰酚(Kaempferol) 红花、黄芪、香附、僵蚕
9 MOL000449 豆甾醇(Stigmasterol) 百部、板蓝根、赤芍、熟地黄、红花、三棱、香附
10 MOL000953 胆固醇(CLR) 板蓝根、红花
11 MOL001771 γ-谷甾醇(Poriferast-5-en-3beta-ol) 板蓝根、红花
12 MOL002714 黄芩素(Baicalein) 赤芍、红花
13 MOL002776 黄芩苷(Baicalin) 赤芍、红花
表3 红花平疣颗粒部分中药活性成分作用靶点表
成分 靶点 中药
黄芩素(baicalein) PTGS2、BCL2、AR、RELA、TP53、AKT1、VEGFA、MMP9、HIF1A、MPO、IGF2、CYCS、APOD 红花、赤芍
山奈酚(kaempferol) PTGS2、PGR、BCL2、AR、RELA、TNF、AKT1、MMP1、HMOX1、STAT1、CYP1A1、ICAM1、CYP1B1 红花、黄芪、香附、僵蚕
木犀草素(luteolin) PTGS2、CCND1、IL10、BCL2L1、AR、IL4、RELA、CDKN1A、TP53、TNF、AKT1、VEGFA、MMP9、IL6、MMP2、NFKBIA、IL2、MMP1、HMOX1、ICAM1、EGFR、BCL2L1、MAPK1、RB1、CDK4、APP、PCNA、ERBB2、IFNG、XIAP、CD40LG 红花、香附
槲皮素(quercetin) PTGS2、CCND1、IL10、ADRB2、BCL2、BCL2L1、CASP8、AR、AKR1B1、PLAU、RELA、CDKN1A、TP53、TNF、AKT1、VEGFA、MMP9、HIF1A、MPO、IGF2、IL6、MMP2、NFKBIA、CXCL8、SOD1、IL2、MMP1、HMOX1、MYC、GJA1、STAT1、CYP1A1、ICAM1、CYP1B1、EGFR、BCL2L1、MAPK1、RB1、ERBB2、IFNG、CD40LG、MMP3、EGF、RAF1、IL1B、CCL2、DUOX2、HSPB1、PLAT、IL1A、COL3A1、CXCL11、CXCL10、CHUK、RASSF1、CTSD、IGFBP3、IRF1、RASA1 红花、香附、僵蚕
金合欢素(acacetin) PTGS2、FASN、ADRB2、BCL2、CASP8、AR、CDK2、RELA、CDKN1A、TP53、CYP19A1 板蓝根
刺芒柄花素(formononetin) PTGS2、ADRB2、ESR1、AR、ESR2、CDK2、IL4 百部、黄芪、三棱
β-胡萝卜素(beta-carotene) BCL2、CASP8、AKT1、VEGFA、MMP2、MMP1、HMOX1、ALB、CTNNB1、MYC、GJA1 红花
地黄苷d(rehmannioside d) CASP8、CYP19A1、CDK1、QARS、MMP13、MMP12、MMP8、IL2、STAT3 地黄
鞣花酸(ellagic acid) AR、CDK2、RELA、CDKN1A、VEGFA、MMP9、IGF2、MMP2、NFKBIA、CXCL8 赤芍
羟基红花黄色素a(hydroxysafflor yellow a) AKR1B1、CYP19A1、MMP13、MMP12、STAT3、IL1B、EDNRA、TERT、ATP2A1、ABCB1、MTOR、EP300、ACP1、IARS2 红花
表4 3批红花平疣颗粒的羟基红花黄色素A含量
批号 羟基红花黄色素A(mg/g)
2203001 0.0567
2302001 0.0588
2105001 0.0570
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