吉林大学学报(医学版) ›› 2023, Vol. 49 ›› Issue (5): 1296-1303.doi: 10.13481/j.1671-587X.20230524

• 临床研究 • 上一篇    

基于淫羊藿治疗下丘脑-垂体-肾上腺/性腺/甲状腺轴功能损伤药物有效化学成分及其作用靶点的网络药理学与分子对接技术分析

王春玲,吴思诺,于晓艳(),张伟东()   

  1. 吉林大学药学院药学系,吉林 长春 130021
  • 收稿日期:2022-12-30 出版日期:2023-09-28 发布日期:2023-10-26
  • 通讯作者: 于晓艳,张伟东 E-mail:yuxy@jlu.edu.cn;weidongzhang@jlu.edu.cn
  • 作者简介:王春玲(1999-),女,内蒙古自治区通辽市人,在读硕士研究生,主要从事肾脏疾病中药药理学方面的研究。
  • 基金资助:
    吉林省科技厅重点研发项目(20220204081YY)

Analysis on network pharmacology and molecular docking technique based on effective chemical components and action targets of epimedium in treatment of hypothalamus-pituitary- adrenal gland/ gonad / thyroid gland axis function damage

Chunling WANG,Sinuo WU,Xiaoyan YU(),Weidong ZHANG()   

  1. Department of Pharmaceutical Sciences,School of Pharmacy,Jilin University,Changchun 130021,China
  • Received:2022-12-30 Online:2023-09-28 Published:2023-10-26
  • Contact: Xiaoyan YU,Weidong ZHANG E-mail:yuxy@jlu.edu.cn;weidongzhang@jlu.edu.cn

摘要:

目的 采用网络药理学方法联合分子对接技术分析淫羊藿治疗下丘脑-垂体-肾上腺/性腺/甲状腺轴功能损伤药物有效化学成分及其作用靶点,并初步阐明其作用机制。 方法 采用中药系统药理学(TCMSP)数据库和分析平台结合相关文献资料获取淫羊藿的有效化学成分及其对应的靶点蛋白,采用Uniprot数据库将靶点蛋白信息标准化得到对应的标准基因名,检索GeneCards 数据库和DisGeNET数据库收集下丘脑-垂体-肾上腺/性腺/甲状腺轴功能损伤的相关靶点基因,采用Cytoscape 3.7.1软件绘制淫羊藿有效化学成分和疾病作用靶点关系的网络图,采用STRING数据库绘制药物与疾病的交集靶点的蛋白-蛋白相互作用(PPI)网络图,采用基迪奥生物信息平台(OmicShare)进行基因本体(GO)功能富集分析和京都基因与基因组百科全书(KEGG)信号通路富集分析,采用Pymol软件和Autodock Tools软件进行淫羊藿药材有效化学成分与下丘脑-垂体-肾上腺/性腺/甲状腺轴功能损伤靶点蛋白的分子模拟对接和可视化。 结果 筛选得到27个淫羊藿有效化学成分和217个相对应作用靶点,下丘脑-垂体-肾上腺/性腺/甲状腺轴功能损伤靶点基因465个,其中62个靶点基因与淫羊藿治疗下丘脑-垂体-肾上腺/性腺/甲状腺轴功能损伤有密切关联。得到淫羊藿关键有效成分为槲皮素、木樨草素、山柰酚和淫羊藿苷等,关键靶点蛋白为含半胱氨酸的半胱氨酸蛋白酶3(Caspase-3)、白细胞介素6(IL-6)、低聚糖(FOS)、肿瘤坏死因子(TNF)、低氧诱导因子1α(HIF1A)、血管内皮生长因子A(VEGFA)、白细胞介素1B(IL-1β)、雌激素受体1(ESR1)、前列腺素内过氧化物合酶2(PTGS2)和基质金属蛋白酶9(MMP-9)等。KEGG信号通路富集分析,其共同靶点主要富集于免疫炎症、激素调节和能量代谢等相关通路上。分子对接,淫羊藿中的潜在有效成分与IL-6、PTGS2、醛糖还原酶(AR)和促分裂原活化蛋白激酶1(MAPK1)等靶点蛋白有较好的亲和作用。 结论 淫羊藿可通过多靶点和多通路在抗炎免疫、激素调节及能量代谢等方面对下丘脑-垂体-肾上腺/性腺/甲状腺轴功能损伤发挥潜在的治疗作用。

关键词: 淫羊藿, 下丘脑-垂体-肾上腺/性腺/甲状腺轴功能损伤, 网络药理学, 富集分析, 分子对接

Abstract:

Objective: To analyze the effective chemical components and their action targets of epimedium in the treatment of hypothalamus-pituitary-adrenal gland/gonad/thyroid gland axis functional damage by using network pharmacology and molecular docking technology, and to preliminarily clarify its mechanism. Methods The effective chemical components and their corresponding target proteins of epimedium were screened by Traditional Chinese Medicine Systems Pharmacology (TCMSP) Database and Analysis Platform combined with the relevant literatures, and the Uniprot Database was used to standardize the target protein informations to get the corresponding standard gene names; the relevant target genes of hypothalamus-pituitary-adrenal gland/gonad/thyroid gland axis function damage were collected from the GeneCards Database and DisGeNET Database;the network of the relationship between the effective chemical components of the epimedium and their action targets was constructed by Cytascape 3.7.1 Software; the protein-protein interaction (PPI) network diagram of drug-disease of effective chemical components and target proteins of hypothalamus-pituitary-adrenal gland/gonad/thyroid gland axis function damage was constructed by STRING Database. Gene Ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genome (KEGG) signaling pathway enrichment analysis were performed by OmicShare Database;molecular simulation docking and visualization were done by Pymol Software and the Autodock Tools Software. Results A total of 27 effective chemical components and 217 corresponding action targets of epimedium, and 465 target genes of hypothalamus-pituitary-adrenal gland/gonad/thyroid gland axis function damage were screened out, of which 62 target genes were closely related to the treatment of hypothalamus-pituitary-adrenal gland/gonad/thyroid gland axis function damage by epimedium.Quercetin,luteolin,kaempferol, and icariin and so on were the key effective chemical components, and the key target proteins were Cysteine protease 3 containing cysteine(Caspase-3), interleukin-6(IL-6), oligosaccharides (FOS), tumor necrosis factor(TNF), hypoxia inducible factor-1 alpha (HIF1A), vascular endothelial growth factor A(VEGFA), interleukin-1β(IL-1β), estrogen receptor 1 (ESR1),recombinant prostaglandin endoperoxide synthase 2(PTGS2), matric metallopeptidase 9(MMP-9),and so on.The KEGG signaling pathway enrichment analysis results showed that the common targets were mainly concentrated in the pathways related to immune inflammation, hormone regulation, and energy metabolism. The molecular docking results showed that the potential active components of epimedium had a good affinity with IL-6, PTGS2, aldose reductase(AR), and mitogen-activated protein kinase 1(MAPK1)targets. Conclusion Epimedium may play a potential therapeutic role in the treatment of hypothalamus-pituitary-adrenal gland/gonad/thyroid gland axis function damage in the aspects of anti-inflammatory immunity, hormone regulation, and energy metabolism through multiple targets and pathways.

Key words: Epimedium, Hypothalamus-pituitary-adrenal gland/gonad/thyroid gland axis function damage, Network pharmacology, Enrichment analysis, Molecular docking

中图分类号: 

  • R966