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