Objective To investigate the mechanism of testicular injury induced by tripterygium glycosides by network pharmacology,explore the potential targets and mechanism of action,and conduct animal experiments to verify it,so as to provide a new research strategy for the rational use of the drug.Methods Based on literature search and TCMSP,GeneCards,OMIM,and Metascape databases,the information of active ingredients in tripterygium glycosides was mined,and the main active ingredients and targets associated with testicular injury were selected to construct the protein interaction(PPI)network.Metascape database was used to conduct gene ontology(GO)gene annotation and Kyoto Encyclopedia of Genes and Genes(KEGG)pathway enrichment analysis for core targets,and molecular docking and animal experiments were conducted.Results A total of 18 active components of tripterygium glycosides were screened,among which the main active components were triptonoterpenol,celabenzine,triptoquinone A.Estrogen receptor 1(ESR1)and epidermal growth factor receptor(EGFR)were the core targets.KEGG enrichment analysis of the active components of tripterygium glycosides on testicular injury mainly involved cancer signaling pathway,cAMP signaling pathway,Ras signaling pathway,etc.The results of network pharmacology and molecular coupling analysis showed that celafurine was well bound to protein kinase B1(Akt1),triptoquinone A was well bound to tumor necrosis factor(TNF),and celabenzine was well bound to ESR1.The mRNA expression levels of ESR1 and EGFR in tripterygium glycosides group were significantly increased(P<0.05).Conclusion Mechanism of testicular injury induced by tripterygium glycosides may be closely related to the core targets such as ESR1 and EGFR.
tripterygium glycosidestesticular injurynetwork pharmacologytriptonoterpenolcelabenzinetriptoquinone A