Therapeutic mechanism of Tiandan Qiyang Decoction in erectile dysfunction:An integrated approach combining network pharmacology,and molecular dynamics simulations

LU Yang; WANG Jian; WU Yancheng; YE Siyuan; PIAO Zhenrong; TENG Fengmeng; ZHANG Maosen

doi:10.13263/j.cnki.nja.2026.02.007

Abstract：Objective The aim of this study is to investigate the underlying molecular mechanisms of Tiandan Qiyang De-coction(TDQYD)in treating erectile dysfunction(ED)and to provide insights for further research.Methods Integrated strat-egies including network pharmacology,molecular docking and molecular dynamics simulations were employed to explore the ther-apeutic mechanisms of TDQYD for ED.Results A total of 140 active ingredients,1 143 associated target proteins,513 highly relevant ED-related disease targets,and 176 potential therapeutic targets were identified.The core targets such as AKT1,ESR1/2,IL-6,IL-1B,EGFR,VEGFA,and PTGS2 were identified by PPI analysis.KEGG pathway enrichment analysis revealed that the formulation primarily regulates key signaling pathways,including AGE-RAGE,Prolactin,EGFR,HIF-1,Prostate cancer,Endocrine resistance,Serotonergic synapse,Lipid and atherosclerosis,etc.Network and Sankey diagram analyses highlighted the seven most prominent active compounds:isoliquiritigenin 4-methylether,Isoliquiritigenin,3-deoxysappanchalcone,elenol-ide,micheliolide,bigelovin and 4-O-methylchinatin,while the most central core targets were EGFR,PTGS2,PIK3CA,GSK3B,and ESR1/2.Molecular docking simulations demonstrated strong binding affinities between the active components of TDQYD and the predicted therapeutic targets.Moreover,molecular dynamics simulations confirmed stable and robust interactions for the top-ranked complex pairs—ESR2_Bigelovin,ESR2_Micheliolide,EGFR_Isoliquiritigenin,and EGFR_4-O-Methylechina-tin—across multiple evaluation metrics.The ELISA results demonstrated that the serum EGFR levels in the control group,pre-treatment group,and posttreatment group were(244.12±57.16)pg/mL,(356.39±179.10)pg/mL and(263.01±122.08)pg/mL,respectively,showing a significant decrease after treatment(P＜0.05).The corresponding serum ER levels were(93.39±70.61)ng/L,(47.44±11.97)ng/L and(69.65±48.67)ng/L,respectively,indicating a significant in-crease following treatment(P＜0.01).Serum PTGS2 levels were measured as(3.55±1.58)ng/mL,(5.54±2.53)ng/mL and(3.84±1.61)ng/mL,respectively,and exhibited a significant reduction after treatment(P＜0.05).GSH-Px levels were(46.07±15.27)pmol/mL,(31.55±5.37)pmol/mL and(39.13±11.97)pmol/mL,respectively,and showed a significant elevation posttreatment(P＜0.01).Conclusion The core targets of TDQYD in the treatment of ED may be EGFR,PTGS2 and ER.This prescription acts on EGFR,HIF-1 and other pathways to improve ED by up-regulating ER,GSH-Px,and down-regulating EGFR,PTGS2 and other targets.