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

Abstract

Objective The aim of this study is to investigate the underlying molecular mechanisms of Tiandan Qiyang Decoction (TDQYD) in treating erectile dysfunction (ED) and to provide insights for further research. Methods Integrated strategies including network pharmacology, molecular docking and molecular dynamics simulations were employed to explore the therapeutic 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, elenolide, 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-Methylechinatin-across multiple evaluation metrics. The ELISA results demonstrated that the serum EGFR levels in the control group, pretreatment 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 increase 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.

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