[Exploration of the multi-target mechanisms of Shenju Yin in treating sperm DNA damage: An integrated study combining network pharmacology, molecular docking, and dynamics simulation].

Abstract

Objective To explore the potential pharmacological targets and mechanisms of action of Shenju Yin, a formula derived from a renowned classic prescription, in treating sperm DNA damage (SDD) by integrating network pharmacology, molecular docking, and molecular dynamics simulation techniques. Methods Potential active ingredients of Shenju Yin were retrieved via the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and the Bioinformatics Analysis Tool for Molecular mechanism of Traditional Chinese Medicine (BATMAN-TCM 2.0). Relevant target genes for SDD were identified by cross-referencing the OMIM and GeneCards databases. The Cytoscape 3.10.0 software was employed to construct and visually analyze protein-protein interaction networks and a "disease-target-gene" network. Molecular docking validation of core active ingredients with target protein structures was performed using AutoDockTools-1.5.7. The top three complexes with the strongest binding affinity from docking were subjected to molecular dynamics simulation using Gromacs (2025.2). Results Nine core active components were screened including quercetin, palmitic acid, myristic acid, stearic acid, benzoic acid, myrtenol, kaempferol, luteolin and octanol. Nine core targets including TP53, AKT1, JUN, ESR1, TNF, SRC, IL6, BCL2 and CTNNB1were identified , along with three key pathways such as the Hallmark of Cancer Cell Proliferation Persistence, Gastrin Signaling Pathway and Cancer Pathway. Validation demonstrated strong binding for three complexes: BCL2-luteolin, TP53-kaempferol, and BCL2-quercetin. Conclusion Shenju Yin may treat sperm DNA damage through a multi-component, multi-target, and multi-pathway synergistic mechanism characterized by "antioxidation, mitochondrial stabilization, and apoptosis inhibition." This study provides a scientific basis for the clinical efficacy of Shenju Yin and indicates directions for further experimental validation.

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