Protective effect of Jinkui Shenqi pills against polystyrene-induced reproductive injury

Objective: Polystyrene exposure poses an increasing threat to reproductive health, and effective interventions remain limited. Jinkui Shenqi pills (JSP), a traditional Chinese medicine used to treat reproductive disorders, may protect against such damage. This study integrated network pharmacology with experimental validation to explore the mechanisms by which JSP counteracts polystyrene-induced reproductive toxicity. Methods: Potential targets related to polystyrene toxicity and bioactive components of JSP were retrieved from relevant databases. Overlapping targets were identified using VENNY 2.1. Protein-protein interaction networks were constructed using STRING, and core targets were identified with Cytoscape. Enrichment analyses were performed using DAVID. Molecular docking was used to evaluate ligand-target binding. A polystyrene-exposed mouse model was established, and tissue injury and recovery were assessed by hematoxylin-eosin (HE) staining and Western blotting (WB). Results: In-depth screening identified 111 overlapping targets, and three key molecules-AKT serine/threonine kinase 1 (AKT1), caspase-3 (CASP3), and B-cell lymphoma 2 (BCL2)-were selected for further investigation. Gene Ontology analysis highlighted phosphorylation-related processes and responses to xenobiotics, while Kyoto Encyclopedia of Genes and Genomes analysis indicated enrichment in pathways related to lipid metabolism, atherosclerosis, cancer, and phosphatidylinositol-3-kinase (PI3K)-AKT signaling. Molecular docking confirmed effective binding of sitosterol, alisol B monoacetate, acetate, and alisol to these targets. HE staining revealed polystyrene-induced damage in testicular and ovarian tissues, which was effectively alleviated by JSP administration. WB results further demonstrated that JSP upregulated the expression of core target proteins, supporting its protective role against polystyrene-induced reproductive toxicity. Conclusion: JSP mitigates polystyrene-induced reproductive toxicity by modulating AKT1, CASP3, and BCL2, supporting its potential as a protective agent.