[Study on the therapeutic mechanism of Shenshu Yijing Formula in treating obesity-related male infertility using a combination of UPLC-Q/TOF-MS, network pharmacology and molecular docking technology].

Abstract

Objective The aim of this study is to identify the key effective components of the Shenshu Yijing Formula (SZYJF) and to explore its therapeutic mechanism against obesity-related male infertility (ORMI) by integrating ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF-MS), network pharmacology and molecular docking technology. MethodsUPLC-Q/TOF-MS was used to determine the primary active components of SZYJF. The target proteins of these components were retrieved from the Swiss Target Prediction database. Disease-related targets for obesity and male infertility were obtained from Genecards, OMIM and the Traditional Chinese Medicine Integrated Database (TCMID). Overlapping targets between SZYJF and diseases were identified. A protein-protein interaction (PPI) network was constructed using the STRING platform. GO and KEGG pathway analysis were performed using R software. A drug-component-target-pathway network was visualized with Cytoscape. And molecular docking validation was conducted using PyMOL and AutoDock Vina. Animal experiments were performed to validate the findings. Results UPLC-Q/TOF-MS identified 245 active components in SZYJF, with 34 prioritized based on pharmacological properties, corresponding to 199 targets. A total of 117 overlapping targets were mapped to obesity and infertility. Biological processes included responses to external stimuli, lipid metabolic processes and hypoxia. Enriched pathways included the AGE-RAGE signaling pathway in diabetic complications, TNF signaling, Toll-like receptor (TLR) signaling, NOD-like receptor (NLR) signaling and adiponectin signaling. Molecular docking confirmed strong binding affinity between target proteins and active components. Animal experiments had found that SZYJF has a positive effect on improving sperm concentration and sperm motility in obese reproductive injury model mice, and the mechanism may involve regulating the expression of IGF-1/IRS-2/CLU proteins to exert protective effects on fertility. Conclusion SZYJF exerts a multi-target, multi-pathway mechanism against ORMI by modulating aberrant protein expression, alleviating oxidative stress in mice, and preserving fertility.

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