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

DENG Yingjun; LIU Shengjing; ZHAO Feng; LIU Qi; YAN Bin; YU Wenxiao; GUO Jun

doi:10.13263/j.cnki.nja.2026.01.008

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-perform-ance liquid chromatography quadrupole time-of-flight mass spectrometry(UPLC-Q/TOF-MS),network pharmacology and molec-ular docking technology.Methods UPLC-Q/TOF-MS was used to determine the primary active components of SZYJF.The tar-get 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.Ani-mal 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 re-ceptor(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 regu-lating 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.