基于网络药理学策略预测并体外验证银杏内酯B的潜在适应证OA

Objective:To predict potential indications for ginkgolide B(GB)based on network pharmacology strategies.Methods:GB targets were comprehensively identified by integrating data from the Therapeutic Target Database,the Comparative Toxicogenomics Database,and BindingDB,followed by further validation based on literature.A standardized disease-gene dataset was established by integrating data from the genome-wide association study and the Online Mendelian Inheritance in Man Database.The topological proximity between GB targets and disease modules within the human protein-protein interaction network was quantified using network proximity metrics,with statistical significance evaluated via Z-score and permutation testing(Z<0,P<0.05).Candidate diseases were classified according to MeSH terms,visualized through network mapping,and further characterized by gene set similarity based on the Jaccard index.Experiments in RAW 264.7 macrophages were conducted to validate the inhibitory effect of GB on nitric oxide and proinflammatory cytokines.Results:Twelve potential GB targets were identified,and a disease-gene dataset encompassing 680 diseases was established.Network proximity analysis revealed significant associations between GB and 22 diseases,of which 11 had prior literature support.Disease classification indicated that the predicted indications of GB were primarily enriched in immune-mediated inflammatory diseases,with notable examples including juvenile idiopathic arthritis(Z=-3.10)and Crohn disease(Z=-3.05).Network analysis suggested that GB may exert pleiotropic regulatory effects across multiple diseases via key targets such as MAPK1.The strongest gene set similarity was observed between juvenile idiopathic arthritis and ankylosing spondylitis(Jaccard index=0.60).In vitro experiments with macrophages demonstrated that GB suppresses the production of nitric oxide and proinflammatory cytokines,thereby supporting its potential as a therapeutic agent for immune-mediated inflammatory diseases.Conclusion:This study systematically predicted 22 potential indications for GB and confirmed its therapeutic potential for immune-mediated inflam-matory diseases through in vitro experiments.