人参皂苷调节髋关节置换术后纤溶平衡的网络药理学与代谢组学分析

Total hip arthroplasty (THA) is an effective treatment for end‑stage hip disease. However, postoperative fibrinolytic imbalance is common and increases the risks of bleeding and thrombosis. Ginsenosides, the main active constituents of Panax ginseng , exhibit multiple pharmacological activities, including anti‑inflammatory and anti‑apoptotic effects. Nevertheless, their role in fibrinolytic balance after THA remains unclear. Ginsenoside active components were screened from databases such as TCMSP and BATMAN-TCM and further filtered based on ADME parameters. Key targets were obtained via network pharmacology, and a protein–protein interaction (PPI) network was constructed. GO and KEGG enrichment pathway analyses were performed. Venous blood samples were collected from the same patient undergoing THA at 2 h before and 24 h after surgery and subjected to untargeted metabolomics analysis by LC-MS/MS. Multivariate statistical analysis was used to screen differential metabolites and perform pathway enrichment. By integrating network pharmacology and metabolomics results, a “component–target–metabolic pathway” association network was constructed. In vitro validation was performed using techniques such as qRT-PCR and Western blot. A total of nine active ginsenoside components were screened, yielding 351 component targets and 428 fibrinolysis-related targets. Sixty-five key targets were obtained by intersection. PPI network analysis identified AKT1, PTGS2, JUN, and others as core targets. KEGG enrichment analysis showed significant enrichment of complement and coagulation cascades, platelet activation, and the HIF-1 signaling pathway. Metabolomics identified 292 differential metabolites, mainly enriched in pathways such as arachidonic acid metabolism, purine metabolism, and glycerophospholipid metabolism. Based on VIP scores, the top 20 differential metabolites were subjected to exploratory correlation analysis with changes in hemoglobin and platelet counts before and after surgery. Adenosine, sphingosine, and arachidonic acid were positively correlated with changes in hemoglobin and platelet counts. Integrated analysis revealed that arachidonic acid metabolism, cGMP-PKG, cAMP, and sphingolipid signaling pathways were common key pathways. Molecular docking was performed between the core target AKT1 and ginsenoside Rh7, JUN and ginsenoside Rg3, PIK3CA and ginsenoside Rh1, and PTGS2 and ginsenoside F2. The results showed good binding affinity. Further qRT-PCR and Western blot (WB) experiments showed that in LPS-stimulated venous endothelial cells (VECs), intervention with ginsenosides Rh7, Rg3, Rh1, and F2 significantly inhibited the mRNA and protein expression levels of AKT1, JUN, PIK3CA and PTGS2, respectively. WB analysis further revealed that Rh7 intervention in LPS-stimulated VECs significantly promoted the expression of tissue-type plasminogen activator (t-PA) and reduced the expression of plasminogen activator inhibitor-1 (PAI-1). These findings further suggest that ginsenoside Rh7 may affect fibrinolytic balance after total hip arthroplasty. This study explored the possibility that ginsenosides Rh7, Rg3, Rh1, and F2 may affect multiple pathways, such as arachidonic acid metabolism and the complement and coagulation cascades, by regulating targets including AKT1, PTGS2, JUN, and PIK3CA. Among them, ginsenoside Rh7 may improve fibrinolytic balance after THA, providing a theoretical basis for its perioperative clinical application.