Mechanisms of polydatin against spinal cord ischemia–reperfusion injury based on network pharmacology, molecular docking and molecular dynamics simulation

Polydatin has shown considerable pharmacological activities in ischemia–reperfusion injuries of various organs. However, its effects and mechanisms in spinal cord ischemia–reperfusion injury have not been fully established. In this study, the mechanisms of polydatin against spinal cord ischemia–reperfusion injury were investigated via network pharmacology, molecular docking and molecular dynamics simulation. Spinal cord ischemia–reperfusion injury-related targets were obtained from the GeneCards database, while polydatin-related action targets were obtained from the CTD and SwissTarget databases. A protein–protein interaction network of potential targets was constructed using the String platform. After selecting the potential key targets, GO functional enrichment and KEGG pathway enrichment analyses were performed via the Metascape database, and a network map of "drug-target-pathway-disease" constructed. The relationships between polydatin and various key targets were assessed via molecular docking. Molecular dynamics simulation was conducted for optimal core protein–compound complexes obtained by molecular docking. Topological analysis of the PPI network revealed 14 core targets. GO functional enrichment analysis revealed that 435 biological processes, 12 cell components and 29 molecular functions were enriched while KEGG pathway enrichment analysis revealed 91 enriched signaling pathways. Molecular docking showed that polydatin had the highest binding affinity for MAPK3, suggesting that MAPK3 is a key target of polydatin against spinal cord ischemia–reperfusion injury. Molecular dynamics simulations revealed good binding abilities between polydatin and MAPK3. Polydatin exerts its effects on spinal cord ischemia–reperfusion injury through multiple targets and pathways. MAPK3 may be a key target of polydatin in spinal cord ischemia–reperfusion injury.