PTGS2 as a potential target for apigenin to promote spinal cord injury repair

Spinal cord injury (SCI) is characterized by damage to the spinal cord caused by various reasons, and there is a lack of effective drug treatments. Apigenin, a well-known natural small molecule drug, may serve as a therapeutic agent for a variety of diseases. However, the potential mechanisms by which Apigenin exerts its effects in SCI remain unclear. By utilizing an integrative multiomics strategy that combines network pharmacology, Mendelian randomization, and single-cell transcriptomic profiling, we established a systems-level target identification framework. Mechanistic analysis revealed a phytochemical‒neuropathy interactome, causal inference modeling (SMR) revealed target‒phenotype linkages and single-cell spatial mapping revealed the localization of target neural cell subtypes. In vitro experiments using PC12 cells and primary neuronal cells further validated the protective effects of apigenin against H2O2-induced neuronal injury. The results demonstrated that PTGS2, a key target identified through integrated analyses, exhibited elevated expression in SCI neurons. Apigenin treatment effectively mitigated H2O2-induced cellular damage while decreasing PTGS2 expression. These findings confirm that PTGS2 is a potential therapeutic target in SCI and highlight the value of a multiomics approach in overcoming traditional methodological limitations related to specificity and resolution. This study provides critical insights for advancing the clinical translation of apigenin and natural drug development strategies.