Integrated analysis of Corylin from Psoralea Corylifolia inhibiting osteoporosis via MAPK pathway

Corylin, a natural flavonoid from Psoralea corylifolia (PC), has shown promise in the treatment of osteoporosis (OP) but the underlying mechanisms are unclear. This study aims to elucidate these mechanisms using network pharmacology, bioinformatics, molecular docking and in vitro experiments. Firstly, 213 potential therapeutic targets and 44 key targets were identified. Using the CytoHubba plugin, we screened the top 10 hub genes, including MMP9, BCL2, PPARG, PTGS2 and TNF, and others. Secondly, we identified that the MAPK, HIF-1, and Ras signaling pathways were highly enriched through enrichment analysis. The high enrichment of the MAPK pathway was further validated through transcriptomic analysis. Additionally, molecular dynamic simulation verified the formation of stable complexes between corylin and MMP9, PPARG, and PTGS2. Finally, we conducted in vivo and in vitro experiments to verify the effects of corylin on OP. In vitro, corylin (IC 50 = 10.79) significantly impaired cell proliferation, migration, and apoptosis. Western blot analysis revealed that the levels of P-MEK1/2, ATF1, P-JNK, P-ERK1/2, and BCL2 were significantly reduced, while Cleaved-Caspase3, PARP1, Bax, and Cleaved-Caspase7 were increased. Reverse Transcription quantitative Polymerase Chain Reaction (RT-qPCR) assays confirmed the upstream signals RANK/TRAF6, and p-MEK ELISA detection further validated the binding to MAPK pathway proteins. In vivo, corylin treatment ameliorated the deterioration of bone microarchitecture in an OP rat model. Additionally, corylin modulated serum bone turnover markers CTX-1 and P1NP. Overall, our findings demonstrate that corylin inhibits the MAPK pathway, inducing osteoclast apoptosis and identifying it as a promising therapeutic candidate for OP.