Objective  To investigate the molecular mechanism of Gardeniae Fructus regulating ferroptosis in the treatment of cerebral ischemia-reperfusion injury (CIRI) by network pharmacology methods.

Methods  The effective active ingredients of Gardeniae Fructus and their predicted targets were obtained from the TCMSP database. Cerebral ischemia-reperfusion injury were collected and obtained from the GeneCards database. The active ingredients of Gardeniae Fructus and the intersection genes of CIRI injury were obtained through Venny. The Cytoscape 3.9.1 software was utilized to construct a relationship network among Gardeniae Fructus, its active components and predicted targets. The gene ontology (GO) enrichment and the Kyoto encyclopedia of genes and genomes (KEGG) analyses of the "gardenia-CIRI" intersection genes were performed using R software. The ferroptosis-related genes were obtained from the FerrDb database, and the common targets among the active components of Gardeniae Fructus, CIRI and ferroptosis were comprehensively analyzed to predict the effective components and targets involved in the regulation of ferroptosis in the context of CIRI.

Results  Sixty-five active components with corresponding gene targets were identified from Gardeniae Fructus, and the correlating prediction was conducted. HIF-1α, TP53, MAPK8, HMOX1, NOS2, RELA  and IL-6 were identified as potential targets of Gardeniae Fructus in regulating ferroptosis and preventing cerebral ischemia-reperfusion injury. KEGG analysis suggested that Gardeniae Fructus may mediate HIF-1, TNF, MAPK and Toll-like receptor signaling pathways to regulate the ferroptosis process, thus exerting therapeutic effects on CIRI.

Conclusion Gardeniae Fructus may treat cerebral ischemia-reperfusion injury by regulating the ferroptosis pathway.

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