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The underlying mechanisms of Oxysophocarpine (OSC) in Cerebral Ischemia (CI) treatment were investigated through network pharmacology, molecular docking, and in vitro experiments.
The potential targets of OSC were predicted using the PubChem, SwissTargetPrediction, and PharmMapper databases. Relevant CI targets were identified through the GeneCards and Online Mendelian Inheritance in Man (OMIM) databases, and common targets between OSC and cerebral ischemia were determined using Venny2.1.0. Drug-disease Protein-Protein Interaction (PPI) networks were analyzed using the String database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of key targets were conducted using the DAVID database. Molecular docking verification was performed using Autodock Vina. The results of the network pharmacological analysis were validated through in vitro experiments.
Mapping the drug and disease targets yielded 126 common targets. GO and KEGG enrichment analysis revealed that OSC's therapeutic mechanism in CI involves multiple pathways, including those related to cancer, MAPK signaling, and PI3K-Akt signaling. Molecular docking results demonstrated strong binding activity of OSC to core protein targets. In vitro experiments indicated that OSC enhances the survival rate of four hours of sugar deprivation and 12 hours of reoxygenation (OGD4h/R12h) in bEnd.3 cells and reduces the protein expression of p-PI3K and p-Akt.
The “multi-target and multi-mechanism” actions of OSC in CI treatment were elucidated through network pharmacology and molecular docking, providing a scientific basis for further investigation.
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