Qingre Huayu Granules ameliorate cerebral ischemic stroke via the PI3K/Akt signaling pathwayOA

Background:This study aimed to investigate the active ingredients,therapeutic targets,and potential biochemical mechanisms of Qingre Huayu Granules(QRHYKL)in treating cerebral ischemic stroke(CIS)based on network pharmacology,molecular docking,and animal experimental verification.Methods:Chemical components and target proteins of QRHYKL were obtained from the TCMSP,TCMID,PubChem databases,and literature retrieval,while targets related to CIS were obtained from the GeneCards and OMIM databases.The study compared information on pathological features of CIS and the targets of drugs to identify common elements.The data were imported into the STRING platform to generate a protein-protein interaction network diagram.Subsequently,a“component-target”network diagram was created using the screened drug components and target information with Cytoscape software.Common targets were imported into DAVID database for gene ontology(GO)function and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis.AutoDockTools was utilized to predict the molecular docking of the primary chemical components and core targets.molecular dynamics simulations were performed to assess the conformational stability and binding interactions of the protein-ligand complex.Finally,core targets of QRHYKL were validated through animal experiments.Results:Functional enrichment analysis revealed that key active ingredients of QRHYKL include baicalein,kaempferol,beta-sitosterol,Danshenol A,and salviolone.Core targets include TNF,IL-6,IL-1β,AKT1,CASP3,BCL-2,EGFR,and TP53.Potential therapeutic targets participate in biological processes such as inflammatory response,oxidative stress,and apoptosis,involving the AGE-RAGE signaling pathway,PI3K-Akt signaling pathway,and TNF signaling pathway.Animal experiments demonstrated that QRHYKL reduces neurological deficit scores,ameliorates neuronal pathological damage,decreases levels of inflammatory factors and oxidative stress response,inhibits PI3K-Akt protein expression,and alleviates neuronal apoptosis.Conclusion:QRHYKL may ameliorate cerebral ischemic injury,alleviate inflammation and oxidative stress,inhibit apoptosis,and exert cerebroprotective effects through multiple targets and signaling pathways.