Mechanisms of Aronia melanocarpa on cerebral ischemic injury based on network pharmacology and molecular docking
Objective To explore the specific components involved and underlying mechanisms of Aronia melanocarpa against cerebral ischemia.Methods SwissTargetPrediction and GeneCards databases was used to screen the blood-entry components and brain ischemia-related targets of A.melanocarpa.Gene ontology(GO)annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis was performed on the intersection targets using Metascape.The protein-protein interaction(PPI)network was constructed and analyzed using the STRING database and Cytoscape software.The interaction between the important components and targets were determined using molecular docking.Finally,the anti-cerebral ischemia effects of A.melanocarpa active component anthocyanin were evaluated using an in vivo model of rat permanent middle cerebral artery occlusion(pMCAO)and an in vitro model of cultured microglia subjected to oxygen-glucose deprivation(OGD).Results The network pharmacological analysis demonstrated that anthocyanin may serve as an effective component of A.melanocarpa in the treatment of cerebral ischemia.GO and KEGG enrichment analysis revealed that the TNF signaling pathway might be the main mechanism underlying the anti-cerebral ischemic effect of A.melanocarpa.Molecular docking results indicated a strong binding activity between anthocyanin and matrix metalloproteinases 2(MMP-2).The in vivo studies demonstrated that oral administration of anthocyanin(100,200 mg·kg-1)for seven consecutive days significantly ameliorated blood-brain barrier damage,downregulated the expression of MMP-2 and upregulated the levels of VE-cadherin and occluding as well as downregulated the expression of inflammatory cytokines interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),and inducible nitric oxide synthase(iNOS)at 24 h after cerebral ischemia in pMCAO-operated rats.In vitro experiments revealed that anthocyanins(20,60 pgmL-1)effectively reduced the nitrite content and attenuated the expression of inflammatory factors TNF-α,IL-1β,IL-6,and iNOs in OGD-treated BV2 microglia.Conclusion The extract of A.melanocarpa may contain anthocyanin as the active component against cerebral ischemia.Anthocyanin exhibits significant potential in mitigating blood-brain barrier damage and suppressing the release of inflammatory factors following permanent cerebral ischemia in rats.The present study provides an experimental foundation for further elucidating the active components,targets,and associated mechanisms underlying the anti-cerebral ischemic effects of A.melanocarpa and anthocyanin.
万方数据
