Astaxanthin alleviates cerebral infarction by targeting MAPK14: insights from network pharmacology, Molecular Docking, and experimental validation

Cerebral infarction (CI) is a serious cerebrovascular disease with high mortality, threatening patients’ lives and health. Astaxanthin (ATX) possesses exceptional antioxidant properties and exerts multiple protective effects in myocardial infarction. The present study aims to investigate the role and mechanism of ATX in the treatment of CI. The cell viability, proliferation, apoptosis, migration, and tube formation ability were detected by cell counting kit-8 (CCK8), ethynyl-2’-deoxyuridine (EdU) staining, flow cytometry, transwell assay, and tube formation assay, respectively. The levels of reactive oxygen species (ROS) and malondialdehyde (MDA) within the cells, as well as the activity of superoxide dismutase (SOD), were detected using corresponding specialized kits, respectively. Targets related to CI were screened by utilizing the GeneCard database. The potential pharmacological targets for ATX were forecasted through the Swiss Target Prediction (STP) database. The protein-protein interaction (PPI) network was constructed by the Search Tool for the Retrieval of Interacting Genes/Proteins database (STRING). The enrichment analyses for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were conducted by the Database for Annotation Visualization and Integrated Discovery 6.8 (DAVID 6.8). Gene expression was determined by western blot. Molecular docking was performed by AutoDock Vina software and visualized by Discovery Studio software and PyMOL software. Oxygen and glucose deprivation (OGD) inhibited the proliferation, migration, and tube formation abilities of human brain microvascular endothelial cells (HBMECs) and promoted cell apoptosis and oxidative stress responses, but the treatment with ATX alleviated these adverse effects. Mitogen-activated protein kinase 14 (MAPK14) stably bound to ATX and was identified as the potential target for ATX. The knockdown of MAPK14 mitigated the OGD-induced damage to HBMECs. ATX reduced OGD-induced damage to HBMECs by inhibiting the expression of MAPK14. ATX exerts an inhibitory effect to downregulate the expression level of MAPK14, thereby effectively mitigating the damage caused by OGD to HBMECs, and opening up a new avenue for the treatment of CI.