Integrated network pharmacology, molecular docking and pharmacodynamic study reveals protective effects and mechanisms of corilagin against cerebral ischemia-induced injury

Abstract

BackgroundStroke is one of the leading causes of death and long-term disability worldwide. Previous studies have found that corilagin has antioxidant, anti-inflammatory, anti-atherosclerotic and other pharmacological activities and has a protective effect against cardiac and cerebrovascular injury. ObjectivesThe aim of this study was to investigate the protective effects of corilagin against ischemic stroke and to elucidate the underlying molecular mechanisms using network pharmacology, molecular docking, and animal and cell experiments. MethodsWe investigated the potential of corilagin to ameliorate cerebral ischemia–reperfusion injury using in vivo rat middle cerebral artery occlusion/reperfusion (MCAO/R) and in vitro oxygen–glucose deprivation/reoxygenation (OGD/R) models. ResultsOur results suggest that corilagin may exert its anti-ischemic stroke effect by interacting with 92 key targets, including apoptosis-associated proteins (Bcl-2, Bax, caspase-3) and PI3K/Akt signaling pathway-related proteins. In vivo and in vitro experiments showed that corilagin treatment improved neurological deficits, attenuated cerebral infarct volume, and mitigated neuronal damage in MCAO/R rats. Corilagin treatment also enhanced the survival of PC12 cells exposed to OGD/R, reduced the rate of LDH leakage, inhibited cell apoptosis, and activated the PI3K/Akt signaling pathway. Importantly, the effects of corilagin on the PI3K/Akt signaling pathway and apoptosis-associated proteins were reversed by the PI3K-specific inhibitor LY294002. ConclusionsThese results indicate that the molecular mechanism of the anti-ischemic effect of corilagin involves inhibiting neuronal apoptosis and activating the PI3K/Akt signaling pathway. These findings provide a theoretical and experimental basis for the further development and application of corilagin as a potential anti-ischemic stroke agent.