背景:卒中是世界范围内死亡和长期残疾的主要原因之一。以前的研究发现,corilagin具有抗氧化剂,抗炎,抗动脉粥样硬化等药理活性,对心脑血管损伤有保护作用。
目的:本研究的目的是研究corilagin对缺血性卒中的保护作用,并使用网络药理学阐明潜在的分子机制,分子对接,动物和细胞实验。
方法:我们使用体内大鼠大脑中动脉阻塞/再灌注(MCAO/R)和体外氧糖剥夺/复氧(OGD/R)模型研究了Corilagin改善脑缺血再灌注损伤的潜力。
结果:我们的结果表明,corilagin可能通过与92个关键靶点相互作用来发挥其抗缺血性卒中作用,包括凋亡相关蛋白(Bcl-2,Bax,caspase-3)和PI3K/Akt信号通路相关蛋白。体内和体外实验表明,corilagin治疗改善了神经功能缺损,减轻脑梗死体积,减轻MCAO/R大鼠的神经元损伤。Corilagin处理还增强了暴露于OGD/R的PC12细胞的存活,降低LDH泄漏率,抑制细胞凋亡,并激活PI3K/Akt信号通路。重要的是,Corilagin对PI3K/Akt信号通路和凋亡相关蛋白的作用被PI3K特异性抑制剂LY294002逆转.
结论:这些结果表明,Corilagin抗缺血作用的分子机制涉及抑制神经元凋亡和激活PI3K/Akt信号通路。这些发现为进一步开发和应用Corilagin作为潜在的抗缺血性卒中药物提供了理论和实验依据。
BACKGROUND: Stroke 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.
OBJECTIVE: The 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.
METHODS: We 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.
RESULTS: Our 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.
CONCLUSIONS: These 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.