Abstract：
Cerebral ischemia-reperfusion injury (CI/RI) is a leading cause of disability and mortality worldwide, with limited therapeutic options available. Erianin, a natural compound derived from traditional Chinese medicine, has been reported to possess anti-inflammatory and neuroprotective properties. This study aimed to investigate the therapeutic potential of Erianin in CI/RI and elucidate its underlying mechanisms. Network pharmacology analysis predicted that Erianin could target the PI3K/AKT pathway, which are closely associated with CI/RI. In vivo experiments using a rat model of CI/RI demonstrated that Erianin treatment significantly alleviated neurological deficits, reduced infarct volume, and attenuated neuronal damage. Mechanistically, Erianin inhibited microglial cell polarization towards the pro-inflammatory M1 phenotype, as evidenced by the modulation of specific markers. Furthermore, Erianin suppressed the expression of pro-inflammatory cytokines and mediators, such as TNF-α, IL-6, and COX-2, while enhancing the production of anti-inflammatory factors, including Arg1, CD206, IL-4 and IL-10. In vitro studies using oxygen-glucose deprivation/reoxygenation (OGD/R)-stimulated microglial cells corroborated the anti-inflammatory and anti-apoptotic effects of Erianin. Notably, Erianin inhibited the NF-κB signaling pathway by inhibiting p65 phosphorylation and preventing the nuclear translocation of the p65 subunit. Collectively, these findings suggest that Erianin represents a promising therapeutic candidate for CI/RI by targeting microglial cell polarization and inflammation.
摘要：
脑缺血再灌注损伤(CI/RI)是全球范围内致残和死亡的主要原因,有限的治疗选择。Erianin,一种来自中药的天然化合物，据报道具有抗炎和神经保护特性。本研究旨在探讨Erianin在CI/RI中的治疗潜力并阐明其潜在机制。网络药理学分析预测Erianin可以靶向PI3K/AKT通路，与CI/RI密切相关。使用CI/RI大鼠模型的体内实验表明，Erianin治疗可显着减轻神经功能缺损，梗死体积减少,减轻神经元损伤。机械上,Erianin抑制小胶质细胞向促炎M1表型极化，由特定标记的调制证明。此外，Erianin抑制促炎细胞因子和介质的表达，如TNF-α，IL-6和COX-2，同时增强抗炎因子的产生，包括Arg1、CD206、IL-4和IL-10。使用氧-葡萄糖剥夺/复氧（OGD/R）刺激的小胶质细胞的体外研究证实了Erianin的抗炎和抗凋亡作用。值得注意的是,Erianin通过抑制p65磷酸化和阻止p65亚基的核易位来抑制NF-κB信号通路。总的来说，这些研究结果表明,Erianin通过靶向小胶质细胞极化和炎症,成为CI/RI的有希望的治疗候选药物.
