Abstract：
Ischemia-reperfusion (I/R) injury is a key influencing factor in the outcome of stroke. Inflammatory response, oxidative stress, and neuronal apoptosis are among the main factors that affect the progression of I/R injury. Farrerol (FAR) is a natural compound that can effectively inhibit the inflammatory response and oxidative stress. However, the role of FAR in cerebral I/R injury remains unknown. In this study, we found that FAR reduced brain injury and neuronal viability after cerebral I/R injury. Meanwhile, administration of FAR also reduced the inflammatory response of microglia after brain injury. Mechanistically, FAR treatment directly reduced neuronal death after oxygen glucose deprivation/re-oxygenation (OGD/R) through enhancing cAMP-response element binding protein (CREB) activation to increase the expression of downstream neurotrophic factors and anti-apoptotic genes. Moreover, FAR decreased the activation of nuclear factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways, inhibited microglia activation, and reduced the production of inflammatory cytokines in microglia after OGD/R treatment or LPS stimulation. The compromised inflammatory response by FAR directly promoted the survival of neurons after OGD/R. In conclusion, FAR exerted a protective effect on cerebral I/R injury by directly decreasing neuronal death through upregulating CREB expression and attenuating neuroinflammation. Therefore, FAR could be a potentially effective drug for the treatment of cerebral I/R injury.
摘要：
缺血再灌注(I/R)损伤是影响脑卒中预后的关键因素。炎症反应，氧化应激，神经元凋亡是影响I/R损伤进展的主要因素。Farrarrol（FAR）是一种天然化合物，可以有效抑制炎症反应和氧化应激。然而,FAR在脑I/R损伤中的作用尚不清楚。在这项研究中,我们发现FAR可以降低I/R损伤后的脑损伤和神经元活力。同时,FAR的给药也降低了脑损伤后小胶质细胞的炎症反应。机械上,FAR治疗通过增强cAMP反应元件结合蛋白（CREB）的激活来增加下游神经营养因子和抗凋亡基因的表达，从而直接减少氧糖剥夺/复氧（OGD/R）后的神经元死亡。此外，FAR降低核因子κB(NF-κB)和丝裂原活化蛋白激酶(MAPK)信号通路的激活,抑制小胶质细胞激活，并减少OGD/R处理或LPS刺激后小胶质细胞中炎性细胞因子的产生。FAR受损的炎症反应直接促进OGD/R后神经元的存活。总之,FAR通过上调CREB表达和减轻神经炎症直接减少神经元死亡，对脑I/R损伤具有保护作用。因此,FAR可能是治疗脑I/R损伤的潜在有效药物。
