Beyond nutrition effect, quercetin is applied as a complement or an alternative for promoting human health and treating diseases. However, its complicated neuroprotective mechanisms have not yet been fully elucidated. This study provides evidence of an alternative target for quercetin, and sheds light on the mechanisms of its neuroprotection against cerebral ischemia/reperfusion (I/R) injury in Sprague–Dawley rats. Oral pretreatment using quercetin has alleviated cerebral I/R-induced neurological deficits, brain infarction, blood–brain barrier disruption, oxidative stress, TNF-α and IL-1β mRNA expression, along with apoptotic caspase 3 activity. The neuroprotective, anti-oxidative, anti-inflammatory, and anti-apoptotic effects of quercetin were replicated in rat hippocampal slice cultures and neuron/glia cultures which suffered from oxygen–glucose deprivation and reoxygenation (OGDR). Biochemical studies revealed a reduction of extracellular signal-regulated kinase (ERK) and Akt phosphorylation, along with an increase in protein tyrosine and serine/threonine phosphatase activity in cerebral I/R rat cortical tissues and OGDR hippocampal slice and neuron/glia cultures. Quercetin alleviated the changes in ERK/Akt phosphorylation and protein phosphatase activities. Inhibition of ERK or Akt alone was enough to cause apoptotic cell death and cytotoxicity in hippocampal slice cultures and neuron/glia cultures, while activators of ERK or Akt alleviated OGDR-induced cytotoxicity. Taken together, our results demonstrate that quercetin alleviated the increment of protein tyrosine and serine/threonine phosphatase activity, along with the reduction of ERK and Akt phosphorylation, which may play pivotal roles in the expansion of brain injury after cerebral I/R.

除了营养作用外，槲皮素还可以作为补充或替代品来促进人类健康和治疗疾病。但是，其复杂的神经保护机制尚未完全阐明。这项研究提供了槲皮素替代靶点的证据，并阐明了其对Sprague-Dawley大鼠脑缺血/再灌注（I / R）损伤的神经保护机制。槲皮素的口服预处理减轻了脑I / R引起的神经功能缺损，脑梗塞，血脑屏障破坏，氧化应激，TNF-α和IL-1βmRNA表达以及凋亡的半胱天冬酶3活性。具有神经保护，抗氧化，消炎，槲皮素的抗凋亡作用和抗凋亡作用在遭受缺氧-葡萄糖剥夺和复氧（OGDR）的大鼠海马切片培养物和神经元/神经胶质培养物中复制。生化研究表明，脑I / R大鼠皮质组织，OGDR海马切片和神经元/神经胶质细胞培养物中细胞外信号调节激酶（ERK）和Akt磷酸化的减少，以及蛋白质酪氨酸和丝氨酸/苏氨酸磷酸酶活性的增加。槲皮素减轻了ERK / Akt磷酸化和蛋白磷酸酶活性的变化。单独抑制ERK或Akt足以在海马切片培养物和神经元/神经胶质培养物中引起凋亡细胞死亡和细胞毒性，而ERK或Akt的激活剂减轻了OGDR诱导的细胞毒性。在一起