Biochanin A Provides Neuroprotection Against Cerebral Ischemia/Reperfusion Injury by Nrf2-Mediated Inhibition of Oxidative Stress and Inflammation Signaling Pathway in Rats
Biochanin A Provides Neuroprotection Against Cerebral Ischemia/Reperfusion Injury by Nrf2-Mediated Inhibition of Oxidative Stress and Inflammation Signaling Pathway in Rats
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Biochanin A 通过 Nrf2 介导的抑制大鼠氧化应激和炎症信号通路提供针对脑缺血/再灌注损伤的神经保护。
DOI：
10.12659/msm.918665
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发表时间：
2019-11-26
影响因子：
3.1
通讯作者：
Wang, Yong
中科院分区：
文献类型：
--
作者：
Guo, Minmin;Lu, Huiling;Wang, Yong
背景：氧化应激和神经炎症是脑缺血再灌注损伤进展的两个关键机制。生物茶素A是一种天然的植物雌激素，在动物实验中已被报道对缺血性脑损伤有保护作用，但其神经保护的可能药理机制尚不清楚。在这项研究中，我们试图研究生物茶素A对实验性中风大鼠的神经保护作用，以及氧化应激和炎症信号通路的可能机制。材料/方法：采用脑中动脉穿刺术建立缺血性脑卒中模型。大鼠预先腹腔注射载药溶液或生物链素a（10、20或40 mg.kg）。D(-1))在缺血性脑卒中前14天。在缺血2小时和再灌注24小时后评估神经学评分、梗死体积和脑水肿。测定SOD、GSH-Px活性及MDA含量。Western blotting检测Nrf2、HO-1、NE-kappa B的表达及磷酸化- i kappa B α的活性。结果：生物茶素A预处理可显著改善神经功能缺损，减少梗死面积和脑水肿。生物茶素A还能提高SOD和GSH-Px活性，抑制MDA的产生。此外，生物茶素A在缺血性脑损伤中促进Nrf2核易位，促进HO-1的表达，抑制NE-kappa B的激活。结论：生物茶素A具有抗氧化和抗炎作用，对大鼠脑缺血损伤具有保护作用。激活Nrf2通路和抑制NE-kappa B通路可能有助于生物茶素A的神经保护作用。
Background: Oxidative stress and neuroinflammation are 2 pivotal mechanisms in the progression of cerebral ischemia/reperfusion injury. Biochanin A, a natural phytoestrogen, has been reported to protect against ischemic brain injury in animal experiments, but the possible pharmacological mechanisms of its neuroprotection remain elusive. In this research, we sought to investigate the neuroprotective effects of biochanin A in experimental stroke rats and the probable mechanisms underlying oxidative stress and inflammation signaling pathways.Material/Methods: An ischemic stroke model was induced by inserting thread into the middle cerebral artery. Rats were pre-administered intraperitoneally with a vehicle solution or biochanin A (10, 20, or 40 mg.kg.d(-1)) for 14 days prior to ischemic stroke. Neurological score, infarct volume, and cerebral edema were assessed after 2 h of ischemia and 24 h of reperfusion. The activities of SOD and GSH-Px and MDA content were measured. The expressions of Nrf2, HO-1, and NE-kappa B and the activity of phosphor-I kappa B alpha were detected by Western blotting.Results: Biochanin A pretreatment significantly improved neurological deficit and decreased infarct size and brain edema. Biochanin A also enhanced SOD and GSH-Px activities and suppressed the production of MDA. Additionally, biochanin A promoted Nrf2 nuclear translocation, promoted the expression of HO-1, and inhibited NE-kappa B activation in ischemic brain injury.Conclusions: The results indicated that biochanin A protected the brain against ischemic injury in rats by anti-oxidative and anti-inflammatory actions. The activation of the Nrf2 pathway and the inhibition of the NE-kappa B pathway may contribute to the neuroprotective effects of biochanin A.