Luteoloside attenuates neuroinflammation in focal cerebral ischemia in rats via regulation of the PPARγ/Nrf2/NF-κB signaling pathway
Luteoloside attenuates neuroinflammation in focal cerebral ischemia in rats via regulation of the PPARγ/Nrf2/NF-κB signaling pathway
复制标题
木犀草苷通过调节 PPAR gamma/Nrf2/NF-kappa B 信号通路减轻大鼠局灶性脑缺血的神经炎症
DOI：
10.1016/j.intimp.2018.11.044
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发表时间：
2019-01-01
影响因子：
5.6
通讯作者：
Pang, Xiaobin
中科院分区：
文献类型：
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作者：
Li, Qiaoling;Tian, Zixia;Pang, Xiaobin
木犀草苷是一种黄酮类化合物，具有抗炎、抗氧化、抗菌、抗病毒、抗癌、心脏保护等作用，但对其神经保护作用的研究较少。本研究旨在观察木犀草苷对脑缺血的保护作用，并探讨其可能的机制。采用大鼠大脑中动脉闭塞(MCAO)模型，观察木犀草素对脑缺血再灌注(I/R)的影响。雄性SD大鼠随机分为假手术组、MCAO组、黄体素(20 mg/kg、40 mg/kg、80 mg/kg)组和尼莫地平(4 mg/kg)组。结果表明，木犀草素可减轻MCAO大鼠的神经功能缺失和脑水肿，改善脑梗塞和组织病理学改变。木犀草苷显著抑制脑缺血再灌注所致的神经炎症反应，表现为脑组织中IL-1β、肿瘤坏死因子-α、诱导型一氧化氮合酶(INOS)和环氧合酶-2(COX-2)水平的降低。此外，我们的结果表明，木犀草苷显著抑制了核因子-kappaB(NF-kappa B)信号的激活，上调了PPAR-γ的蛋白表达，并增加了核因子-E2相关因子(Nrf2)的核积聚。综上所述，我们的研究结果表明，木犀草苷通过抑制大鼠局灶性脑缺血中的核因子-kappaB信号，发挥了重要的神经保护作用。此外，PPAR-γ和Nrf2在木犀草苷的抗炎作用中也起重要作用。此外，我们的数据表明，木犀草苷可能是治疗脑缺血和其他神经疾病的有效药物。
Luteoloside, a flavonoid compound, has been reported to have anti-inflammatory, anti-oxidative, antibacterial, antiviral, anticancer, and cardioprotective effects, among others, but its neuroprotective effects have rarely been studied. The purpose of this study was to investigate the protective effect of luteoloside on cerebral ischemia and explore its potential mechanism. Middle cerebral artery occlusion (MCAO) was performed to investigate the effects of luteoloside on cerebral ischemia-reperfusion (I/R). Male Sprague-Dawley rats were randomly divided into six groups: sham, MCAO, luteoloside (20 mg/kg, 40 mg/kg, 80 mg/kg) and nimodipine (4 mg/kg). The results showed that luteoloside alleviated neurologic deficits and cerebral edema as well as improved cerebral infarction and histopathological changes in MCAO rats. Luteoloside significantly inhibited I/R-induced neuroinflammation, as demonstrated by reduced levels of interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in the brain tissues of MCAO rats. Furthermore, our results demonstrated that luteoloside significantly suppressed the activation of nuclear factorkappa B (NF-kappa B) signaling, upregulated the protein expression of peroxisome proliferator activated receptor gamma (PPAR gamma) and increased NF-E2-related factor (Nrf2) nuclear accumulation in MCAO rats. Collectively, our findings suggested that luteoloside played a crucial neuroprotective role by inhibiting NF-kappa B signaling in focal cerebral ischemia in rats. Furthermore, PPAR gamma and Nrf2 were also important for the anti-inflammatory effect of luteoloside. In addition, our data suggested that luteoloside might be an effective treatment for cerebral ischemia and other neurological disorders.