Neuroprotection against cerebral ischemia/reperfusion by dietary phytochemical extracts from Tibetan turnip (Brassica rapa L.)
Neuroprotection against cerebral ischemia/reperfusion by dietary phytochemical extracts from Tibetan turnip (Brassica rapa L.)
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DOI：
10.1016/j.jep.2020.113410
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发表时间：
2021-01-30
影响因子：
5.4
通讯作者：
Qian, He
中科院分区：
文献类型：
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作者：
Hua, Hanyi;Zhang, Wenyi;Qian, He
民族药理学相关性：西藏萝卜（Brassica rapa L.）具有清热、解毒、抗缺氧等多种药用功效，载入百年藏医名著《四大医续》。循证医学还表明萝卜具有抗缺氧作用，这表明其与缺血性中风的神经保护作用存在潜在联系。这使得芜菁可以作为一种新型无毒药物用于相关治疗。研究目的：本研究旨在探讨芜菁水提取物（AET）对脑缺血/再灌注的神经保护作用并阐明其机制。材料和方法：脑缺血实验模型包括C57BL/6J小鼠短暂性大脑中动脉闭塞/再灌注（MCAO）和氧糖剥夺/复氧(OGD/R) 在 HT-22 细胞中。 MCAO 后 28 天通过微管相关蛋白 2 (MAP2) 免疫荧光评估 AET 对梗塞体积的长期影响，同时通过旋转棒、网格行走和圆柱体测试确定神经功能结果。 AET 的功效取决于细胞活力、神经元中乳酸脱氢酶 (LDH) 和活性氧 (ROS) 的释放。 AET拯救OGD/R细胞的潜在机制以PI3K、Akt和mTOR表达为特征，进一步用于验证AET在该通路中的作用。结果：AET可以剂量依赖性地减少脑梗塞体积并改善MCAO/R小鼠的行为缺陷。体外实验进一步证明，合适浓度的AET可抑制ROS、LDH的产生并恢复OGD/R诱导的线粒体表达。 AET预处理可以逆转OGD/R诱导的PI3K、Akt、mTOR磷酸化水平下降，而LY294002（PI3K抑制剂）治疗组阻断了这种作用。结论：AET通过激活PI3K/Akt/mTOR通路提高OGD/R损伤的HT-22细胞的存活率。综上所述，萝卜水提取物对局灶性脑缺血损伤具有保护作用。
Ethnopharmacological relevance: The Tibetan turnip (Brassica rapa L.) has a wide array of medicine properties including heat-clearing, detoxifying and anti-hypoxia as listed in the famous centuries-old Tibetan medicine classic "The Four Medical Tantras". Evidence-based medicine also indicated the anti-hypoxic effect of turnips, suggesting a potential link to neuroprotective effect on ischemic stroke. This thereby enables turnips to serve as a novel nontoxic agent in related treatment.Aim of the study: This study aimed to investigate the neuroprotective effect and elucidate the mechanism of aqueous extract of turnip (AET) on cerebral ischemia/reperfusion.Materials and methods: The experimental models of cerebral ischemia included transient middle cerebral artery occlusion/reperfusion (MCAO) in C57BL/6J mice and oxygen-glucose deprivation/reoxygenation (OGD/R) in HT-22 cells. Long-term effect of AET on infarct volume was evaluated by microtubule-associated protein 2 (MAP2) immunofluorescence 28 days after MCAO, and on neurofunctional outcomes determined by rotarod, grid walking, and cylinder tests in the meantime. Efficacy of AET was determined by the cell viability, the release of lactate dehydrogenase (LDH) and reactive oxygen species (ROS) in neurons. The underlying mechanism of AET rescued OGD/R cells were characterized by PI3K, Akt and mTOR expressions, which were further used to validate AET's role in the pathway.Results: AET can reduce cerebral infarct volume and ameliorate behavioral deficits of MCAO/R mice dose-dependently. In vitro experiment further demonstrated that suitable concentrations of AET inhibited ROS, LDH production and restored mitochondrial expression induced by OGD/R. AET pretreatment can reverse the OGD/R-induced decreased level of phosphorylation of PI3K, Akt, mTOR, whereas this effect was blocked in the LY294002 (PI3K inhibitor) treatment group.Conclusions: AET improved the survival of OGD/R-injured HT-22 cells by activating the PI3K/Akt/mTOR pathway. Based on the results above, aqueous extract of turnip has a protective effect on focal cerebral ischemic injury.