Department of School of Food Science and Technology, Jiangnan University, Wuxi, 214122, China.
State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, Shanghai, 200032, China.
J Ethnopharmacol. 2021 Jan 30;265:113410. doi: 10.1016/j.jep.2020.113410. Epub 2020 Sep 24.
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.
This study aimed to investigate the neuroprotective effect and elucidate the mechanism of aqueous extract of turnip (AET) on cerebral ischemia/reperfusion.
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.
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.
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.
藏萝卜（Brassica rapa L.）具有广泛的药用特性，包括清热、解毒和抗缺氧，这些特性在著名的几个世纪前的藏药经典《四部医典》中均有记载。循证医学也表明萝卜具有抗缺氧作用，这表明其可能对缺血性中风具有神经保护作用。这使得萝卜成为相关治疗的一种新型无毒药物。
本研究旨在探讨藏萝卜水提物（AET）对脑缺血/再灌注的神经保护作用及其机制。
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 HT-22 细胞氧葡萄糖剥夺/再氧合（OGD/R）。通过 MCAO 后 28 天的微管相关蛋白 2（MAP2）免疫荧光评估 AET 对梗死体积的长期影响，同时通过转棒、网格行走和圆筒试验评估 AET 对神经功能结果的影响。通过神经元活力、乳酸脱氢酶（LDH）和活性氧（ROS）的释放来确定 AET 的疗效。通过 PI3K、Akt 和 mTOR 的表达来表征 AET 拯救 OGD/R 细胞的作用机制，进一步用于验证 AET 在该通路中的作用。
AET 可剂量依赖性地减少 MCAO/R 小鼠的脑梗死体积并改善其行为缺陷。体外实验进一步表明，合适浓度的 AET 可抑制 OGD/R 引起的 ROS、LDH 产生和线粒体表达的降低。AET 预处理可以逆转 OGD/R 诱导的 PI3K、Akt、mTOR 磷酸化水平的降低，但在 LY294002（PI3K 抑制剂）处理组中，这种作用被阻断。
AET 通过激活 PI3K/Akt/mTOR 通路改善了 OGD/R 损伤的 HT-22 细胞的存活。基于上述结果，藏萝卜水提物对局灶性脑缺血损伤具有保护作用。
