Neuroprotection against cerebral ischemia/reperfusion by dietary phytochemical extracts from Tibetan turnip (Brassica rapa L.)

• Published in: Journal of ethnopharmacology Vol. 265; no. NA; p. 113410
• Main Authors: Hua, Hanyi, Zhang, Wenyi, Li, Jiaying, Li, Jiayi, Liu, Chang, Guo, Yahui, Cheng, Yuliang, Pi, Fuwei, Xie, Yunfei, Yao, Weirong, Gao, Yanqin, Qian, He
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 30.01.2021
• Subjects: Animals; Brain Ischemia - drug therapy; Brain Ischemia - pathology; Brassica rapa; Brassica rapa - chemistry; Brassica rapa L; Cell Line; cell viability; Cerebral ischemia/reperfusion; Disease Models, Animal; fluorescent antibody technique; infarction; Infarction, Middle Cerebral Artery; ischemia; lactate dehydrogenase; long term effects; Male; Mice; Mice, Inbred C57BL; mitochondria; Neuroprotection; Neuroprotective Agents - isolation & purification; Neuroprotective Agents - pharmacology; neuroprotective effect; Oncogene Protein v-akt - metabolism; Oriental traditional medicine; phosphatidylinositol 3-kinase; Phosphatidylinositol 3-Kinases - metabolism; phosphorylation; phytochemicals; PI3K/AkT/mTOR; Plant Extracts - pharmacology; reactive oxygen species; Reactive Oxygen Species - metabolism; Reperfusion Injury - drug therapy; Reperfusion Injury - pathology; stroke; Tibet; TOR Serine-Threonine Kinases - metabolism; turnips; Tibet; PI3K/AkT/mTOR; Brassica rapa L; Neuroprotection; Cerebral ischemia/reperfusion
• ISSN: 0378-8741; 1872-7573; 1872-7573
• DOI: 10.1016/j.jep.2020.113410

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. [Display omitted] •Aqueous extract of turnip (AET) inhibits hypoxia injury in vitro and vivo model.•AET recover the behavior and reduce the cerebral infarction volume in MCAO/R mice.•AET inhibits ROS, LDH production induced by oxygen glucose deprivation/reperfusion, and restore mitochondrial expression.•AET inhibit the apoptosis of HT-22 cells with OGD/R injury via activating PI3K/Akt/mTOR pathway.