Cannabidiol attenuates OGD/R-induced damage by enhancing mitochondrial bioenergetics and modulating glucose metabolism via pentose-phosphate pathway in hippocampal neurons.
Cannabidiol attenuates OGD/R-induced damage by enhancing mitochondrial bioenergetics and modulating glucose metabolism via pentose-phosphate pathway in hippocampal neurons.
复制标题
大麻二酚通过增强线粒体生物能并通过海马神经元中的戊糖磷酸途径调节葡萄糖代谢来减轻 OGD/R 诱导的损伤
DOI：
10.1016/j.redox.2016.12.029
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发表时间：
2017-04
期刊：
影响因子：
11.4
通讯作者：
Zhang S
中科院分区：
文献类型：
--
作者：
Sun S;Hu F;Wu J;Zhang S
缺乏生物能量学和氧化还原保守性减弱参与了脑缺血/再灌注损伤的发生发展。在这项研究中，大麻二酚(CBD)是一种从大麻中提取的具有FDA批准的抗癫痫活性的非精神药物化合物，本研究利用小鼠海马神经细胞系的缺氧-葡萄糖剥夺/再灌注(OGD/R)模型，在体外研究了大麻二醇(CBD)的神经保护作用机制。再灌流期间补充CBD可减轻OGD/R诱导的细胞死亡，减少细胞内ROS生成和脂质过氧化，同时逆转抗氧化生物标志物的异常变化。使用海马氏XFe24细胞外通量分析仪，我们发现CBD显著改善了OGD/R损伤神经元的基础呼吸、ATP相关的耗氧率和备用呼吸量，并增加了葡萄糖消耗。葡萄糖6-磷酸脱氢酶的激活和NADPH/NADP+比值的保持表明CBD刺激了戊糖-磷酸途径，从而保护海马神经元免受OGD/R损伤。本研究首次证明CBD对OGD/R损伤的神经保护作用，部分依赖于减轻氧化应激，增强线粒体生物能量学，并通过戊糖-磷酸途径调节葡萄糖代谢，从而维持能量和氧化还原平衡。大麻二酚对OGD/R诱导的海马神经元氧化应激的保护作用大麻二酚增强线粒体生物能量学。大麻二醇通过戊糖-磷酸途径优化葡萄糖代谢。
Deficient bioenergetics and diminished redox conservation have been implicated in the development of cerebral ischemia/reperfusion injury. In this study, the mechanisms underlying the neuroprotective effects of cannabidiol (CBD), a nonpsychotropic compound derived from Cannabis sativa with FDA-approved antiepilepsy properties, were studied in vitro using an oxygen–glucose-deprivation/reperfusion (OGD/R) model in a mouse hippocampal neuronal cell line. CBD supplementation during reperfusion rescued OGD/R-induced cell death, attenuated intracellular ROS generation and lipid peroxidation, and simultaneously reversed the abnormal changes in antioxidant biomarkers. Using the Seahorse XFe24 Extracellular Flux Analyzer, we found that CBD significantly improved basal respiration, ATP-linked oxygen consumption rate, and the spare respiratory capacity, and augmented glucose consumption in OGD/R-injured neurons. The activation of glucose 6-phosphate dehydrogenase and the preservation of the NADPH/NADP+ ratio implies that the pentose-phosphate pathway is stimulated by CBD, thus protecting hippocampal neurons from OGD/R injury. This study is the first to document the neuroprotective effects of CBD against OGD/R insult, which depend in part on attenuating oxidative stress, enhancing mitochondrial bioenergetics, and modulating glucose metabolism via the pentose-phosphate pathway, thus preserving both energy and the redox balance. Cannabidiol protects hippocampal neurons from OGD/R-induced oxidative stress. Cannabidiol enhances mitochondrial bioenergetics. Cannabidiol optimizes glucose metabolism via the pentose-phosphate pathway.