Protective Effects of 28-O-Caffeoyl Betulin (B-CA) on the Cerebral Cortex of Ischemic Rats Revealed by a NMR-Based Metabolomics Analysis
Protective Effects of 28-O-Caffeoyl Betulin (B-CA) on the Cerebral Cortex of Ischemic Rats Revealed by a NMR-Based Metabolomics Analysis
复制标题
基于 NMR 的代谢组学分析揭示 28-O-咖啡酰桦木醇 (B-CA) 对缺血大鼠大脑皮层的保护作用
DOI：
10.1007/s11064-020-03202-z
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发表时间：
2021-01-03
影响因子：
4.4
通讯作者：
Zhang, Nai-xia
中科院分区：
文献类型：
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作者：
Liu, Xia;Ruan, Zhi;Zhang, Nai-xia
28-O-咖啡酰倍他林(B-CA)已被证实能缩小大脑中动脉闭塞(MCAO)所致的脑梗塞体积。B-CA是一种新的天然咖啡酰三萜的衍生物，与其药理作用靶点相关的信息很少(S)。到目前为止，还没有关于B-CA对大脑代谢影响的数据。本研究采用~1H-核磁共振代谢组学方法，研究了B-CA对大鼠大脑中动脉闭塞后脑代谢的影响。比较假手术组、MCAO + 载体组、MCAO + B-CA组在脑缺血后急性期(9h)大脑皮层的整体代谢变化。MCAO可引起缺血大鼠同侧皮质的多种改变，从而导致以NAA下调为特征的神经元损伤，包括能量代谢障碍、氧化应激和神经递质代谢。B-CA对MCAO大鼠脑缺血皮质有明显的抢救作用。具体地说，B-CA治疗改善了与缺血性中风进展相关的能量代谢功能障碍(反向调节琥珀酸、乳酸、支链氨基酸和肉碱的水平)、氧化应激(上调谷胱甘肽的水平)和神经递质代谢紊乱(反向调节γ-氨基丁酸和乙酰胆碱的水平)。给予B-CA后，3种磷脂相关代谢产物(O-磷胆碱、O-磷乙醇胺、sn-甘油-3-磷胆碱)和NAA水平显著提高。总体而言，我们的发现表明，B-CA治疗可能通过增强在大鼠大脑中动脉闭塞后观察到的大脑皮层代谢变化来提供神经保护。
28-O-caffeoyl betulin (B-CA) has been demonstrated to reduce the cerebral infarct volume caused by transient middle cerebral artery occlusion (MCAO) injury. B-CA is a novel derivative of naturally occurring caffeoyl triterpene with little information associated with its pharmacological target(s). To date no data is available regarding the effect of B-CA on brain metabolism. In the present study, a1H-NMR-based metabolomics approach was applied to investigate the therapeutic effects of B-CA on brain metabolism following MCAO in rats. Global metabolic profiles of the cortex in acute period (9 h after focal ischemia onset) after MCAO were compared between the groups (sham; MCAO + vehicle; MCAO + B-CA). MCAO induced several changes in the ipsilateral cortex of ischemic rats, which consequently led to the neuronal damage featured with the downregulation of NAA, including energy metabolism dysfunctions, oxidative stress, and neurotransmitter metabolism. Treatment with B-CA showed statistically significant rescue effects on the ischemic cortex of MCAO rats. Specifically, treatment with B-CA ameliorated the energy metabolism dysfunctions (back-regulating the levels of succinate, lactate, BCAAs, and carnitine), oxidative stress (upregulating the level of glutathione), and neurotransmitter metabolism disturbances (back-regulating the levels of γ-aminobutyric acid and acetylcholine) associated with the progression of ischemic stroke. With the administration of B-CA, the levels of three phospholipid related metabolites (O-phosphocholine,O-phosphoethanolamine, sn-glycero-3-phosphocholine) and NAA improved significantly. Overall, our findings suggest that treatment with B-CA may provide neuroprotection by augmenting the metabolic changes observed in the cortex following MCAO in rats.