Department of Neurophysiology, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan.
Tea Science Center, Graduate School of Integrated Pharmaceutical and Nutritional Sciences, University of Shizuoka, Shizuoka, Japan.
Mol Nutr Food Res. 2017 Dec;61(12). doi: 10.1002/mnfr.201700294. Epub 2017 Nov 3.
To understand the mechanism by which green tea lowers the risk of dementia, focus was placed on the metabolites of epigallocatechin gallate (EGCG), the most abundant catechin in green tea. Much of orally ingested EGCG is hydrolyzed to epigallocatechin (EGC) and gallic acid. In rats, EGC is then metabolized mainly to 5-(3',5'-dihydroxyphenyl)-γ-valerolactone (EGC-M5) and its conjugated forms, which are distributed to various tissues. Therefore, we examined the permeability of these metabolites into the blood-brain barrier (BBB) and nerve cell proliferation/differentiation in vitro.
The permeability of EGC-M5, glucuronide, and the sulfate of EGC-M5, pyrogallol, as well as its glucuronide into the BBB were examined using a BBB model kit. Each brain- and blood-side sample was subjected to liquid chromatography tandem-mass spectrometry analysis. BBB permeability (%, in 0.5 h) was 1.9-3.7%. In human neuroblastoma SH-SY5Y cells, neurite length was significantly prolonged by EGC-M5, and the number of neurites was increased significantly by all metabolites examined.
The permeability of EGC-M5 and its conjugated forms into the BBB suggests that they reached the brain parenchyma. In addition, the ability of EGC-M5 to affect nerve cell proliferation and neuritogenesis suggests that EGC-M5 may promote neurogenesis in the brain.
为了了解绿茶降低痴呆风险的机制，研究重点放在表没食子儿茶素没食子酸酯（EGCG）的代谢物上，EGCG 是绿茶中含量最丰富的儿茶素。口服摄入的 EGCG 很大一部分被水解为表儿茶素（EGC）和没食子酸。在大鼠中，EGC 主要代谢为 5-(3',5'-二羟基苯基）-γ-缬草酸（EGC-M5）及其共轭形式，分布到各种组织。因此，我们检查了这些代谢物进入血脑屏障（BBB）的通透性以及体外神经细胞增殖/分化的情况。
使用 BBB 模型试剂盒检查了 EGC-M5、葡萄糖醛酸苷、EGC-M5 的硫酸盐、焦儿茶酚及其葡萄糖醛酸苷进入 BBB 的通透性。每个脑侧和血侧样本均进行液相色谱串联质谱分析。BBB 通透性（0.5 小时内的百分比）为 1.9-3.7%。在人神经母细胞瘤 SH-SY5Y 细胞中，EGC-M5 显著延长了神经突长度，所有检查的代谢物都显著增加了神经突的数量。
EGC-M5 及其共轭形式进入 BBB 的通透性表明它们到达了脑实质。此外，EGC-M5 影响神经细胞增殖和神经突生成的能力表明，EGC-M5 可能促进大脑中的神经发生。
