Pervin Monira, Unno Keiko, Nakagawa Aimi, Takahashi Yuu, Iguchi Kazuaki, Yamamoto Hiroyuki, Hoshino Minoru, Hara Aya, Takagaki Akiko, Nanjo Fumio, Minami Akira, Imai Shinjiro, Nakamura Yoriyuki
Tea Science Center, Graduate School of Integrated Pharmaceutical and Nutritional Sciences, University of Shizuoka, Shizuoka 422-8526, Japan.
Department of Neurophysiology, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka 422-8526, Japan.
Biochem Biophys Rep. 2017 Jan 5;9:180-186. doi: 10.1016/j.bbrep.2016.12.012. eCollection 2017 Mar.
The consumption of green tea catechins (GTCs) suppresses age-related cognitive dysfunction in mice. GTCs are composed of several catechins, of which epigallocatechin gallate (EGCG) is the most abundant, followed by epigallocatechin (EGC). Orally ingested EGCG is hydrolyzed by intestinal biota to EGC and gallic acid (GA). To understand the mechanism of action of GTCs on the brain, their permeability of the blood brain barrier (BBB) as well as their effects on cognitive function in mice and on nerve cell proliferation were examined.
The BBB permeability of EGCG, EGC and GA was examined using a BBB model kit. SAMP10, a mouse model of brain senescence, was used to test cognitive function . Human neuroblastoma SH-SY5Y cells were used to test nerve cell proliferation and differentiation.
The BBB permeability (%, in 30 min) of EGCG, EGC and GA was 2.8±0.1, 3.4±0.3 and 6.5±0.6, respectively. The permeability of EGCG into the BBB indicates that EGCG reached the brain parenchyma even at a very low concentration. The learning ability of SAMP10 mice that ingested EGCG (20 mg/kg) was significantly higher than of mice that ingested EGC or GA. However, combined ingestion of EGC and GA showed a significant improvement comparable to EGCG. SH-SY5Y cell growth was significantly enhanced by 0.05 µM EGCG, but this effect was reduced at higher concentrations. The effect of EGC and GA was lower than that of EGCG at 0.05 µM. Co-administration of EGC and GA increased neurite length more than EGC or GA alone.
Cognitive dysfunction in mice is suppressed after ingesting GTCs when a low concentration of EGCG is incorporated into the brain parenchyma via the BBB. Nerve cell proliferation/differentiation was enhanced by a low concentration of EGCG. Furthermore, the additive effect of EGC and GA suggests that EGCG sustains a preventive effect after the hydrolysis to EGC and GA.
食用绿茶儿茶素（GTCs）可抑制小鼠与年龄相关的认知功能障碍。GTCs由多种儿茶素组成，其中表没食子儿茶素没食子酸酯（EGCG）含量最高，其次是表没食子儿茶素（EGC）。口服的EGCG会被肠道微生物群水解为EGC和没食子酸（GA）。为了解GTCs对大脑的作用机制，研究了它们的血脑屏障（BBB）通透性以及对小鼠认知功能和神经细胞增殖的影响。
使用血脑屏障模型试剂盒检测EGCG、EGC和GA的血脑屏障通透性。采用脑衰老小鼠模型SAMP10来测试认知功能。用人神经母细胞瘤SH-SY5Y细胞来测试神经细胞增殖和分化。
EGCG、EGC和GA的血脑屏障通透性（30分钟内的百分比）分别为2.8±0.1、3.4±0.3和6.5±0.6。EGCG进入血脑屏障的通透性表明，即使在极低浓度下，EGCG也能到达脑实质。摄入EGCG（20毫克/千克）的SAMP10小鼠的学习能力显著高于摄入EGC或GA的小鼠。然而，联合摄入EGC和GA显示出与EGCG相当的显著改善。0.05微摩尔的EGCG显著促进了SH-SY5Y细胞的生长，但在较高浓度下这种作用减弱。在0.05微摩尔时，EGC和GA的作用低于EGCG。联合给予EGC和GA比单独给予EGC或GA更能增加神经突长度。
当低浓度的EGCG通过血脑屏障进入脑实质后，摄入GTCs可抑制小鼠的认知功能障碍。低浓度的EGCG可增强神经细胞增殖/分化。此外，EGC和GA的相加作用表明，EGCG水解为EGC和GA后仍具有预防作用。
