Inhibition of Glycogen Synthase Kinase-3β by Falcarindiol Isolated from Japanese Parsley (Oenanthe javanica)
Inhibition of Glycogen Synthase Kinase-3β by Falcarindiol Isolated from Japanese Parsley (Oenanthe javanica)
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DOI：
10.1021/jf401042m
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发表时间：
2013-08-07
影响因子：
6.1
通讯作者：
Kimura, Ken-ichi
中科院分区：
文献类型：
--
作者：
Yoshida, Jun;Seino, Hiroko;Kimura, Ken-ichi
利用酵母YNS17突变株（zds1 Delta erg3 Delta pdr1 Delta pdr3 Delta）从日本欧芹（Oenanthe javanica）中分离得到一种具有抑制糖原合成酶激酶-3 β (GSK-3 β)活性的新生物活性。Falcarindiol以ATP非竞争性方式抑制GSK-3 β，使用人酶和发光激酶检测平台，K-i值为86.9 mu M。在10 μ m的剂量下，镰镰碱醇还能抑制大鼠肝癌H4IIE细胞中葡萄糖-6-磷酸酶（G6Pase）的基因表达，并保护小鼠神经母细胞瘤HT22细胞免受谷氨酸诱导的氧化性细胞死亡。在口服葡萄糖耐量试验（OGTT）中，口服含镰镰碱醇提取物（15 mg/kg）的大鼠血糖水平显著降低。这些发现表明，日本香菜可能是一种有效的食物成分，可以预防2型糖尿病和阿尔茨海默病。
A new biological activity of falcarindiol isolated from Japanese parsley (Oenanthe javanica) using the mutant yeast YNS17 strain (zds1 Delta erg3 Delta pdr1 Delta pdr3 Delta) was discovered as an inhibitor of glycogen synthase kinase-3 beta (GSK-3 beta). Falcarindiol inhibited GSK-3 beta in an ATP noncompetitive manner with a K-i value of 86.9 mu M using a human enzyme and luminescent kinase assay platform. Falcarindiol also both suppressed gene expression of glucose-6-phosphatase (G6Pase) in rat hepatoma H4IIE cells and protected mouse neuroblastoma HT22 cells from glutamate-induced oxidative cell death at 10 mu M. During an oral glucose tolerance test (OGTT), the blood glucose level was significantly decreased in the rats treated with oral administration of O. javanica extract containing falcarindiol (15 mg/kg). These findings indicate that Japanese parsley could be a useful food ingredient against type-2 diabetes and Alzheimer's disease.