Sakai Risa, Irie Yoshifumi, Murata Takeshi, Ishige Atsushi, Anjiki Naoko, Watanabe Kenji
Department of Oriental Medicine, Keio University School of Medicine, Japan.
Phytother Res. 2007 Sep;21(9):868-73. doi: 10.1002/ptr.2172.
Parkinson's disease (PD) is a neurodegenerative disease of the brain characterized by the progressive loss of dopaminergic neurons in the substantia nigra (SN). No clinically proven drugs that may halt or retard the progression of PD have been reported. This study examined the anti-PD effect of a traditional Japanese/Chinese herbal remedy Toki-to (TKT) using mice treated with a neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydroxypyridine (MPTP). TKT showed improvement of MPTP-induced PD-like symptoms (bradykinesia) in a behavioral test (pole test). Histological studies of SNs from these mice demonstrated that TKT had a protective effect on dopaminergic neurons against MPTP neurotoxicity. Real-time RT-PCR analyses of mRNA from SNs demonstrated that expression of tyrosine hydroxylase (TH) and dopamine transporter (DAT) genes were decreased by MPTP treatment and that these decreases were reversed by TKT administration prior to MPTP treatment. DNA microarray analyses indicated that TKT per se suppressed gene expression of serum- and glucocorticoid regulated kinase (SGK) that is believed to be a molecule that drives the pathogenesis of PD. Hence, it is suggested that TKT may inhibit the activation of SGK at the transcriptional level and thusmay participate in halting the progression of MPTP-induced neurotoxicity.
帕金森病（PD）是一种脑部神经退行性疾病，其特征是黑质（SN）中多巴胺能神经元逐渐丧失。目前尚无临床证实的可阻止或延缓帕金森病进展的药物报道。本研究使用经神经毒素1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）处理的小鼠，检测了传统日本/中国草药方剂 toki-to（TKT）的抗帕金森病作用。在行为测试（杆试验）中，TKT显示出对MPTP诱导的帕金森病样症状（运动迟缓）有改善作用。对这些小鼠黑质的组织学研究表明，TKT对多巴胺能神经元具有保护作用，可抵抗MPTP的神经毒性。对黑质mRNA进行的实时RT-PCR分析表明，MPTP处理可使酪氨酸羟化酶（TH）和多巴胺转运体（DAT）基因的表达降低，而在MPTP处理前给予TKT可逆转这些降低。DNA微阵列分析表明，TKT本身可抑制血清和糖皮质激素调节激酶（SGK）的基因表达，而SGK被认为是驱动帕金森病发病机制的一种分子。因此，提示TKT可能在转录水平抑制SGK的激活，从而可能参与阻止MPTP诱导的神经毒性进展。
