Fujimaki Takahiro, Saiki Shinji, Tashiro Etsu, Yamada Daisuke, Kitagawa Mitsuhiro, Hattori Nobutaka, Imoto Masaya
Department of Biosciences and Informatics, Faculty of Science and Technology, Keio University, Yokohama, Japan.
Department of Neurology, Juntendo University School of Medicine, Bunkyo, Tokyo.
PLoS One. 2014 Jun 24;9(6):e100395. doi: 10.1371/journal.pone.0100395. eCollection 2014.
In the course of screening for the anti-Parkinsonian drugs from a library of traditional herbal medicines, we found that the extracts of choi-joki-to and daio-kanzo-to protected cells from MPP+-induced cell death. Because choi-joki-to and daio-kanzo-to commonly contain the genus Glycyrrhiza, we isolated licopyranocoumarin (LPC) and glycyrurol (GCR) as potent neuroprotective principals from Glycyrrhiza. LPC and GCR markedly blocked MPP+-induced neuronal PC12D cell death and disappearance of mitochondrial membrane potential, which were mediated by JNK. LPC and GCR inhibited MPP+-induced JNK activation through the suppression of reactive oxygen species (ROS) generation, thereby inhibiting MPP+-induced neuronal PC12D cell death. These results indicated that LPC and GCR derived from choi-joki-to and daio-kanzo-to would be promising drug leads for PD treatment in the future.
在从传统草药库中筛选抗帕金森病药物的过程中,我们发现柴朴汤和大柴胡汤的提取物可保护细胞免受MPP⁺诱导的细胞死亡。由于柴朴汤和大柴胡汤通常都含有甘草属植物,我们从甘草中分离出了具有强大神经保护作用的licopyranocoumarin(LPC)和甘草次酸(GCR)。LPC和GCR显著阻断了MPP⁺诱导的神经元PC12D细胞死亡以及线粒体膜电位的消失,这是由JNK介导的。LPC和GCR通过抑制活性氧(ROS)的产生来抑制MPP⁺诱导的JNK激活,从而抑制MPP⁺诱导的神经元PC12D细胞死亡。这些结果表明,柴朴汤和大柴胡汤中的LPC和GCR有望成为未来治疗帕金森病的药物先导物。