Hwang Cheol Kyu, Chun Hong Sung
Department of Pharmacology, University of Minnesota Medical School, Minneapolis, MN 55455, USA.
Biosci Biotechnol Biochem. 2012;76(3):536-43. doi: 10.1271/bbb.110842.
Licorice (Glycyrrhiza uralensis) is a medicinal herb containing various bioactive components implicated in antioxidative, anti-inflammatory, antiviral, and neuroprotective effects, but the effects of licorice against Parkinson's disease (PD)-related dopaminergic cell death have not been studied. In this study, we investigated the protective effects of isoliquiritigenin (ISL) isolated from Glycyrrhiza uralensis on 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in a dopaminergic cell line, SN4741. ISL (1 µM) significantly attenuated 6-OHDA (50 µM)-induced reactive oxygen species (ROS) and nitric oxide (NO) generation and apoptotic cell death. ISL pretreatment effectively suppressed 6-OHDA-mediated upregulation of Bax, p-c-Jun N-terminal kinase (JNK), p-p38 mitogen-activated protein (MAP) kinase, cytochrome c release, and caspase 3 activation. In addition, ISL significantly attenuated 6-OHDA-induced Bcl-2, brain-derived neurotrophic factor (BDNF), and mitochondrial membrane potential (MMP) reduction. Pharmacological inhibitors of the phosphatidylinositol 3-kinase (PI3K)-Akt/protein kinase B (PKB) pathway reversed ISL-mediated neuroprotection against 6-OHDA toxicity in SN4741 cells. These results provide the first evidence that ISL can protect dopaminergic cells under oxidative stress conditions by regulating the apoptotic process.
甘草（Glycyrrhiza uralensis）是一种药用植物，含有多种具有抗氧化、抗炎、抗病毒和神经保护作用的生物活性成分，但甘草对帕金森病（PD）相关多巴胺能细胞死亡的影响尚未得到研究。在本研究中，我们研究了从甘草中分离出的异甘草素（ISL）对多巴胺能细胞系SN4741中6-羟基多巴胺（6-OHDA）诱导的神经毒性的保护作用。ISL（1 μM）显著减弱了6-OHDA（50 μM）诱导的活性氧（ROS）和一氧化氮（NO）生成以及凋亡细胞死亡。ISL预处理有效抑制了6-OHDA介导的Bax、磷酸化c-Jun氨基末端激酶（JNK）、磷酸化p38丝裂原活化蛋白（MAP）激酶上调、细胞色素c释放和半胱天冬酶3激活。此外，ISL显著减弱了6-OHDA诱导的Bcl-2、脑源性神经营养因子（BDNF）和线粒体膜电位（MMP）降低。磷脂酰肌醇3激酶（PI3K）-Akt/蛋白激酶B（PKB）途径的药理学抑制剂逆转了ISL介导的对SN4741细胞中6-OHDA毒性的神经保护作用。这些结果提供了首个证据，表明ISL可通过调节凋亡过程在氧化应激条件下保护多巴胺能细胞。
