Lee Yujeong, Chun Hye Jeong, Lee Kyung Moon, Jung Young-Suk, Lee Jaewon
Department of Pharmacy, College of Pharmacy, Molecular Inflammation Research Center for Aging Intervention, Pusan National University, Busan 609-735, Republic of Korea.
Department of Pharmacy, College of Pharmacy, Molecular Inflammation Research Center for Aging Intervention, Pusan National University, Busan 609-735, Republic of Korea.
Brain Res. 2015 Nov 19;1627:233-42. doi: 10.1016/j.brainres.2015.09.029. Epub 2015 Oct 3.
Parkinson's disease (PD) is the second-most common neurodegenerative disease after Alzheimer's disease, and is characterized by dopaminergic neuronal loss in midbrain. The MPTP-induced PD model has been well characterized by motor deficits and selective dopaminergic neuronal death accompanied by glial activation. Silibinin is a constituent of silymarin, an extract of milk thistle seeds, and has been proposed to have hepatoprotective, anti-cancer, anti-oxidative, and neuroprotective effects. In the present study, the authors studied the neuroprotective effects of silibinin in an acute MPTP model of PD. Silibinin was administered for 2 weeks, and then MPTP was administered to mice over 1 day (acute MPTP induced PD). Silibinin pretreatment effectively ameliorated motor dysfunction, dopaminergic neuronal loss, and glial activations caused by MPTP. In addition, an in vitro study demonstrated that silibinin suppressed astroglial activation and ERK and JNK phosphorylation in primary astrocytes in response to MPP(+) treatment. These findings show silibinin protected dopaminergic neurons in an acute MPTP-induced mouse model of PD, and suggest its neuroprotective effects might be mediated by the suppression of astrocyte activation via the inhibition of ERK and JNK phosphorylation. In conclusion, the study indicates silibinin should be viewed as a potential treatment for PD and other neurodegenerative diseases associated with neuroinflammation.
帕金森病（PD）是仅次于阿尔茨海默病的第二常见神经退行性疾病，其特征是中脑多巴胺能神经元丢失。MPTP诱导的PD模型已通过运动缺陷、选择性多巴胺能神经元死亡以及伴随的胶质细胞激活得到了充分表征。水飞蓟宾是水飞蓟素的一种成分，水飞蓟素是水飞蓟种子的提取物，有人提出它具有肝脏保护、抗癌、抗氧化和神经保护作用。在本研究中，作者研究了水飞蓟宾在急性MPTP诱导的PD模型中的神经保护作用。水飞蓟宾给药2周，然后在1天内给小鼠注射MPTP（急性MPTP诱导的PD）。水飞蓟宾预处理有效改善了MPTP引起的运动功能障碍、多巴胺能神经元丢失和胶质细胞激活。此外，一项体外研究表明，水飞蓟宾抑制了原代星形胶质细胞对MPP(+)处理的星形胶质细胞激活以及ERK和JNK磷酸化。这些发现表明水飞蓟宾在急性MPTP诱导的PD小鼠模型中保护了多巴胺能神经元，并表明其神经保护作用可能是通过抑制ERK和JNK磷酸化来抑制星形胶质细胞激活介导的。总之，该研究表明水飞蓟宾应被视为PD和其他与神经炎症相关的神经退行性疾病的潜在治疗方法。
