Tian Yuan-Yuan, Jiang Bo, An Li-Jia, Bao Yong-Ming
Department of Environmental And Biological Science And Technology, Dalian University of Technology, Dalian, Liaoning, 116024, China.
Eur J Pharmacol. 2007 Jul 30;568(1-3):142-8. doi: 10.1016/j.ejphar.2007.04.039. Epub 2007 Apr 30.
The neuroprotective effects of catalpol, an iridoid glycoside present in the roots of Rehmannia glutinosa, on 1-methyl-4-phenylpyridinium (MPP(+))-induced oxidative stress in cultured mesencephalic neurons, especially dopaminergic neurons, were investigated. Exposure of mesencephalic neurons to 10microM MPP(+) induced a leakage of lactate dehydrogenase (LDH) and decreased cell viability, measured with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Catalpol increased neuron viability and markedly attenuated MPP(+)-induced dopaminergic neuron death in a dose-dependent manner. In order to clarify the neuroprotective mechanism of catalpol, mitochondrial function, the activities of endogenous antioxidants and the lipid peroxide content were measured. The results indicated that catalpol prevented the MPP(+)-induced inhibition of complex I activity and the loss of mitochondrial membrane potential. In addition, catalpol reduced the content of lipid peroxide and increased the activity of glutathione peroxidase and superoxide dismutase. Taken together, the above results suggest that catalpol may be a candidate drug for the treatment of oxidative stress-induced neurodegenerative disease.
梓醇是地黄根中存在的一种环烯醚萜苷，本研究探讨了其对1-甲基-4-苯基吡啶离子（MPP(+)）诱导的中脑神经元尤其是多巴胺能神经元氧化应激的神经保护作用。中脑神经元暴露于10μM MPP(+)会导致乳酸脱氢酶（LDH）泄漏，并降低细胞活力，通过3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐（MTT）法进行测定。梓醇以剂量依赖性方式提高神经元活力，并显著减轻MPP(+)诱导的多巴胺能神经元死亡。为了阐明梓醇的神经保护机制，对线粒体功能、内源性抗氧化剂活性和脂质过氧化物含量进行了测定。结果表明，梓醇可防止MPP(+)诱导的复合体I活性抑制和线粒体膜电位丧失。此外，梓醇降低了脂质过氧化物含量，并提高了谷胱甘肽过氧化物酶和超氧化物歧化酶的活性。综上所述，上述结果表明梓醇可能是治疗氧化应激诱导的神经退行性疾病的候选药物。
