摘要:
目的: 从中药祖师麻中发现有效的神经保护成分,阐明其治疗神经退行性疾病的药效物质基础。 方法: 使用体外培养的大鼠皮层神经元细胞作为筛选系统,综合运用各种色谱技术进行活性跟踪指导下的分离,对发现的活性成分在体外细胞水平研究其神经保护机制。 结果: 我们发现中药祖师麻的甲醇提取物可显著地减轻由谷氨酸(L-glutamate)、海人藻酸(kainic acid,KA)和过氧化氢(H2O2)诱导的大鼠皮层神经元细胞损伤。从祖师麻中分离纯化了一系列化合物,其中活性最强的是荛花酚(wikstromol)。荛花酚在50μM的浓度下可显著地降低H2O2诱导的细胞损伤。荛花酚显著地减少了细胞内谷胱甘肽、超氧化物歧化酶等抗氧化物质的下降,并减轻由兴奋性神经递质(谷氨酸、海人藻酸)诱导的神经毒性损伤,但不能减轻由N-甲基-D-天冬氨酸(NMDA)诱导的神经毒性损伤。 结论: 本研究确证了荛花酚可作为一种天然神经细胞保护剂,推测其神经保护机制可能是通过抗氧化作用实现的。
Abstract:
Objective To identify the material basis of the novel neuroprotective compounds from traditional chinese medicine Daphne giraldii in the treatment of neurodegenerative disorders.
Methonds Activity-guided fractionation of several chromatographic techniques were used for the isolation of the neuroprotective compounds.The cultured cortical neurons of rats were used as screening system. Results The methanolic extract from dried roots of Daphne giraldii significantly mitigated the neurotoxicity induced by L-glutamate,kainic acid and 2O2 in this screening system.The neuroprotective compound was identified as wikstromol.At a concentration of 50 μM,wikstromol significantly reduced neurotoxicity induced by 2O2.Wikstromol significantly reduced the decrease of glutathione,superoxide dismutase,and other enzymes that participate in the cellular defense against oxidative stress.Furthermore,wikstromol alleviated neurotoxicity induced by the excitotoxic neurotransmitter,L-glutamate and kainic acid,but not that mediated by N-methyl-D-aspartate. Conclusion Wikstromol was demonstrated to be efficacious in protecting neurons from oxidative stress.The neuroprotective mechanism of wikstromol may due to its antioxidant effect.