Guangdong Institute for Drug Control, Guangzhou, China.
J Pharm Pharmacol. 2011 Sep;63(9):1169-74. doi: 10.1111/j.2042-7158.2011.01293.x. Epub 2011 Jun 21.
Previously, the flavonoid (±)-catechin was shown to exert potent neuroprotective action in the mouse 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinson's disease model. The purpose of this study was to investigate whether the different enantiomers of catechin ((+)-catechin, (-)-catechin and (±)-catechin, a 50:50 mixture of (+)-catechin and (-)-catechin) could protect SH-SY5Y cells against 1-methyl-4-phenylpyridinium ion (MPP(+) ) toxicity by decreasing the generation of oxygen free radicals. The inhibitive effect of (±)-catechin on JNK/c-Jun activation was investigated.
The effects of (+)-catechin, (-)-catechin or (±)-catechin in protecting against MPP(+) toxicity were evaluated and compared in SH-SY5Y cells by testing the release of lactate dehydrogenase. The generation of reactive oxygen species (ROS) was measured by immunochemistry and the phosphorylation level of JNK/c-Jun was determined by Western blotting.
In SH-SY5Y cells, (+)-catechin, (-)-catechin or (±)-catechin reduced apoptosis induced by MPP(+) and decreased ROS generation caused by MPP(+) . Different enantiomers of catechin showed protective effects at similar potency. Moreover (±)-catechin decreased JNK/c-Jun phosphorylation which was increased by MPP(+).
Catechin and its two enantiomers could protect SH-SY5Y cells against MPP(+) cytotoxicity at a similar potency. Antioxidative stress and inhibition of the JNK/c-Jun signalling pathway might have been involved in the neuroprotective mechanisms of catechin against MPP(+) cytotoxicity in SH-SY5Y cells.
先前的研究表明，黄酮类化合物（±）-儿茶素在小鼠 1-甲基-4-苯基-1,2,3,6-四氢吡啶诱导的帕金森病模型中具有强大的神经保护作用。本研究的目的是探讨儿茶素的不同对映异构体（(+)-儿茶素、(-)-儿茶素和（±）-儿茶素，（+）-儿茶素和（-）-儿茶素的 50:50 混合物）是否通过减少氧自由基的产生来保护 SH-SY5Y 细胞免受 1-甲基-4-苯基吡啶鎓离子（MPP(+)）毒性。研究了（±）-儿茶素对 JNK/c-Jun 激活的抑制作用。
通过检测乳酸脱氢酶的释放，评估并比较（+）-儿茶素、(-)-儿茶素或（±）-儿茶素在保护 SH-SY5Y 细胞免受 MPP(+)毒性中的作用。通过免疫化学法测定活性氧（ROS）的生成，用 Western blot 法测定 JNK/c-Jun 的磷酸化水平。
在 SH-SY5Y 细胞中，（+）-儿茶素、(-)-儿茶素或（±）-儿茶素均可减少 MPP(+)诱导的细胞凋亡，减少 MPP(+)引起的 ROS 生成。儿茶素的不同对映异构体表现出相似的保护作用。此外，（±）-儿茶素降低了 MPP(+)引起的 JNK/c-Jun 磷酸化。
儿茶素及其两种对映异构体对 MPP(+)细胞毒性具有相似的保护作用。抗氧化应激和抑制 JNK/c-Jun 信号通路可能参与了儿茶素对 SH-SY5Y 细胞 MPP(+)细胞毒性的神经保护机制。
