Parkinson's disease (PD) is a neurodegenerative disease characterized by tremor, rigidity, bradykinesia, and gait impairment. So far, very few pharmacological agents have been isolated or developed that effectively inhibit the progression of PD. However, several studies have demonstrated that Oxidative Stress play critical roles in PD. Schisandra chinensis (Turez.) Baill (S. chinensis) has long been used for thousands of years as a herbal drug under the name of Wuweizi in Traditional Chinses Medicine (TCM). Schisantherin A (SchiA) is a dibenzocyclooctadiene lignan isolated from the fruit of S. chinensis, has been shown to produce cardioprotective, liver-protective, anti-tumor and anti-oxidant activities. In an attempt to understand the neuroprotective effect of S. chinensis and to elucidate its underlying mechanism of action, the ethanolic extract of S. chinensis and SchiA was investigated using zebrafish and human dopaminergic SH-SY5Y cell models. In this study, the selective dopaminergic neurotoxin 6-hydroxydopamine (6-OHDA) was used to induce neural damage in SH-SY5Y cells and zebrafish models. Pretreatment with SchiA offered neuroprotection against 6-OHDA induced SH-SY5Y cell death. Moreover, SchiA could prevent 6-OHDA induced SH-SY5Y cell apoptosis and 6-OHDA-stimulated dopaminergic neuron loss in zebrafish. A mechanistic study showed that SchiA could inhibit NO over-production and iNOS over-expression in SH-SY5Y cells. Results showed that SchiA suppressed 6-OHDA induced reactive oxygen species generation, cellular injury and apoptotic cell death. SchiA also protects against the 6-OHDA induced SH-SY5Y cell death mediated by regulation of AKT/GSK3β expression. These findings demonstrate that SchiA may have potential therapeutic value for neurodegenerative disease associated with oxidative stress such as PD. Key words Neurodegenerative disease, Parkinson's disease, Schisantherin A, ROS, 6-OHDA, , NO, AKT/GSK3β, SH-SY5Y, Zebrafish

探討傳統中藥五味子的醇提物以及主要有效成份五味子酯甲在帕金森病實驗模型上的神經保護作用及其機制。 帕金森病作為世界第二大神經退行性疾病，近年來蔓延迅速。目前的治療手段以缓解症狀為主，並無有效防治藥物。五味子是具有悠久用藥歷史的傳統藥物之一。木脂素類化合物是五味子的主要有效成份。我們發現五味子醇提物及五味子酯甲在帕金森病實驗模型生表現出良好的神經保護效果。在6-羥基多巴胺誘導的SH-SY5Y細胞損傷模型上，五味子醇提物及五味子酯甲均表現出良好的保護作用。首先，五味子醇提物及五味子酯甲都可以有效地抑制6-羥基多巴胺誘導的活性氧自由基的生成。進一步機理研究顯示五味子酯甲在SH-SY5Y細胞上通過上調 細胞生存相關的PI3K/AKT和MAPK信號傳導通路以区下調細胞凋亡先關的蛋白表達，阻断炎症相關的iNOS通路來實現保護效果。同時，在6-羥基多巴胺誘導的斑馬魚多巴胺能神經元損傷模型中，五味子酯甲同樣表現出良好的保護效果。五味子酯甲滅少了六羥基多巴胺誘導的斑馬魚多巴胺神經元丢失， 這為五味子酯甲的神經保護作用作了進一步的印證。 綜上，五味子酯甲可能成為一個有潛力的多靶點抗帕金森藥物。 關鍵字:五味子;神經保護;神經退行性病;帕金森症;SH-SY5Y细胞;斑馬魚;6-羥基多巴胺;一氧化氮;誘導型一氧化氮合酶;AKT/GSK3β;自由基;凋亡.