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Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/23500
標題: 以PC12細胞為模式開發抗阿滋海默症的中草藥
Development of herbal medicines for the treatment of Alzheimer's disease: PC12 cells as a model
作者: 游裕瑩
Yu, Yu-Ying
關鍵字: PC12 cells;PC12細胞;herbal medicines;阿滋海默症;中草藥
出版社: 生命科學院碩士在職專班
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摘要: 
阿滋海默症 (Alzheimer’s disease, AD) 是一種漸進式的神經退化性疾病。目前，在科學上對於阿滋海默症的分子醫學層面之致病機轉已漸明朗化，主流假說認為是由於β類澱粉前驅蛋白質 (β-amyloid precursor protein; APP) 降解所致之β-類澱粉胜肽 (β-amyloid pepide; Aβ) 與人類脂蛋白元E4 (apolipoprotein E4; apoE4) 糾結沉積，啟動腦部神經細胞氧化損傷與發炎反應而開始。在阿滋海默症患者的大腦內部可以觀察到神經纖維糾結 (neurofibrillary tangles; NFT) 及類澱粉斑塊 (amyloid plaques)。本研究選擇源自大鼠腎上腺髓質嗜鉻細胞瘤之PC12細胞，採用未分化的PC12細胞 (nPC12 cells) 和以神經生長因子 (nerve growth factor; NGF) 處理促使其分化的PC12細胞 (dPC12 cells) 為細胞模式，探討可促進nPC12細胞增生或分化，或配合個別或共同經Aβ∕apoE4糾結物處理，導致細胞氧化性損傷進而致細胞凋亡的細胞模式，篩選有防治阿滋海默症之中草藥，探討對象乃由具有中醫藥理論為基礎的科學中藥中挑出，並以銀杏萃出物 (EGb 761) 或神經生長因子作為正對照組。
結果顯示熟地黃、枳實、茯苓、人參之水萃物和杜仲之乙醇萃物，有促進nPC12細胞長出突觸的潛力顯示可促進分化；石菖蒲、茯苓、巴戟天、五味子、人參、刺五加、當歸之水萃物，或還少丹、熟地黃之乙醇萃物有促進細胞增生的活性；在模擬阿滋海默症患者腦內的神經細胞趨阿滋海默症的環境實驗，還少丹水萃物和乙醇萃物及石菖蒲乙醇萃物具有保護dPC12細胞面對Aβ/apoE4所造成的氧化性損傷。本研究並以高效液相層析法分析了上述活性分劃之成分譜，此結果有助於未來進而探討其中的活性成分。或以複方的形式開發出抗阿滋海默症的新組合 (複方藥物)。本研究藉阿滋海默症分子病因為基礎開發中草藥有效成分，未來有助於發展新穎中草藥。

Alzheimer's disease (AD) is a progressive neurodegenerative disease in humans. Recent advances in the molecular medicine on this disease have greatly revealed the underlying mechanisms. The recent working hypothesis, namely β-amyloid (Aβ) hypothesis, suggests that erroneous processing of amyloid precursor protein (APP) by β- and γ-secretases produces Aβ and aggregation of Aβ or co-aggregation of Aβ with apolipoprotein E (apoE) triggers disease progression. The depositions of neurofibrillary tangles (NFT) and amyloid plaques are the hallmarks of AD pathology. In this study, naïve PC12 (nPC12) cells and nerve growth factor (NGF)-treated, differentiated PC12 (dPC12) cells were used as a cellular model to search for potential herbal medicines that may promote cell proliferation or differentiation. dPC12 cells were also treated with Aβ/apoE co-aggregates to mimic AD-induced neuronal damage and apoptosis. This model was used to search for bioactive fractions or components that may prevent or inhibit neuronal death in AD. Herbal medicines, reported in traditional Chinese medicine with implications or evidence in modern pharmacologic studies, were chosen for this purpose. EGb761, originated from Gingko biloba, and NGF were used as positive controls.
Results showed that the aqueous extracts of Rehmannia glutinosa, Citrus aurantium, Poria cocos, and Panax ginseng or the ethanolic extracts of Eucommia ulmoides promoted the nPC12 cell neurite out-growth, a marker of differentiation. The aqueous extracts of Acorus tatrinowii, Poria cocos, Morida officinalis, Schisandra chinensis, Panax ginserg, Acanthopanax senticosus, and Angelica sinensis or the ethanolic extracts of Huan Shao Tan and Rehmannia glutinosa promoted nPC12 cell proliferation. In the model that simulates AD progression (treatment with Aβ/ApoE4 aggregates), the aqueous and ethanolic extracts of Huan Shao Tan, and the ethanolic extracts of Acorus tatrinowii protected against Aβ-apoE4-induced cell damages. High-performance liquid chromatography (HPLC) was used to characterize the chemical profiles of bioactive fractions, which may help in future identification of bioactive compounds. In conclusion, this study provides valuable information that may shed light on future development of molecular pathogenesis-based novel herbal medicines for the treatment of AD.
URI: http://hdl.handle.net/11455/23500
其他識別: U0005-1908201016270200
Appears in Collections:生命科學系所

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