台灣香檬萃取物在阿茲海默症模型細胞中之活性分析

Taipei Medical University Institutional Repository > 醫學科技學院 > 醫學檢驗暨生物技術學系所 > 博碩士論文 > Item 987654321/61844

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題名:	台灣香檬萃取物在阿茲海默症模型細胞中之活性分析 The activity analyses of Citrus depressa extracts in Alzheimer’s disease model cells.
作者:	林修民 LIN, HSIU-MIN
貢獻者:	醫學檢驗暨生物技術學系碩士班林詠峯
關鍵詞:	阿茲海默症;乙型類澱粉蛋白;澱粉樣前體蛋白;濤蛋白;台灣香檬 Alzheimer’s disease;Amyloid-β;Amyloid precursor protein;Citrus depressa;Tau
日期:	2022-01-12
上傳時間:	2022-08-12 11:44:35 (UTC+8)
摘要:	目的:阿茲海默症(Alzheimer’s disease, AD)為失智症中最常見的類別，是一種進行性退化神經疾病。目前已批准用於 AD 的治療藥物包括了膽鹼酯酶抑制劑(Cholinesterase inhibitors)以及 N-甲基-D-天門冬胺酸(N-methyl d-aspartate, NMDA)受體拮抗劑，它們對減緩 AD 症狀方面的治療是有效的，但無法治癒或預防該疾病，致使我們迫切的需要新的藥物能達到治癒或預防的功效。在此研究中我們探討台灣原生種香檬(Citrus depressa)萃取物對 AD 是否以及如何產生療效。方法:此研究中我們探討來自台灣香檬的三種萃取物(全果萃物、乾皮萃物、陳皮萃物)在AD 細胞模型的療效。AD 細胞株以神經母細胞瘤(Neuro-2a, N2a)經轉染突變的澱粉樣前體蛋白(amyloid precursor protein, APP) (APP-Swe/Ind)後建立而成。我們分析細胞存活率並以免疫細胞化學染色法觀測細胞型態及其經處理後的變化；以西方墨點法來觀察 APP蛋白的切割和 Tau 蛋白的磷酸化，以及細胞信息途徑的活化等情況。結果:實驗結果顯示，台灣香檬的三種萃取物皆明顯提升 AD 細胞活性並維持正常型態表現，三種萃取物之 IC50於 N2a 細胞中共同的濃度範圍約落於 300 μg/ml；經評估後，我們使用 100 μg/ml 為三種萃取物於轉染的 AD 模型細胞之共同安全濃度；處理後觀察到AD 細胞的神經纖維生長有明顯改善；分析 AD 細胞裂解物後發現 APP 異常修剪產物減少，並降低了 Tau 的磷酸化程度；且觀測到兩種活性路徑 ERK 及 Akt 的活化。相同濃度下，萃取物改善 APP 病理切割情形及 Tau 過度磷酸化情形以陳皮萃物最佳；ERK 路徑之活化以乾皮萃物最佳；Akt 路徑之活化以全果萃物最佳。結論:台灣香檬的萃取物可以抑制 APP 的異常修剪情況和 Tau 過度磷酸化，激活 ERK 和Akt 等路徑，以恢復 AD 細胞的生理狀態。總結而言，台灣香檬的萃取物為具潛力的 AD治療藥物。 Objective: Alzheimer’s disease (AD) is the most common type of dementia. The currently approved treatments for AD can only relieve symptoms but cannot effectively cure or prevent.Therefore, we urgently need specific drugs that can cure or prevent the disease. In this study, we explored whether and how the extracts of Citrus depressa, a native species of Taiwan, has a curative effect on AD. Methods: The three extracts of Citrus depressa (Crude extract, Dried peel extract, Fermented peel extract) were used in this study. The AD cell line was established from Neuro-2a cell (N2a) transfected with mutant amyloid precursor protein (APP) (APP-Swe/Ind). We analyzed cell viability and observed the cell differentiation by Immunocytochemistry. We used Western blotting to examine APP processing, Tau phosphorylation and the activation of cell signaling pathways. Results: The IC50 of the three extracts in N2a cells is within a common concentration of 300 μg/ml. After evaluation, we used 100 μg/ml as the common safe concentration of the three extracts in the transfected AD model cells. After treatment, AD cells were significantly improved in the neurite outgrowth; the pathological cleavage of APP and Tau phosphorylation were reduced;ERK and Akt pathways were activated. At the same concentration, fermented peel extract showed the best effect on inhibiting APP pathological cleavage and Tau phosphorylation; dried peel extract was the best on activating ERK pathway; crude extract was the best on activating Akt pathway. Conclusion: Citrus depressa extracts reduce Tau phosphorylation and APP processing, activating the ERK and Akt pathways to recover the AD cell physiology Citrus depressa extracts are potential candidates for AD treatment.
描述:	碩士指導教授:林詠峯委員:高淑慧委員:李慶國委員:林詠峯
資料類型:	thesis
顯示於類別:	[醫學檢驗暨生物技術學系所] 博碩士論文

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