臺灣博碩士論文加值系統

山胡椒 (Litsea cubeba Persoon)為台灣原住民傳統的調味料，有研究指出其果實精油及甲醇萃取物具有抗氧化、鎮靜止痛及改善焦慮與憂鬱等中樞神經系統失調的功能。老年失智症 (Senile dementia)為隨年齡增長及體內過度氧化損傷造成之神經退化性疾病，其中阿茲海默症 (Alzheimer’s disease, AD)為盛行率最高的一種，經由類澱粉蛋白 (Amyloid β protein, Aβ)斑塊沉積與tau蛋白過度磷酸化 (Phosphorylated tau protein, p-tau)造成神經纖維糾結於海馬迴組織中，導致記憶學習能力喪失及認知功能障礙。故本研究分析山胡椒果實精油之香氣組成，並以其粉末餵食類阿茲海默症小鼠，評估其記憶及學習能力改善之成效。結果顯示山胡椒因生長環境海拔越高、緯度越低及果實顏色越青，其精油含量越少。再以氣相層析質譜儀 (Gas chromatography–mass spectrometry, GC/MS)鑑定山胡椒果實精油主要由萜類化合物所組成，南投地區精油之檸檬烯、橙花醛及香葉醛等總量高於高雄地區且其精油之檸檬及柑橘香氣較為濃厚，並將各地區精油組成進行主成分分析 (Principal components analysis, PCA)，結果顯示山胡椒之生長緯度及海拔相似，其精油組成相近且位於第一及第二主成分間之主成分分數散點圖上同一區域。動物試驗結果顯示，經由類澱粉蛋白誘導手術及餵食山胡椒果實粉末及褪黑激素不會造成小鼠體重有急遽變化；於肝腎功能指數及切片判讀也未發現有發炎、空泡化及細胞壞死等病徵;另外，餵食山胡椒果實粉末相較於Aβ組雖然無法降低蛋白質羰基氧化物 (Protein carbonyl)濃度，但能顯著降低腦中丙二醛 (Malondialdehyde)及磷酸化τ-蛋白 (Phosphorylated τ-protein)等相關病徵氧化物含量及Aβ斑塊沉積量，藉以改善小鼠之記憶學習能力。綜合上述結果，山胡椒果實粉末可防止因類澱粉蛋白誘導所導致的氧化壓力上升以改善記憶及學習能力之障礙。

Litsea cubeba Persoon is a traditional seasoning used by Taiwanese aborigines. There are some studies indicating that Litsea cubeba fruits essential oil and its methanol extract have functions in antioxidation, sedation, analgesic and improvement of the central nervous system disorders such as anxiety and depression. Senile dementia is a neurodegenerative disease caused by aging and excessive oxidative damage in body and Alzheimer's disease (AD) has highest prevalence rate which caused by Amyloid β protein (Aβ plaques accumulation and hyperphosphorylated tau protein (p-tau) to form neurofibrillary tangles (NFTS) deposit in hippocampus that induces memory loss and cognitive impairment. Thus, the major aim of the study is to evaluate the volatile compounds of Litsea Cubeba fruit essential oils then ameliorate effect of Litsea Cubeba fruit powder (LCP) on memory and learning ability improvement in Aβ-induced alzheimer's mice. The results show that litsea cubeba fruits growing in high altitude, low latitude and fruit with greener color have lower essential oil content compared to others condition. Besides, the GC / MS analyses give the result that the essential oils are mainly composed of terpenoids. The total contents of limonene, neral and geranial in essential oil from Nantou areas are richer than Kaohsiung areas that cause the lemon and citrus smell are much stronger in Natou area’s essential oils. Using principal components analysis (PCA) to distinguish the composition of Litsea cubeba fruit essential oils from different areas, and the composition of essential oils growing in same area is similar to the one locating in the same region on score scatter plot of the first and the second principal components. The results of Aβ induced Alzheimer’s mice model show that Aβ-induced surgery model and mice fed with LCP and melatonin would not cause the mouse weight change sharply, the serum biochemical and histopathological alterations of liver and kidney were not found inflammation, vacuolization, and necrosis-related lesions. Moreover, compared with Aβ group, although fed LCP cannot decrease the concentration of protein carbonyl, it could significantly decrease the amount of malondialdehyde, phosphorylated τ-protein and deposition of Aβ plaques in brain then effectively improve the memory and learning ability impairment,
In summary, Litsea cubeba Persoon fruit has potential to be functional food to prevent the increase of oxidative stress induced by Aβthen ameliorates memory and learning ability.

摘要 i
Abstract iii
目錄 v
表次 viii
圖次 ix
縮寫表 xi
第一章 前言 1
第二章 文獻回顧 2
一、老化與失智 (Aging & dementia) 2
二、阿茲海默症 (Alzheimer’s disease) 4
(一) 阿茲海默症之發現與症狀 4
(二) 阿茲海默症之成因 5
(三) 阿茲海默症之診斷 12
(四) 阿茲海默症之治療藥物 18
三、山胡椒 (Litsea cubeba Persoon) 22
(一) 山胡椒介紹 22
(二) 山胡椒果實精油之成分分析 22
(三) 山胡椒之生理活性 26
四、褪黑激素 (Melatonin) 30
五、研究動機與架構 32
第三章 材料與方法 35
一、實驗儀器及藥品 35
(一) 實驗儀器 35
(二) 藥品 36
(三) 酵素免疫分析套組 37
(四) 動物實驗材料 37
二、實驗方法 38
(一) 山胡椒果實之一般成分分析 38
(二) 山胡椒果實精油之分析 39
(三) 改善小鼠記憶及學習能力之試驗模式建立 41
(四) 皮爾森相關係數 (Pearson correlation coefficient) 53
(五) 統計分析 54
第四章 結果與討論 55
一、台灣不同地區山胡椒果實之一般成分分析 55
二、台灣不同地區山胡椒果實於不同生長環境之精油含量比較 55
三、台灣不同地區山胡椒果實精油之GC/MS分析 55
四、台灣不同地區山胡椒果實精油之色澤及香氣特性差異 61
五、台灣不同地區山胡椒果實精油之主成分分析 61
六、山胡椒果實粉末改善Aβ1-40誘導小鼠認知障礙之成效 67
(一) 台灣南投清流部落山胡椒果實之一般成分分析及精油組成 67
(二) 類澱粉蛋白誘導手術與餵食山胡椒果實粉末對於小鼠體重及攝食量之影響 67
(三) 餵食山胡椒果實粉末對以類澱粉蛋白誘導類阿茲海默症小鼠血清生化參數之影響 67
(四) 餵食山胡椒果實粉末對以類澱粉蛋白誘導類阿茲海默症小鼠臟器組織體重相對重量之影響 73
(五) 餵食山胡椒果實粉末對以類澱粉蛋白誘導類阿茲海默症小鼠肝及腎臟組織之影響 73
(六) 餵食山胡椒果實粉末對以類澱粉蛋白誘導類阿茲海默症小鼠腦組織之影響 75
(七) 餵食山胡椒果實粉末對以類澱粉蛋白誘導類阿茲海默症小鼠記憶及學習能力之影響 75
(八) 餵食山胡椒果實粉末對以類澱粉蛋白誘導類阿茲海默症小鼠腦中丙二醛濃度之影響 87
(九) 餵食山胡椒果實粉末對以類澱粉蛋白誘導類阿茲海默症小鼠腦中蛋白質羰基氧化物濃度之影響 90
(十) 餵食山胡椒果實粉末對以類澱粉蛋白誘導類阿茲海默症小鼠腦中磷酸化-蛋白含量之影響 93
(十一) 餵食山胡椒果實粉末對以類澱粉蛋白誘導類阿茲海默症小鼠腦中Aβ斑塊沉積量影響 93
(十二) 餵食不同劑量之山胡椒果實粉末與小鼠行為能力試驗及腦中氧化壓力及阿茲海默症相關病徵之皮爾森相關係數 97
第五章 結論 101
第六章 參考文獻 103

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