臺灣博碩士論文加值系統

在蔬果中以生蒜的硫化物最多，這些不同的有機硫成份賦予了生蒜許多良好的生理活性，如抗氧化、抗腫瘤、抗發炎等，但也因這些硫化物成份而導致生蒜具有刺激性氣味，食用太多也可能造成腸胃不適，因此令許多人無法接受。近年來，在日本及韓國盛行將生蒜於特定溫溼度中發酵一個月以上，藉此來消除原本生蒜含有之刺激氣味，而衍生出黑蒜產品，其具有如同果乾般酸甜的口感，極被大眾所接受，已知其保留了生蒜原本有益之功效，且具更優異之抗氧化、抗發炎、抗過敏、抗癌、保護酒精性肝損傷以及降低血脂之效果。不過，現今對黑蒜之探討大多只侷限於經由高溫發酵，鮮少探討低溫發酵之成果。此外，低溫發酵之黑蒜在發酵過程中生理活性的變化亦所知不多。因此，本研究利用40 oC低溫與70% 濕度自行發酵黑蒜，並以8天為一個單位進行採收至40天，並佐以冷水及乙醇進行萃取，並藉由檢測發酵過程中黑蒜萃取物總多酚含量變化，並分析其對人類肝癌細胞之存活率影響及其作用機制，以探討黑蒜萃取物在低溫發酵過程中之生理活性變化。結果顯示，經由發酵後的黑蒜較生蒜具有較高之總多酚含量，其中又以黑蒜的乙醇萃取物最佳。且發酵後之黑蒜對人類肝癌細胞Hep-G2細胞亦具有較好之抑制效果；且對於小鼠肝細胞FL83B不具有毒殺作用。此外，我們發現Hep-G2細胞經冷水或乙醇萃取之黑蒜萃取物處理後能有效活化 BCl-2相關X蛋白 (BCL-2 Assaciated X protein, Bax)、半胱胺酸蛋白酶-3 (Cysteine asparate protease-3, Caspase-3)、半胱胺酸蛋白酶-9 (Cysteine asparate protease-9, Caspase-9)及 聚(ADP-核醣)聚合酶 (Poly〔ADP-ribose〕polymerase, PARP)，並抑制 B細胞淋巴瘤-2基因 (B-cell lymphoma 2, Bcl-2) 以及增殖細胞核抗原 (Proliferating Cell Nuclear Antigen, PCNA) 之表達，顯示冷水或乙醇之黑蒜萃取物能誘導Hep-G2細胞走向凋亡。因此，黑蒜產業之發展除了能妥善利用久放的生蒜，同時也具有開發作為抗癌藥物之潛能。

Garlic, a splices with abundant of organic sulfides, processes several physiological functions, such as anti-oxidant, anti-tumor, anti-inflammatory activities. However, the stimulatory ordor of raw garlic and causing gastrointestinal discomfort that is unacceptable to many people, since it rich in organic sulfides. Receutly, fermentation of garlic into black garlic by specific temperature and humidity for more than one month to eliminate it’s odor is prevalence in Japan and Korea. It is known that black garlic retains the original functions of the garlic, and has excellent anti-oxidation, anti-inflammation, anti-allergy, anti-cancer , hepatoprotective activities and hypolipidemic effect than garlic. Since the fermentation of garlic is the complex process, studies it’s mainly focus on the high temperature fermentation, but rarely explore the effect of physiological activity changes in the low temperature fermentation processes. Thus, we prepared the black garlic at 40oC in 70% humidity for 40 days which is divided into 8 intervals , followed by extraction with cold water and ethanol. The total polyphenol content and the anti-cancer effect of these extracts were than determined . Results showed that the cold water and ethanol extracts of black garlic had higher total total polyphenol content than those of raw garlic. Additionally, ethanol extracts showed the highest total phenol content. Moreover, black garlic extracts had better inhibitory effect on human hepatoma cells (Hep-G2) than garlic, and had no toxic effect on normal mouse hepatocyte (FL83B). Furthermore, we found that BCL-2 Assaciated X protein (Bax), Cysteine asparate protease-3 (Caspase-3), Cysteine asparate protease-9 (Caspase-9) and Poly 〔ADP-ribose〕 polymerase (PARP) protein was activated upon cold water or ethanol extracts of black garlic. Meanwhile, Bcl-2 and PCNA protein was inhibited. Taken together, our results indicated that the cold water or ethanol extracts of black garlic induce apoptosis via a mitochondria-depandent manner in Hep-G2 cells. Therefore, the development of black garlic can improve the garlic vale, and also develop as a new alternative medicine to treat hepatic carcinoma.

致謝 I
中文摘要 II
Abstract III
目錄 V
圖目錄 VIII
表目錄 IX
第一章、 前言 1
第二章、 文獻回顧 2
　　第一節、生蒜簡介 2
　　　　一、生蒜介紹 2
　　　　二、生蒜生長特性 3
三、生蒜品種 4
　　　　四、生蒜之機能性成分與生理活性 7
　　第二節、黑蒜簡介 11
　　　　 一、黑蒜介紹 11
二、黑蒜生理活性 11
　　第三節、肝癌介紹 14
　　第四節、細胞凋亡簡介 20
第三章、研究目的 23
第四章、材料與方法 24
　　第一節、實驗架構 24
　　第二節、化學試劑 25
　　第三節、儀器設備 27
　　第四節、實驗方法 28
　　　　一、生蒜來源 28
　　　　二、黑蒜製備 28
　　　　三、萃取方式 28
　　　　四、一般成份分析 29
　　　　五、褐變 31
　　　　六、總多酚含量測定 31
　　　　七、細胞培養 32
　　　　八、細胞存活率測定 32
　　　　九、蛋白質萃取 33
　　　　十、蛋白質濃度定量測定 33
　　　　十一、西方墨點法分析 35
　　　　十二、Casepase-3/7活性分析 36
　　　　十三、細胞週期分析 37
　　　　十四、統計分析 37
第五章、結果 38
　　第一節、生蒜一般成份分析 38
　　第二節、不同發酵天數之黑蒜褐變度分析 38
　　第三節、生蒜及不同發酵天數之黑蒜萃取物總多酚含量測定 39
　　第四節、生蒜及不同發酵天數之黑蒜萃取物對小鼠正常肝細胞存活率之影響 39
　　第五節、生蒜及不同發酵天數之黑蒜萃取物對肝癌細胞之存活率之影響 40
　　第六節、生蒜及不同發酵天數之黑蒜萃取物對人類肝癌細胞之細胞週期分析 41
　　第七節、生蒜及不同發酵天數之黑蒜萃取物對人類肝癌細胞之凋亡機制 42
第六章、討論 43
第七章、結論 48
第八章、參考文獻 49

圖目錄
Figure 1. 不同發酵天數黑蒜之褐變程度 62
Figure 2. 冷水及乙醇萃取不同發酵天數之黑蒜對人類肝癌細胞存活率之影響 64
Figure 3. 冷水及乙醇萃取不同發酵天數之黑蒜對小鼠正常肝細胞存活率之影響 66
Figure 4. 冷水及乙醇萃取不同發酵天數之黑蒜對肝癌細胞 Hep-G2 作用時間對細胞存活率之影響 68
Figure 5. 冷水及乙醇萃取不同發酵天數之黑蒜對肝癌細胞 Hep-G2 凋亡機制之探討 70
Figure 6. 冷水及乙醇萃取不同發酵天數之黑蒜對人類肝癌細胞 Hep-G2 細胞之 Caspase-3/7 活性析 73
Figure 7. 冷水及乙醇萃取不同發酵天數之黑蒜對人類肝癌細胞 Hep-G2 細胞週期之響 75

表目錄
Table 1. 生蒜之一般成份分析 60
Table 2. 冷水及乙醇萃取之黑蒜萃取物之總多酚含量測定 60
Table 3. 不同萃取之生蒜及黑蒜對肝癌 Hep-G2 細胞中半抑制濃度 (IC50) 61

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