本研究以紅藻龍鬚菜 (Gracilaria tenuistipitata)作為探討。將藻體以鹼性蛋白酶水解後脫鹽再以超過濾處理後凍乾，即為GPHGU (Ultrafiltrated GPHG)。在抗疲勞實驗顯示餵食GPHGU有效延長小鼠負重游泳的時間 (116.3%)。此外，GPHGU顯示抗氧化活性，包含清除DPPH、ABTS自由基能力以及質體DNA氧化傷害保護能力，在GPHGU為15 mg/mL時，ABTS自由基能力達91.9%，而GPHGU為20 mg/mL時，DNA氧化傷害保護能力為36%。此外GPHGU對癌細胞Ca9-22顯示有抑制增生效應(IC50為10.43 mg/ml)。以陰離子交換層析結果顯示，眾區分物中，以A區在ABTS自由基清除能力 (86.6%)及質體DNA氧化傷害保護 (41%)最佳。以A區分物再利用逆相高效能液相層析之C18管柱與移動相梯度分離得七個區分物，其中以區分物3及6抗氧化活性較高，而區分物6在疏水性胺基酸、必需胺基酸與支鏈胺基酸的含量皆比區分物3高，推測區分物6胜肽，具有較好的生物活性與保健效果潛力。

Red algae Gracilaria tenuistipitata was investigated in this thesis. Algae samples were hydrolyzed by alkaline protease, precipitated and desalted to obtain GPH (Gracilaria tenuistipitata protein hydrolysate). After GPH was hydrolysated by gastrointestinal enzymes, samples (GPHG) were ultrafiltrated and then freeze-dried, called GPHGU (ultrafiltrated GPHG). Afterward, the anti-fatigue experiment was carried out. It showed that animals fed with GPHGU effectively prolonged swimming time in the weight-loaded forced tests (116.3%). The antioxidant activities of GPHGU (including DPPH radical scavenging, ABTS radical scavenging, and oxidative damage of plasmid DNA) were conducted. At GPHGU of 15 mg/ml, the ability of ABTS radical scavenging reached 91.9%. In addition, at GPHGU of 20 mg/ml, the protection (%) of DNA oxidative damage was 36%. Moreover, GPHGU exhibited the anti-proliferation of cancer cells Ca9-22 with an IC50 at 10.43 mg/ml. Among many fractions from GPHGU were separated by a DEAE anion exchange chromatography, the fraction A showed noticeable ABTS free radical scavenging (86.6%) and protection of DNA oxidative damage (41%). Afterward, seven partitions from the fraction A were obtained by using a C18 column of reverse phase high performance liquid chromatography with a mobile phase gradient. Among them, fraction 3 and 6 had higher antioxidant activity. However, fraction 6 exhibited a higher content of hydrophobic amino acids, essential amino acids, and branched chain amino acids than fraction 3. It is presumed that fraction 6 displays bio-active potential and possible health effects.

摘要 I
Abstract II
致謝 IV
目錄 V
圖目錄 VIII
表目錄 X
縮寫表 XI
壹、前言 1
貳、文獻回顧 3
一、海藻 (Seaweeds) 3
(一)、簡介 3
(二)、組成成分 4
(三)、藻類萃取物之生物活性 4
(四)、藻類之現況及應用 5
二、海龍鬚菜 (Gracilaria tenuistipitata) 8
(一)、分類 8
(二)、簡介 9
三、生物活性胜肽 11
(一)、簡介 11
(二)、食物來源的活性胜肽 12
四、疲勞之簡介 18
(一)、簡介 18
(二)、胜肽與抗疲勞之相關研究 19
五、鱗狀上皮口腔癌細胞 23
(一)、簡介 23
(二)、細胞週期 25
參、材料與方法 27
一、實驗材料 27
(一)、樣品來源 27
(二)、蛋白質水解酵素 27
(三)、鱗狀上皮口腔癌細胞 27
(四)、DNA質體 27
二、實驗藥品及儀器 27
(一)、實驗藥品 27
(二)、實驗儀器 31
三、實驗架構 33
(一)、海龍鬚菜硫酸銨沉澱蛋白質水解物 33
(二)、GPHGU之製備、分析與純化 34
四、實驗方法 35
(一)、海龍鬚菜之前處理與儲存 35
(二)、海龍鬚菜一般成分分析 35
(三)、海龍鬚菜蛋白水解物之製備 38
(四)、海龍鬚菜硫酸銨沉澱物之製備 38
(五)、海龍鬚菜硫酸銨沉澱物脫鹽 39
(六)、腸胃道酵素水解與超過濾 40
(七)、動物試驗 41
(八)、陰離子交換管柱層析 42
(九)、胺基(amino group)含量測定OPA (o-Phthalaldehyde)法 43
(十)、質體DNA保護試驗 44
(十一)、ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid))自由基清除能力分析 45
(十二)、DPPH (2,2-Dipheny-1-picrylhydrazyl)自由基清除力分析 47
(十三)、細胞試驗 48
(十四)、逆向HPLC管柱分析 50
(十五)、胺基酸組成分析 50
(十六)、統計分析 51
肆、實驗結果與討論 52
一、海龍鬚菜一般成分分析 52
二、GPHG及GPHGU之產率 54
三、動物試驗 55
四、海龍鬚菜蛋白之自由基清除活性探討 58
(一)、質體DNA保護試驗 58
(二)、ABTS自由基清除能力分析 62
(三)、DPPH 自由基清除能力分析 66
五、GPHGU對ICR小鼠存活影響與Ca9-22口腔癌細胞抗增生現象 68
六、GPHGU之分離純化 72
七、GPHGU之分離純化與抗氧化機能性探討 74
八、GPHGU-A之分離純化與抗氧化機能性探討 79
九、3及6區分物胺基酸組成分析 82
伍、結論 85
陸、參考文獻 86

圖目錄
圖 2-1、海龍鬚菜圖 9
圖 3-1、海龍鬚菜硫酸銨沉澱蛋白質水解物之實驗流程圖 33
圖 3-2、GPHGU之製備、分析與純化之實驗流程圖 34
圖 4-1、GPHGU對小鼠體重的影響 56
圖 4-2、GPHGU對小鼠強迫游泳時間的影響 57
圖 4-3、GPH對質體DNA誘發性氧化傷害保護效應 59
圖 4-4、GPHG對質體DNA誘發性氧化傷害保護效應 60
圖 4-5、GPHGU對質體DNA誘發性氧化傷害保護效應 61
圖 4-6、GPH之ABTS自由基清除能力 63
圖 4-7、GPHG之ABTS自由基清除能力 64
圖 4-8、GPHGU之ABTS自由基清除能力 65
圖 4-9、GPHGU之不同濃度DPPH自由基清除率 67
圖 4-10、GPHGU對細胞之存活率分析 70
圖 4-11、GPHGU對細胞之週期變化 71
圖 4-12、GPHGU之陰離子交換管柱層析 (DEAE) 73
圖 4-13、GPHGU-A對質體DNA誘發性氧化傷害保護效應 75
圖 4-14、GPHGU-C對質體DNA誘發性氧化傷害保護效應 76
圖 4-15、GPHGU-A之ABTS自由基清除能力 77
圖 4-16、GPHGU-C之ABTS自由基清除能力 78
圖 4-17、GPHGU-A之經逆向高效能液相層析(C18)分離之圖譜 80

表目錄
表 2-1、海藻之生物活性 6
表 2-2、海藻之機能特性 7
表 2-3、生物活性胜肽:抗氧化肽與抗菌肽 16
表 2-4、生物活性胜肽:抗高血壓肽與抗發炎肽 17
表 2-5、食物來源的抗疲勞胜肽 22
表 3-1、各百分飽和濃度硫酸銨添加量 39
表 4-1、海藻凍乾後之一般成分分析 53
表 4-2、GPHGU-A 各個區分物之ABTS自由基清除能力 81
表 4-3、區分物3及6之胺基酸組成(%) 84

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