臺灣博碩士論文加值系統

黑豆屬豆科（Leguminosae），含有必須胺基酸、不飽和脂肪酸、異黃酮、花青素、維生素E和皂素等活性成分。黑豆種皮具有良好的抗氧化能力，矢車菊素-3-葡萄糖苷(Cyanidin-3-O-glucoside；C3G)為種皮組成的重要成分。由於本實驗室先前研究指出黑豆具有護肝功效，故本研究將以四氯化碳（carbon tetrachloride, CCl4）誘導ICR小鼠急性肝損傷，探討黑豆種皮、種仁熱水萃取物（100 ℃, 20 min）與C3G對於急性肝損傷之影響；研究目的：(1) 了解黑豆護肝效能是來自於其種皮或者種仁，(2) 得知C3G是否為黑豆的護肝功能性成份。ICR小鼠試驗分為六組：分別為控制組（distilled water）、負控制組（0.3 % CCl4, 9 g/kg bw）、C3G組（55 mg/kg bw）、種仁水萃物組（SKWE, 200 mg/kg bw）、種皮水萃物組（SCWE, 200 mg/kg bw）與正對照組（silymarin, 200 mg/kg bw）。試驗為期一周，管餵小鼠C3G、種皮及種仁水萃物連續七天，再利用腹腔注射CCl4誘導肝損傷。結果發現，CCl4誘導之後負控制組小鼠血液中天門冬胺酸轉胺酶（AST）與丙胺酸轉胺酶（ALT）活性顯著性提高，當給予C3G、SCWE與SKWE皆能有效將低血液AST與ALT活性；尤其SCWE抑制血液ALT活性優於silymarin。急性肝損傷亦導致小鼠肝臟中超氧歧化酶（superoxide dismutase, SOD）、麩胱甘肽過氧化酶（glutathione peroxidase, GPx）與麩胱甘肽硫轉移酶（glutathione-s-transferase , GST）活性下降及麩胱甘肽（glutathone, GSH）濃度消耗。管灌SCWE或SKWE皆能提升GPx抗氧化酶活性、GST解毒酵素活性及GSH濃度，其中SKWE亦能提升小鼠肝臟總抗氧化能力；SCWE可抑制GSSG生成並增加GSH/GSSG比值，此外，餵食C3G與SCWE皆能抑制肝臟過氧化物生成。以上結果顯示，C3G、黑豆種皮與種仁熱水萃取物皆能減緩CCl4誘導的急性肝損傷。進一步使用80%乙醇（0.1% 醋酸）萃取黑豆種皮（BCE）評估乙醇萃取物的護肝功效是否可再提昇。BCE之C3G、Delphinidin-3-O-glucoside chloride、總多酚類、總花青素、縮合丹寧與總類黃酮的濃度皆顯著性高於SCWE；抗氧化活性（DPPH自由基清除能力、總抗氧化能力及還原力）也呈相同之趨勢。以相同動物試驗評估BCE護肝效能，結果顯示給予高（1000 mg/kg）、低劑量（200 mg/kg）BCE都能顯著性降低小鼠血液ALT活性，亦可分別提昇抗氧化酶GPx或Catalase活性；抑制肝臟GSSG濃度、降低氧化壓力指數與丙二醛（malondialdehyde）濃度。相較負控制組，餵食高劑量組能有效減少肝臟reactive oxygen species（ROS）含量。然而，CCl4誘導肝指數AST上升與肝臟GSH濃度消耗都無法透過管灌BCE獲得到改善。綜觀以上結果，黑豆之C3G、種皮與種仁皆具有護肝效能。相較下，黑豆種皮乙醇萃取物（BCE）之護肝效能較SCWE差，故推測除了花青素與類黃酮之外熱水萃取液（SCWE）仍有其他活性成分，目前得知SCWE多醣類可能為BCE所不具備的成份，黑豆種皮是否還具有其他護肝活性成份仍須進一步探討。

Black soybeans, belonging to of the family of Leguminosae, are abundant in essential amino acids, unsaturated fatty acids, isoflavones, anthocyanins, tocopherols and saponin. The seed coat of black soybean contains high amount of anthyocyanins and exhibits strong antioxidant activity and the major anthyocyanins of the seed coat is cyanidin-3-O-glucoside (C3G). Our previous research indicated that hot water extract of black soybean had hepatoprotective activity, the purpose of this study was to investigate the hepatoprotective effects of pure C3G, hot water extract from black soybean seed coat (SCWE) and seed kernel (SKWE) on carbon tetrachloride (CCl4)-induced acute liver damage. We were eagered to (1) confirm whether the predominant hepatorprotection of black soybean was provided from the seed coat extract or seed kernel extract, (2) to clarify whether C3G involved in the hepotoprotective activity of black soybean. ICR mice were investigated with six experimental groups: control group (distilled water), model group (0.3 % CCl4, 10 ml/kg bw), pure C3G group (55mg/kg bw), seed kernel hot water extract group (SKWE), seed coat hot water extract group (SCWE, 200 mg/kg) and silymarin (200 mg/kg) group serving as a positive control. During a week experiment, the mice were orally administrated with C3G, SCWE, and SKWE as well as silymarin for seven consecutive days prior to the intraperitoneal injection of CCl4 induced hepatic damage. The model group showed sudden increases of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities indicating acute liver damage induced by CCl4. However, C3G, SCWE and SKWE administration could significantly reduced serum AST and ALT activities in CCl4-treated mice; especially SCWE treatment exhibited a much better performance than silymarin in ALT’s reduction. The administration of CCl4 reduced the activities of superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione-s-transferase (GST) and the content of glutathione (GSH). Oral administration of SCWE or SKWE enhanced GPx and GST enzyme activity, as well as also the GSH concentration in CCl4-intoxicated mice. SKWE could also significantly increase trolox equivalent antioxidant capacity (TEAC) in the liver; SCWE significantly decreased hepatic glutathione disulfide (GSSG) content, while GSH/GSSG ratio was significantly increased. In addition, both pure C3G and SCWE treatment effectively inhibited hepatic malondialdehyde (MDA) formation. These results indicate that pure C3G, the hot water extract from the seed coat and seed kernel of black soybean has a protective effect against CCl4-induced hepatotoxicity in mice. Furthermore, we expected the hepatoprotective activity of the seed coat might be enhanced by extracting more anthocyanins using 80% ethanol (0.1% acetic acid) solution. The seed coat ethanol extract (BCE) exhibited much higher C3G, delphinidin-3-O-glucoside chloride, total phenol content, total anthocyanin content, condensed tannin content and total flavonoid content, as well as the antioxidant activity (DPPH radical scavenging activity, TEAC and reducing power) than SCWE. We used the same animal model to investigate the hepatoprotective effect of BCE against CCl4-induced acute liver damage. The results showed that both high (1000mg/kg) and low dose (200mg/kg) of BCE significantly reduced the increase of serum of ALT level, enhanced the GPx or catalase activity, inhibited the extent of hepatic GSSG concentration, oxidative stress index, as well as MDA formation in CCl4–treated mice. Moreover, BCE at high dose-treatment significantly weakened hepatic reactive oxygen species (ROS) level compared with the negative group. However, the high level of serum AST and GSH depletion in the liver after CCl4 treatment could not ameliorated by BCE administration. To sum up, both the seed coat and seed kernel portion contributed considerably to the hepatoprotective activity of black soybean. The seed coat ethanol-extract (BCE) showed a weak hepatoprotective activity when compared to the hot water extract (SCWE), so we suggested besides anthocyanins it might have other liver-protective components in the SCWE. For future study, the activive components in black soybean need to be identified.

摘要 I
Abstract III
目錄 V
表目錄 VII
圖目錄 VIII
壹、緒言 1
貳、文獻回顧 2
黑豆 (Black Soybean) 2
黑豆的機能性成分與生理活性 3
黑豆與黃豆的營養價值比較 7
花青素（Anthocyanidin） 8
肝臟 (Liver) 13
四氯化碳（Carbon Tetrachloride, CCl4） 19
護肝機制（Mechnism of hepatoprotective activity） 22
參、材料與方法 25
一、實驗儀器 25
二、化學藥品 26
三、實驗架構圖 29
四、實驗材料 30
五、實驗方法 30
肆、結果與討論 50
實驗Ⅰ:矢車菊素-3-葡萄糖苷、黑豆種皮與種仁水萃物對CCl4誘導急性肝損傷之護肝效果 50
全黑豆、黑豆種仁與種皮的一般成分分析 50
黑豆種皮、種仁熱水萃取液之總多酚、總花青素與總類黃酮分析 50
黑豆種皮、種仁水萃物與純車菊素-3-葡萄糖苷對於小鼠體重、肝臟與相對重量之影響 51
黑豆種皮、種仁水萃物與純車菊素-3-葡萄糖苷對於肝功能指標之影響 52
黑豆種皮、種仁水萃物與純車菊素-3-葡萄糖苷對於肝臟抗氧化酵素與物質之影響 54
黑豆種皮、種仁水萃物與純車菊素-3-葡萄糖苷對於肝臟總抗氧化能力與脂質過氧化物之影響 57
黑豆種皮、種仁水萃物與純車菊素-3-葡萄糖苷對於肝臟組織之影響 60
黑豆種皮、種仁水萃物與純車菊素-3-葡萄糖苷的護肝效能主成分分析 61
實驗Ⅱ：黑豆種皮乙醇萃取物對CCl4誘導急性肝損傷之保護效果 62
黑豆種皮萃取物之抗氧化物質與抗氧化活性比較 62
黑豆種皮萃取物之花青素定性與定量 63
乙醇萃取物對於肝功能指標之影響 65
乙醇萃取物對於肝臟抗氧化酵素與物質之影響 66
乙醇萃取物對於肝臟脂質過氧化物與ROS含量之影響 69
乙醇萃取物對於肝臟組織之影響 71
黑豆種皮乙醇萃取物的護肝效能主成分分析 72
伍、結論 73
陸、參考文獻 99

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