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研究生:劉曲婷
研究生(外文):Chu-Ting Liu
論文名稱:高氏柴胡乙醇萃取物及其超臨界二氧化碳區分物之抗氧化與保肝活性之影響
論文名稱(外文):The Antioxidative and Hepatoprotective Effects of Ethanolic Extract from Bupleurum kaoi Liu, Chao et Chuang and Its Fractionations From Supercritical Carbon Dioxide
指導教授:曾慶瀛曾慶瀛引用關係王璧娟
指導教授(外文):Chin-Yin Tseng, Ph.D.Be-Jen Wang, Ph.D.
學位類別:碩士
校院名稱:國立嘉義大學
系所名稱:食品科學系碩士班
學門:農業科學學門
學類:食品科學類
論文種類:學術論文
論文出版年:2002
畢業學年度:90
語文別:中文
論文頁數:155
中文關鍵詞:高氏柴胡超臨界二氧化碳區分抗氧化四氯化碳初代肝細胞保肝
外文關鍵詞:Bupleurum kaoisupercritical carbon dioxidefractionationantioxidantcarbon tetrachlorideprimary hepatocyteshepatoprotective
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本研究探討高氏柴胡 (Bupleurum kaoi Liu, Chao et Chuang) 經過超臨界二氧化碳區分後各區分物之抗氧化與保肝能力。乙醇與高氏柴胡以4:1 (v/w) 混合經24小時萃取後得高氏柴胡乙醇萃取物E (ethanol extract),再進行超臨界二氧化碳區分,區分條件如下:溫度40 ℃,壓力分別為20、15、10及5 Mpa得殘留物R、區分物1 (F1)、區分物2 (F2) 及區分物3 (F3)。分析高氏柴胡乙醇萃取物與四種區分物之總多酚類含量及抗氧化能力。結果顯示,抗氧化力與清除1,1-二苯基-2-苦味肼基團 (DPPH‧) 自由基的能力,隨著區分物濃度的增加而增加。各區分物在10 mg/mL濃度時抑制丙二醛 (MDA) 生成的能力依次為E (73.54 %)、R (43.68 %)、F1 (40.90 %)、F2 (70.04 %) 及F3 (80.78 %)。而清除DPPH自由基的能力為E (58.63 %)、R (76.25 %)、F1 (53.27 %)、F2 (71.14 %) 及F3 (64.84 %)。當區分物濃度為5 mg/mL時,對超氧陰離子自由基生成的抑制率可達52 %以上,而區分物濃度為10 mg/mL時,清除超氧陰離子自由基的能力皆大於90 %。至於捕捉羥自由基方面,以F3的捕捉率 (68 %) 為最佳。區分後使F3的總酚類與類黃酮含量增加。由體外抗氧化能力得知F3的抑制超氧陰離子自由基生成、清除超氧陰離子自由基及捕捉羥自由基能力最強,F2其次。E抑制MDA生成的作用最佳而R清除DPPH自由基的能力最好。
高氏柴胡超臨界區分物對不同肝損傷誘導劑保肝能力之探討,用大鼠初代肝細胞經分離後以四種誘導劑如四氯化碳 (carbon tetrachloride; CCl4)、三丁基羥基過氧化物 (tert-butylhydroperoxide; t-BHP)、對位乙醯胺基酚 (acetaminophen; APAP) 與半乳糖胺 (D-galactosamine; D-GalN) 誘發肝細胞損傷,探討不同濃度0.1、0.3、0.5及1.0 mg/mL之高氏柴胡區分物保護四種誘導劑的肝細胞損傷模式中對大鼠初代肝細胞之保護作用。結果顯示不同的誘導劑所誘發肝細胞損傷的機制不同,故高氏柴胡區分物對大鼠肝細胞保護效果也不盡相同。總括而言在CCl4誘導的大鼠肝細胞損傷模式,顯示高氏柴胡區分物濃度於0.1及0.3 mg/mL低濃度即可對於CCl4誘導的肝損傷具保護效果; 肝細胞存活率在50 %以上 (p<0.05)。而低濃度區分物時 (0.1 mg/mL) 以F2對APAP與D-GalN 誘導大鼠肝細胞毒性時,保肝效果最顯著 (p<0.05)。
配合CCl4誘發大鼠急性肝炎模式,探討不同濃度 (100及500 mg/kg bw) 的高氏柴胡超臨界二氧化碳區分物對大鼠體內血清轉胺酵素 (SGOT 與SGPT)、脂質過氧化、抗氧化酵素 (SOD及Catalase) 與麩胱甘肽相關酵素 (GPx、GRd 及GST) 活性之影響。結果顯示,在血清轉胺酵素方面,大鼠注射CCl4後,其SGOT與SGPT值明顯增加 (p<0.05),而E、R、F1及F2於100及500 mg/kg bw下能降低SGOT與SGPT值,但F2 100 mg/kg bw及F3除外 (p<0.05)。肝臟中的脂質過氧化方面以誘導組的脂質過氧化物MDA為最高 (p<0.05),然而E、R及F1於100 mg/kg bw和E、R、F1及F2於500 mg/kg bw皆可減少MDA的生成量。另一方面,誘導組血球與肝臟中的抗氧化酵素及麩胱甘肽相關酵素活性會呈現代償性的增加,而誘導組大鼠肝臟中GRd活性顯著的降低 (p<0.05),餵食E 100、R 100、R 500、F1 500及F2 500 mg/kg bw可抑制GRd活性。透過CCl4誘發大鼠急性肝炎實驗模式篩選較具有保肝效果的高氏柴胡超臨界二氧碳區分物,總括來說以E、R及F1的保肝效果為最佳,F2其次,而F3的保肝效果不顯著。
This research studies the effects of Bupleurum kaoi Liu, Chao et Chuang fractionationed by supercritical carbon dioxide on the antioxidant and hepatopective abilities. Bupleurum kaoi was mixed with ethanol at the ratio 1:4 (v/w) for 24 hrs to obtain Bupleurum kaoi ethanol extract (E). The extract E was further fractionated by SC-CO2 at the following operation conditions: temp at 40 ℃ and pressure at 20, 15,10, or 5 MPa to give residue (R), fractionation 1 (F1), fractionation 2 (F2), or fractionation 3 (F3), respectively. The evaluation of total phenolic acid contents and the antioxidant ability of extract E and four fractionations showed that the antioxidant ability and the scavenge effect of 1,1-diphenyl-2-picryl hydrazyl (DPPH‧) radical increased with the concentrations of fractionations. The inhibition on malondialdehyde (MDA) formation and the scavenge effect on DPPH radical of Bupleurum kaoi extract and fractionations at 10 mg/mL were E (73 %), R (43 %), F1 (40 %), F2 (70 %), F3 (80 %) and E (58 %), R (76 %), F1 (53 %), F2 (71 %), F3 (64 %), respectively. When the concentration was 5 mg/mL, Bupleurum kaoi fractionations had above 52 % inhibition effect on the O2‧─ formation; however, when the concentration was 10 mg/mL, Bupleurum kaoi fractionations had over 90 % scavenge effect on the O2‧─. The effects on ‧OH trapping of fractionations from Bupleurum kaoi was not excellent except F3 (68 %). Fractionation altered the composition distributions such as increasing total polyphenols contents and total flavonoid contents of F3. From this in vitro antioxidation study, the abilities of F3 on inhibition superoxide anion radicals, scavenge superoxide anion radicals, and ‧OH trapping was the best and F2 was next among the fractionations. However, E was the best on inhibition MDA formation and R was the best on scavenge DPPH radical.
The various concentrations (0.1, 0.3, 0.5, or 1.0 mg/mL) of Bupleurum kaoi fractionations protected the primary hepatocytes against toxicity induced by one of the following reagents:carbon tetrachloride (CCl4), tert-butylhydroperoxide (t-BHP), acetaminophen (APAP) or D-galactosamine (D-GalN). The result displayed that the various hepatic toxicity induced reagents had different mechanisms for hepatocytes damage; thus, the heptoprotection effects of Bupleurum kaoi fractionations on induced reagents were variable. The Bupleurum kaoi fractionations at the concentrations of 0.1 and the 0.3 mg/mL were significantly decreased the cytotoxicity induced by CCl4. The survival cells were above 50 % (p<0.05). F2 even though at low concentration such as 0.1 mg/mL, was significant against the heptotoxicity induced by APAP and D-GalN (p<0.05).
Fit CCl4 induce impatient hepatitis mode of rats, study the propolis of supercritical carbon dioxide of the different concentration (100 and 500 mg/kg bw) fractionation the serum transaminases concentration on the hepatoprotective effect of Bupleurum kaoi fractionation by SC-CO2 against acute liver damage in rat, on the activities of lipid oxidation by CCl4-induced acute in rat liver, the antioxidation enzymes (SOD and Catalase) and the glutathione-related enzymes (GPx, GRd and GST) activity. The result of the rats injected by CCl4 on the serum transaminases, its SGOT and SGPT significantly increase (p<0.05). However E, R, F1 and F2 in the 100 and 500 mg/kg bw were lower the SGOT and SGPT all worth (p<0.05) except F2 in the 100mg/kg bw and F3. On the lipid proxidantive within liver aspect that TBARS value of induced group was most (p<0.05), however the TBARS''s value of E, R and F1 can reduce all in the 100 mg/kg bw and E, R, F1 and F2 in the 500 mg/kg bw. On the other hand, the related enzymes of the blood cell and the liver of the induced group on antioxidation enzymes and glutathione activity can present the increase (p<0.05) of free back, however the GRd activity of induced group liver set inside gross step down (p<0.05), then feed on the E 100, E 500, R 100, R 500 F1 500 and F2 500 mg/kg bw can inhibitioned on the GRd activity. Through the experiment mode of hepatitis on the CCl4 induced rats to screen the Bupleurum kaoi of supercritical carbon dioxide of effective on hepatoprotection to fractionation. In brief, the hepatoprotection effect of the E, R and F1 was the best, F2 is the next in order, however the F3''s hepatoprotective effect was ineffective.
摘 要………………………………………………………………i
Abstract……………………………………………………………iv
目 錄………………………………………………………………vii
表 次………………………………………………………………xi
圖 次…………………………‥…………………………………xiv
文獻整理
壹、活性氧及自由基之來源及氧化傷害………………………‥1
一、生物系統中脂質的氧化作用…………………………………1
二、自由基與活性氧之種類………………………………………2
三、活性氧之來源…………………………………………………9
四、活性氧傷害的疾病……………………………………………13
五、人體抵抗自由基的防禦系統…………………………………16
貳、不同肝損傷誘導劑的作用機制………………………………24
一、肝臟的功能與肝疾病…………………………………………24
二、不同肝損傷誘導劑的作用機制………………………………25
參、抗氧化與保肝活性之測定……………………………………33
一、抗脂質過氧化活性測定………………………………………33
二、清除1,1-二苯基-2-苦味肼基團 (1,1-diphenyl-2-picryl hydrazyl;DPPH) 自由基之能力…………………………………35
三、超氧陰離子自由基生成抑制之活性評估.…………………37
四、清除超氧陰離子能力之評估…………………………………38
五、對羥自由基之捕捉效應………………………………………40
肆、柴胡皂素之生理功效…………………………………………42
伍、超臨界二氧化碳區分…………………………………………50
本研究目的與實驗設計……………………………………….53
第一部份、高氏柴胡乙醇萃取物及其超臨界二氧化碳區分物抗氧化能力之探討…………………...55
摘 要………………………………………………………………56
前 言………………………………………………………………57
材料與方法…………………………………………………………59
一、藥品……………………………………………………………59
二、高氏柴胡之乙醇萃取及其超臨界二氧化碳區分……………60
三、總酚含量之測定………………………………………………60
四、類黃酮含量之測定……………………………………………61
五、對氯化亞鐵-抗壞血酸誘發鼠肝均質液脂質過氧化作用之‥61
六、清除1,1-二苯基-2-苦味肼基團 (1,1-diphenyl-2-picryl hydrazyl;
DPPH)能力測定……………………………………………‥62
七、超氧陰離子自由基生成抑制率之評估………………………63
八、清除超氧陰離子能力之評估…………………………………63
九、對氫氧自由基之捕捉效應……………………………………64
十、統計分析………………………………………………………64
結果與討論…………………………………………………………66
結 論………………………………………………………………73
第二部份、高氏柴胡乙醇萃取物及其超臨界二氧化碳區分物對誘導劑誘發大鼠初代肝細胞損傷的保肝用……………………………………86
摘 要………………………………………………………………87
前 言………………………………………………………………88
材料與方法…………………………………………………………90
一、藥品……………………………………………………………90
二、高氏柴胡乙醇萃取及其超臨界二氧化碳區分………………90
三、實驗動物………………………………………………………91
四、大鼠初代肝細胞之分離及培養………………………………91
五、分餾物對誘導劑保肝作用評估………………………………92
六、統計分析………………………………………………………93
結果與討論…………………………………………………………94
結 論………………………………………………………………100
第三部份、高氏柴胡乙醇萃取物及其超臨界二氧化碳區分物對四氯化碳誘發大白鼠急性肝炎之保肝活性……………………………………105
摘 要………………………………………………………………106
前 言………………………………………………………………107
材料與方法…………………………………………………………110
一、藥品……………………………………………………………110
二、高氏柴胡之乙醇萃取及超臨界二氧化碳區分………………111
三、實驗動物………………………………………………………111
四、四氯化碳誘發大鼠肝臟損傷…………………………………111
五、血液及肝臟樣品之前處理……………………………………112
六、血清轉胺酵素之活性分析……………………………………112
七、肝臟脂質過氧化之分析………………………………………113
八、麩胱甘肽相關酵素活性之測定………………………………113
九、抗氧化酵素活性之分析………………………………………114
十、蛋白質定量分析………………………………………………115
十一、肝臟組織觀察………………………………………………115
十二、柴胡皂素含量之測定………………………………………115
十三、統計分析……………………………………………………116
結果與討論…………………………………………………………117
結 論………………………………………………………………123
總結論………………………………………………………………134
參考文獻……………………………………………………………135
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