臺灣博碩士論文加值系統

摘要
本研究乃欲探討杜仲葉水萃取物 (WEDZ)及其有效成分 (CHA與PCA)，以及決明子水萃取物 (WECT)對以CCl4誘導大鼠慢性肝損傷之護肝功效及抗氧化能力之評估。
WEDZ對管餵CCl4誘發大鼠慢性肝損傷之體重變化方面，CCl4會造成大鼠體重上升之速率減緩及肝腎相對重量增加，與正常組比具顯著性差異 (p < 0.05)；餵食WEDZ及其有效成分與負控制組比則能顯著 (p < 0.05)提高體重之上升速率及減低肝腎之相對重量。在血清生化值之結果顯示以CCl4誘導大鼠慢性肝損傷會致使GOT、GPT、LDH、ALP、-GT、BUN、TBil、Chol及TG顯著 (p < 0.05)高於正常組。餵食WEDZ及其有效成分與負控制組比則能顯著(p < 0.05)降低GOT、GPT、ALP、-GT、BUN及TG。在抗氧化能力評估方面，管餵CCl4誘發大鼠慢性肝損傷會造成肝臟及血清中GSH含量顯著下降及MDA顯著含量提高(p < 0.05)，餵食WEDZ及其有效成分與負控制組比則能顯著 (p < 0.05)提高GSH含量及降低MDA之生成。餵食WEDZ及其有效成分可提升肝臟中GPx、GRd、GST及SOD之酵素活性，以及提升血清中總抗氧化能力。由肝臟組織切片圖可發現餵食WEDZ及其有效成分可降低CCl4對大鼠誘發之肝細胞腫脹、淋巴球浸潤、細胞空泡化、肝細胞壞死及結締組織增生之情況。
在WECT之結果方面，CCl4的餵食會造成大鼠體重上升減緩及肝臟重量上升，餵食WECT能改善大鼠體重之上升速率，對肝臟重量之變化並無顯著影響 (p > 0.05)。在血清生化值方面，CCl4會導致血清中GOT、GPT及LDH酵素活性及TBil、Crea及Chol含量顯著 (p < 0.05)上升，餵食決明子水萃取物顯著能降低血清中GOT、GPT及LDH酵素活性及減低Crea之含量。在肝臟及血清之MDA及GSH含量上，WECT可降低MDA含量及提高GSH含量。在血清總抗氧化能力 (TEAC)之評估上，WECT可顯著 (p < 0.05)提升血清中之總抗氧化能力。由結果得知，WECT在CCl4誘導大鼠肝損傷模式中具有良好之肝臟保護的能力及提高生物體之抗氧化能力。由肝臟病理組織切片圖可得知餵食WECT可降低CCl4誘發之肝細胞霧狀腫脹、細胞空泡化、細胞氣球狀變性、及壞死細胞之生成。
由上述結果可得知，餵食大鼠WEDZ及其有效成分或WECT可顯著之降低肝臟損傷程度，並可顯著提升肝臟與血清中因CCl4誘導下降之抗氧化活性。因此推測WEDZ及其有效成分，與WECT應是阻斷CCl4對細胞之氧化傷害以達到保護肝臟損傷之效果。

Abstract
The aim of this study was to investigate the hepatic protection and antioxidation of water extract from Du-Zhong (Eucommia ulmoides Oliv.) leaves (WEDZ) (including its active compounds: chlorogenic acid and protocatechuic acid) and water extract of Cassia tora L. (WECT) against carbon tetrachloride (CCl4) induced hepatic damage in rats.
The oral treatment with WEDZ (0.1, 0.5 and 1.0 g/kg rat) for 28 consecutive days and the administration of CCl4 (0.5 mL/rat, 20%) induced hepatic damage in rats. It could find that CCl4 decrease the weight grain rate and increase the relative organ weights of liver and kidney, and treatment with WEDZ could significantly (p < 0.05) increase weight grain rate and decrease the relative organ weight of liver and kidney. In serum biochemical parameters, CCl4 induced rats liver damage could significantly (p < 0.05) increase the GOT, GPT, LDH, ALP, -GT, BUN, TBil, Chol and TG level as compared with normal control in serum. Treatment with WEDZ and its active compounds could decrease the GOT, GPT, LDH, ALP, -GT, BUN and TG level when compared with negative control. In antioxidant activity evaluation, administration of CCl4 induced rats liver damage caused the GSH content significantly (p < 0.05) decreased and MDA content increased (p < 0.05) both in liver and serum as compared with normal control. Treatment with WEDZ and its active compounds also could significantly increase (p < 0.05) the GSH content and decreased the MDA content both in liver and serum. Administration of WEDZ and its active compounds could increase the activites of GPx, GRd, GST and SOD, and the trolox equivalent antioxidant capacity (TEAC) in serum. Liver histopathology showed that WEDZ and its active compounds reduced the incidence of liver lesions including hepatic cells cloudy swelling, lymphocytes infiltration, cytoplasmic vacuolization, hepatic necrosis and fibrous connective tissue proliferated induced by CCl4 in rats.
The administration of CCl4 (0.5 mL/rat, 20%) induced hepatic damage could decrease the weight grain rate and increase the liver weight in rats. Administration of WECT could significantly (p < 0.05) increase the weight grain rate, but no significant different (p > 0.05) in rats organ weight. In serum biochemical parameters, CCl4 induced rats liver damage could significantly (p < 0.05) increase the GOT, GPT and LDH activities and TBil, Crea and Chol content as compared with normal control in serum. Treatment with WECT could significantly (p < 0.05) decrease the GOT, GPT and LDH activities, and decrease the Crea content. WECT could decrease the MDA content and increase GSH content both in liver and serum induced by CCl4. WECT could significantly (p < 0.05) increase the activites of GPx, GRd, GST, Cat and SOD decreased by CCl4. WETC could significantly (p < 0.05) increase the trolox equivalent antioxidant capacity (TEAC) in serum. Liver histopathology showed that WECT reduced the incidence of liver lesions including cloudy swelling, cytoplasmic vacuolization, ballooning degeneration and necrotic cell formation induced by CCl4 in rats.
The data suggest that oral administration with WEDZ and WECT for 28 consecutive days could significant decrease the hepatic damage level induced by CCl4 in rats. Moreover, WEDZ and WECT could increase the activites of antioxidant enzymes in liver and increase the total antioxidant capacity decrease by CCl4 in vivo to protect the liver damage.

目錄
中文摘要.................................................................................................. 1
英文摘要................................................................................................ 3
第一部分-前言……………………………………………………………………. 5
第二部分-文獻整理………………………………………………………….. 7
一、氧化壓力與疾病…………………………………………………… 8
(一)、自由基和活性氧的定義…………………………………….. 8
(二)、活性氧的種類…………………………………………………… 8
(三)、氧化狀態失調與疾病…………………………………………… 10
(四)、生物體內抗氧化防禦系統之介紹……………………………. 13
二、肝臟生理及其傷害機制..................................................... 15
(一)、肝臟的生理結構及功能……………………………………….. 15
(二)、肝損傷的機制…………………………………………………….. 17
(三)、CCl4導致肝傷害的機制……………………………………….. 19
(四)、護肝成分簡介……………………………………………………….. 22
三、杜仲葉與決明子之背景介紹………………….………………. 25
(一)、杜仲葉的相關研究資料……………………………………………. 25
(二)、決明子的相關研究資料………………………………………… 29
四、研究目的……………………………………………………………… 33
五、研究架構....................................................................................................... 34
(一)、杜仲葉水萃取物之動物實驗架構............................................. 34
(二)、決明子水萃取物之動物實驗架構...................................... 35
第三部分-材料與方法………………………………………………………….. 36
一、材料................................................................................................ 36
(一)、實驗動物…………………………………………………….. 36
(二)、樣品之來源………………………………………………….. 36
(三)、試藥……………………………………………………………. 36
二、方法…………………………………………………………………. 36
(一)、水萃物樣品之製備…………………………………………. 37
(二)、水萃取物樣品中有效成分之分析……………………………………… 37
(三)、動物實驗設計………………………………………………. 37
(四)、血清生化值檢測…………………………………………… 38
(五)、肝臟中抗氧化能力測定……………………………………. 40
(六)、血清中抗氧化能力測定……………………………………… 43
(七)、組織切片…………………………………………………….. 44
(八)、統計分析…………………………………………………… 44
第四部分-結果與討論………………………………………………………… 45
一、杜仲葉水萃取物 (WEDZ)之動物實驗……………………….. 45
(一)、WEDZ之產率…………………………………………….. 45
(二)、WEDZ中有效成分含量之分析……………………………. 45
(三)、大鼠體重變化………………………………………………… 45
(四)、大鼠臟器重量變化……………………………………….. 46
(五)、血清生化值…………………………………………………. 47
(六)、肝臟抗氧化能力及酵素活性評估……………………....... 51
(七)、血清抗氧化能力及抗氧化物質含量測定 55
(八)、肝組織切片H.E.染色……………………………………… 56
(九)、結論……………………………………………………….. 58
WEDZ動物實驗之圖表區……………………………… 59~76
二、決明子水萃取物(WECT)之動物實驗…………………………… 77
(一)、決明子水萃取物之產率………………………………….. 77
(二)、大鼠體重變化……………………………………………… 77
(三)、大鼠臟器重量變化……………………………..………… 77
(四)、血清生化值……………………………………………….. 78
(五)、肝臟抗氧化能力及酵素活性評估…………………………. 82
(六)、血清抗氧化能力及抗氧化物質含量測定………………… 85
(七)、肝組織切片H.E.染色………………………………………… 86
(八)、結論………………………………………………………… 88
WECT動物實驗之圖表區………………………………… 89~105
第五部分-總結論……………………………………………………………… 106
第六部分-參考文獻…………………………………………………………….. 107

參考文獻
王靖。1991。決明子治療高血脂症例近遠期療效觀察。遼寧中醫。18: 29。
胡康才和胡一鳴。1992。決明子茶臨床藥效觀察。浙江中醫。27: 432。
張文卿。1994。決明子丸治療大便祕結200例。遼寧中醫。18: 390。
許博文。2002。藥用植物動物之哉培與飼養。九洲圖書文物有限公司。p21-224。
趙振銘、張 麗、王義和與謝 皖。1999。復方決明子沖劑對大鼠血脂調節的研究。武警醫學。10(8): 435-437。
劉接寶。1982。臨床實用彩色科學中藥大典。立得出版社。p190-193。
顏焜熒。1985。常用中藥之炮製。南天出版社。p148。
Akila, G., Rajakrishnan, V., Viswanathan, P., Rajashekaran, K. N. and Menon, V. P. 1998. Effects of curcumin on lipid profile and lipid peroxidation status in experimental hepatic fibrosis. Hepatol. Res. 11: 147-157.
Anon, M. T., Ubeda, A. and Alcaraz, M. J. 1992. Protective effects of phenolic compounds on CCl4-induced toxicity in isolated rat hepatocytes. Z. Naturforsch. 47(3-4):275-279.
Arnao, M. B., Cano, A., Hernandez-Ruiz, J., Garcia-Canovas, F. and Acosta, M. 1996. Inhibition by L-ascorbic acid and other antioxidants of the 2.2''-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) oxidation catalyzed by peroxidase: a new approach for determining total antioxidant status of foods. Anal Biochem. 236(2): 255-61.
Arteel, G. E., Uesugi, T., Bevan, L. N., Gabele, E., Wheeler, M. D., McKim, S. E. and Thurman, R. G. 2002. Green tea extract protects against early alcohol-induced liver injury in rats. Biol. Chem. 383(3-4): 663-670.
Atanasiu, R.L., Stea, D. and Mateescu, M.A. 1998. Direct evidence of ceruloplasmin antioxidant properties. Mol. Cell Biochem. 189: 127-135.
Bellomo, G., Mirabelli, F., Dimonte, D., Richelmi, P., Thor, H.,Orrenius, C. and Orrenius, S. 1987. Formation and reduction of glutathione-mixed disulides during oxidative stress. Biochem. Pharmacol. 36: 1313-1320.
Boigk, G., Stroedter, L.,Herbst, H., Waldschmidt, J., Riecken, E. O. and Schuppan, D. 1997. Silymarin retards collagen accumulation in early and advanced biliary fibrosis secondary to complete bile duct obliteration in rats. Hepato. 26: 643-649.
Borek, C. 2001. Antioxidant health effects of aged garlic extract. J. Nutr. 131(3s): 1010S-1015S.
Borras, C., Sastre, J., Garcia-Sala, D., Lloret, A., Pallardo, F. V. and Vina, J. 2003. Mitochondria from females exhibit higher antioxidant gene expression and lower oxidative damage than males. Free Radic. Biol. & Med. 34(5): 546-552.
Bosch, J., D’amico, G., Luca, A., Gacia-Pagan, J. C., Feu, F. and Escorsell, A. 1998. Drug therapy for varuceal hemorrhage. Oxford: Blackwell Scientific Publishcations.108-123.
Buege, A. J. and Aust, S. D. 1978. Microsomal lipid peroxidation. Methods Enzmol. 52: 302-310.
Cai, Y. J., Ma, L. P., Hou, L. F., Zhou, B., Yang, L. and Liu, Z. L. 2002. Antioxidant effects of green tea polyphenols on free radical initiated peroxidation of rat liver microsomes. Chem. Phys. Lipids. 120(1-2): 109-117.
Carola, R., Harley, J. P. and Noback, C. R. 1990. Human anatomy and physiology. McGraw-Hill Inc.709-712.
Choi, J.S., Lee, H.J., Ha, J.O. and Kang, S.S. 1997. In vitro antimufagenic effects of anthraqunone aglycones and naphthopyrone glycosides frome Cassia tora. Plana Med. 63(1): 4-11.
Clement, B. H., Eonard, M., Rissel, M., Druguent, J. A., Grimand and Herbage, K. 1984. Cellular origin of collagen and fibronectin in the liver. Cell Mol. Neurobiol. 30: 489-496.
Coelho, H. S., Nogueira, C. A. V. and Silva, A. C. 2002. Relationship between gamma glutamyl transpeptidase (GGT) levels and treatment response in chronic hepatitis C. J. Hepatol. 36: 232.
Cohen, G., Dembiec D. and Marcus J. 1970. Measurement of catalase in tissue extracts. Anal. Biochem. 34: 30-38.
D’amico, G., Pagliaro, L. and Bosch, J. 1995. The treatment of portal hypertension: a meta- analytic review. Hepatol. 22: 322-354.
Davis, T. M., Binh, T. Q., Danh, P. T., Dyer, J. R., St John. A., Garcia-Webb, P. and Anh, T. K. 1994. Serum vitamin A and E concentrations in acute falciparum malaria: modulators or markers of severity? Clin. Sci. (Lond) 87(5): 505-511.
De la Iglesia, F., Sturgess J. M. and Feuer, G. 1982. New approaches for assessment of hepatotoxicity by means of quantitative functional-morphological interrelationship in toxicity of liver. Eds. G. L. Plaa and W. R. Hewitt. New York: Raven Press. Clarendon Press. Oxford. P. 23-28.
Duke, J.A. 1992. Handbook of phytochemical constituents of GRAS herbs and other ecomic plants. PP. 143-144. CRC press, Boca Raton, Fla.
Elhaimeur, F., Courderot-Masuyer, C., Nicod, L., Guyon, C., Richert, L. and Berthelot, A. 2002. Dietary vitamin C supplementation decreases blood pressure in DOCA-salt hypertensive male Sprague-Dawley rats and this is associated with increased liver oxidative stress. Mol. Cell Biochem. 237(1-2): 77- 83.
Gioli-Pereira, L., Coradin, K., Nagaoka, M. R., Borges, D. R. and Kouyoumdjian, M. 2002. Enzyme release from injured, preserved, and ex vivo reperfused liver does not indicate malfunction. Transplantation. 74 (8): 1081-1083.
Habig, W. H., Pabst, M. J. and Jakoby, W. B. 1974. Glutathione S-transferase: the first enzymatic step in mercapturic acid formation. J. Biol. Chem. 249: 7130-7139.
Halliwell, B. and Gutteridge, J.M.C. 1998. Antioxidant defense. Free Radicals in Biology and Medicine. pp. 105-245. Oxford University press Inc., New York.
Halliwell, B. 1994. Free radicals, antioxidants and human disease: curiosity, cause or consequence? Lancet 344: 721-723.
Halliwell, B. and Gutteridge, J. M. C. 1998. “Free Radicals in Biology and Medicine.” ed by B. Halliwell and J. M. C. Gutteridge. Clarendon Press. Oxford. P. 246-350.
Hanna, E. and Sherman, A.C. 1999. Quality-of-life issues in head and neck cancer. Current Oncology Reports 1: 124-128.
Hanna, P.M. and Mason, R.P. 1992. Direct evidence for inhibition of free radical formation from Cu(I) and hydrogen peroxide by glutathione and other potential ligands using the EPR spin-trapping technique. Archi. Biochem. Biophys. 295: 205-213.
Hashimoto, M., Kothary, P.C. and Raper, S.E. 1999. Phenobarital in comparison with carbon tetrachloride and Phenobarbital-induced cirrhosis in rat liver regeneration. J. Surg. Res. 81:164-169.
Hemmings, S. J., Pulga, V. B., Tran, S. T. and Uwiera, R.R. 2002. Differential inhibitory effects of carbon tetrachloride on the hepatic plasma membrane, mitochondrial and endoplasmic reticular calcium transport systems: implications to hepatotoxicity. Cell. Biochem. Funct. 20(1): 47-59.
Hemmings, S. J., Pulga, V. B., Tran, S. T. and Uwiera, R.R. 2002. Differential inhibitory effects of carbon tetrachloride on the hepatic plasma membrane, mitochondrial and endoplasmic reticular calcium transport systems: implications to hepatotoxicity. Cell. Biochem. Funct. 20(1): 47-59.
Hodge, G., Hodge, S. and Han, P. 2002. Allium sativum (garlic) suppresses leukocyte inflammatory cytokine production in vitro: potential therapeutic use in the treatment of inflammatory bowel disease. Cytometry. 48(4): 209-215.
Holdwn, P. R., James, N. H., Brooks, A. N., Robert, R. A., Kimber, I. and Pennies, W. D. J. 2000. Identification of a possible association between carbon tetrachloride- induced hepatotocixity and interleukin-8 expression. Biochem. Mol. Toxicol. 14: 283-290.
Horie, Y., Yamagishi, Y., Kato, S., Kajihara, M., Kimura, H. and Ishii. H. 2003. Low-dose ethanol attenuates gut ischemia/reperfusion-induced liver injury in rats via nitric oxide production. J. Gastroenterol. Hepatol. 18(2):211-7.
Hsieh, C.H. and Yen, G.C. 2000. Antioxidant actions of Du-Zhong (Eucommia ulmoides Oliv.) toward oxidative damage in biomolecules. Life Sci. Vol. 66 15:1387-1400.
Hu, M. L. 1994. Measurement of plasma protein thiopls and GSH. Methods Enzymol. 233: 380-385.
Ilavarasan, R., Anbazhagan, S. M. and Venkataraman, S. 2004. Antioxidant activity of Thespesia populnea bark extracts against carbon tetrachloride-induced liver injury in rats. J. Ethnopharmacol. 87: 227—230.
Kadiiska, M.B., Gladen, B.C., Baird, D.D., Dikalova, A.E., Sohal, R.S., Hatch, G.E., Jones, D.P., Mason, P.P. and Barrett, J.C. 2000. Biomarkers of oxidative stressstudy: Are plasma antioxidants markers of CCl4 poisoning? Free Radic. Biol. Med. 28: 838-845.
Kalantari, H. and Salehi, M. 2001. The protective effect of garlic oil on hepatotoxicity induced by acetaminophen in mice and comparison with N-acetylcysteine. Saudi. Med. J. 22(12): 1080-1084.
Karen, M. S. and Clarence, A. R. 1996. Surgical techniques for extravascular occlusion of intrahepatic shunts. Compend Contin. Educ. Small. Anim. Pract. 18: 745-754.
Kasahara, K., Nishikawa, A., Furukawa, F., Ikezaki, S., Tanakamaru, Z., Lee, I. S., Imazawa, T. and Hirose, M. 2002. A chronic toxicity study of josamycin in F344 rats. Food. Chem. Toxicol. 40 (7): 1017-1022.
Kim, S. G., Nam, S.Y., Chung, H.C., Hong, S.Y. and Jung, K.H. 1995. Enhanced effectiveness of dimethyl-4, 4’-dimethoxy-5,6,5’,6’,- dimethylene dioxylbiphenyl-2,2’-dicarboxylate in combination with garlic oil against experimental hepatic injury in rats and mice. J. Pharm. Pharmacol. 47:678-682.
Kono, Y., Kashine, S., Yoneyama, T., Sakamoto, Y., Matsui, Y. and Shibata, H. 1998. Iron chelation by chlorogenic acid as a natural antioxidant. Biosci. Biotechnol. Biochem. 62: 22-27.
Kuz’menko, D.I. and Laptev, B.I. 1999. Reserve of serum lipids for peroxidation during oxidative stress in rats. Voprosy Meditisinskoi Khimi 45: 47-52.
Kvasnička, F., Bíba, B., Ševčík, R., Voldřich, M. and Krátká, J. 2003. Analysis of the active components of silymarin. J. Chromatogr. A. 990: 239-245.
Lawerence, R. A., Burk, R. F. 1976.Glutathione peroxidase activity in selenium-deficient rats liver. Biochem. Biophys. Res. Commun.71: 952-958.
Lebrea, D. 1994. Pharmacological treatment of portal hypertension: hempdynamic effects and prevention of bleeding. Pharmacol. and Ther. 61: 65-107.
Letteron, P., Labbe, G., Degott, C., Berson, A., Fromenty, B., Delaforge, M., Larrey, D. and Pessayre, D. 1990. Mechanism for the protective effects of silymarin against carbon tetrachloride-induced lipid peroxidation and hepatotoxicity in mice. Biochem. Pharma. 39: 2027-2034.
Mak, D. H., Ip, S. P., Li, P. C., Poon, M. K. and Ko, K. M. 1996. Alterations in tissue glutathione antioxidant system in Streptozotocin-induced diabetic rats. Mol. Cell Biochem. 162: 153-158.
Martel, F., Martins, M. J., Hipólito-reis, C. and Azevedo, I. 1998. Postanal development of organic cation transport in the rat liver. Pharmacol. Res. 37 (2): 131-136.
McCord, J. M, and Fridovich, I. 1969. An enzyme function for erythrocuprein (hemocuprein). J. Biol. Chem. 244: 6049-6055.
McCord, J. M. 2000. The evolution of free radicals and oxidative stress. Am. J. Med. 108(8): 652-659.
Miller, N. J., Rice-Evans, C. Davies, M. j., Gopinathan, V. and Milner, M. 1993. A novel method for measuring antioxidant capacity and its application to monitoring the antioxidant status in premature neonates. Clin. Sci. 84: 407-412.
Millward, G. H. and Jezequel, A. M. 1985. Normal histology and structure in liver and biliary disease. 2nd ed., Edited by R. Eright, G. H. Philadelphia, pp.13-44.
Mojžiš, J., Nicák, A., Guzy, J., Kron,I. and Mirosay, L. 1998. Effect of stobadine on carbon tetrachloride-induced erythrocyte membrane changes in rats. Free Radi. Bio. & Med. 24: 1374-1351.
Møller, P., Wallin, H. and Knudsen, L. E. 1996. Oxidative stress associated with exercise, psychological stress and life-style factors. Chem. Biol. Interact. 102: 17-36.
Morel, Y. and Barouki, R. 1999. Repression of gene expression by oxidative stress. Biochem. J. 342 Pt 3: 481-496.
Morrissey, P. A. and O’Brien, N. M. 1998. Dietary antioxidants in health and disease. Int. Dairy J. 8: 463-472.
Moskovitz, J., Yim, M. B. and Chock, P. B. 2002. Free radicals and disease. Arch. Biochem. Biophys. 397(2): 354-359.
Mourelle, M. and Franco, M. T. 1991. Erythricyte defects precede the onset of CCl4- induced liver cirrhosis. Protection by silymarin. Life Sci. 48(11): 1083-1090.
Nakamura, T., Nakazawa, Y., Onizuka, S., Satoh, S., Chiba, A., Sekihashi, K., Miura, A., Yasugahira, N. and Sasaki, Y.F. 1997. Antimutagenicity of Tochu tea (an aqueous extract of Eucommia ulnmoides leaves): 1. The clastogen-suppressing effects of Tochu tea in CHO cells and mice. Mutat Res. 388:7-20.
Nakazawa, Y. 1997. Functional and healthy properties of Du-zhoung tea and their utilization. Food industry (in Japamese) 40:6-15
Niki, E. 1991. Action of ascorbic acid as a scavenger of active and stable oxygen radicals. Ame. J. of Clin. Nutr. 54 (6): 1119-1124.
Nishida, K., Ohta, Y. and Ishiguro, I. 1998. Preventive effect of -glutamylcysteinylethyl ester on carbon tetrachloride-induced hepatic triglyceride accumulation in mice. Toxicol. Lett. 95:141-146.
Olson, J.A. 1996. Benefits and liabilities of vitamin A and carotenoids. J Nutr. 126: 1208s-1212s.
Parke, D. V. and Ioannides, C. 1994. The effects of nutrition on chemical toxicity. Drug. Metab. Rev. 26: 739-765.
Poon, M. K. T., Chiu, P. Y., Mark, D. H. F. and Ko, K. M. 2003. Metformin protects against carbon tetrachloride hepatotoxicity in mice. J. Pharmacol. Sci. 93: 1-3.
Pryor, W. A. 1994. Free radicals and lipid peroxidation: what they are and how they got they way. In: Frei, B., eds. Nature Antioxidants in Human Hearth and Disease. Academic Press: San Diego, CA. 1994:1-24.
Quaglia, M. G., Bossu, E., Donati, E., Mazzati, G. and Brandt, A. 1999. Determination of high performance liquid chromatography and capillary electrophoresis. Pharma. and Biomed. Analy. 19: 435-442.
Rajesh, M.G. and Latha, M.S. 2004. Preliminary evaluation of the antihepatotoxic activity of Kamilari, a polyherbal formulaton. J. Ethnopharmacol. 91:99-104.
Ramkumar, K.M., Rajesh, R. and Anuradha, C.V. 2003. Food restriction attenuates blood lipid peroxidation in carbon tetrachloride -intoxicated rats. Nutrition. 19:358-362.
Recknagel, R. O. and Glende, E. A. 1973. Carbon tetrachloride hepatotoxicity: An example of lethal cleavage. CRC Crit. Rev. Toxicol. 2: 263-297.
Rehermann, B. 2003. Immune responses in hepatitis B virus infection. Semin Liver Dis. 23(1): 21-38.
Richard, S. S. 1999. Clinical anatomy for medical study. Lippincott Williams & Wilkins. p.212-219.
Rikans, L. E. and Hornbrook, K. R. 1997. Lipid peroxidation, antioxidant protection and aging. Biochem. Biophys. Acta. 1362: 116-127.
Sachan, D. S. and Dodson, W. L. 1992. Effects of L-carnitine on carbon tetrachloride-induced changes in serum and liver lipids and acylcarnitines. J. Environ. Pathol. Toxicol. Oncol. 11 (3): 125-129.
Sastre, J., Pallardo, F.V., Pla, R., Pellin, A., Juan, G., O''Connor, J.E., Estrela, J.M., Miquel, J. and Vina, J. 1996. Aging of the liver: age-associated mitochondrial damage in intact hepatocytes. Hepatol. 24: 1199-1205.
Schafer, T., Scheuer, C., Roemer, K., Menger, M. D. and Vollmar, B. 2003. Inhibition of p53 protects liver tissue against endotoxin-induced apoptotic and necrotic cell death. FASEB. J. 17(6): 660-667.
Schöneich, C. 1999. Reactive oxygen species and biological aging: A mechanistic approach. Exp. Gerontol. 34: 19-34.
Schuppan, D., Dong, J., Brinkhaus, B. and Hahn, E. G. 1999. Herbal products for liver diseases: a therapeutic challenge for the new millennium. Hepatol. 30: 1099-1104.
Shenoy, K. A., Somayaji, S. N. and Bairy, K. L. 2001. Hepatoprotective effect of Ginkgo Biloba against carbon tetrachloride induced hepatic injury in rats. Indian J. Pharmacol. 33: 260-266.
Skrzydlewska, E., Roszkowska, A., Makiela, M. and Skrzydlewski, Z. 2001. The influence of green tea on the activity of proteases and their inhibitors in plasma of rats after ethanol treatment. Rocz. Akad. Med. Bialymst. 46: 240-250.
Sokal, E. M., Collette, E. and Buts, J. P. 1991. Persistence of a liver metabolic zonation in extra-hepatic biliary atresia cirrhotic livers. Pediatr. Res. 30(3): 286-289.
Sturgill, M. G. and Lambert, G. H. 1997. Xenobiotic-induced hepatotoxity: mechanism of liver injury and methods of monitoring hepatic function. Clin. Chem. 43:1512-1526.
Sugiyama, K., He, P., Wada, S. and Saeki, S. 1999. Teas and other beverages suppress D-galactosamine-induced liver injury in rats. J. Nutr. 129:1361-1367.
Sun, F., Hamagawa, E., Tsutsui, C., Ono, Y., Ogiri, Y. and Kojo, S. 2001. Evaluation of oxidative stress during apoptosis and necrosis caused by carbon tetrachloride in rat liver. Biochi. et Biophy. Acta. 1535: 186-191.
Sundari, P.N., Wilfred, G and Ramakrishna, B. 1997.Dose oxidative protein damage play a role in the pathogenesis of carbon tetrachloride-induced liver injury in the rat ? Biochim. Biophys. Acta. 1362: 169-176.
Thabrew, M. I., Hughes, R. D. and McFarlane, I. G. 1997. Screening of hepatoprotective plant components using a HepG2 cell cytotoxicity assay. J. Pharm. Pharmacol. 49 (11): 1132-1135.
Trimenstein, M. A., Ge, J., Elkins, C. R. and Fariss, M. W. 1999. Administration of the tris salt of alpha- tocopherol hemisuccinate inactivates CYP2E1, enhances microsomal alpha-tocopherol levels and protects against carbon tetrachloride-induced hepatotocixity. Free Radic. Bio. Med. 26(7-8): 825-835.
Tsai, C. H., Miller, A., Spalding, M. and Rodermel, S. 1997. Source strength regulates an early phase transition of tobacco shoot morphogenesis. Plant. Physiol. 115(3): 907-914.
Velmurugan, B., Bhuvaneswari, V., Balasenthil, S. and Nagini, S. 2001. Lycopene, an antioxidant carotenoid modulates glutathione-dependent hepatic biotransformation enzymes during experimental gastric carcinogenesis. Nutri. Res. 21: 1117-1124.
Weber, L. W. D., Boll, M. and Stampfl, A. 2003. Hepatotoxicity and mechanism of action of haloalkanes: carbon tetrachloride as a toxicological model. Crit. Rev. Toxicol. 33(2):105—136.
Wisse, E. 1970. An electron microscopic study of the fenestrated dothelial lining of rat liver sinusoid. J. Ultrastruct. Res. 31:125-150.
Wogan, C. N. 1976. The induction of liver cell cancer by chemicals. In: Liver Cell Cancer. Eds. H. M. Cameron, D. A. Linsell, and G. P. Warsick. Amstredam: Elsevier.
Wong, S.M., Wong, M.M., Seligmann, O. and Wagner, H. 1989. New antihepatotoxic naphtha-pyrone glycosides from the seeds of Cassia tora. Plana Med. 55(3): 276-280.
Wu, C.H., Hsueh, C.L., Song, T.Z. and Yen, G.C. 2001. Inhibitory effects of Cassia tora L. on Benzo [] pyrene-mediated DNA damage toward HepG2 cells. J. Agric. Food Chem. 49: 2579-2586.
Xiao, J., Lu, R., Shen, X. and Wu, M. 2002. Green tea extracts protected against carbon tetrachloride-induced chronic liver damage and cirrhosis. Zhonghua Yu Fang Yi Xue Za Zhi. 36(4): 243-246.
Yang, J., Kato, K., Noguchi. K., Dairaku, N., Koke, T., Iijima,. K., Sekin, H., Ohara S., Sasano,H., Tece. and Shimacc, T. 2003. Tochu (Eucommia ulmoides) leaf extract prevents ammonia and vitamin C deficiency induced gastric mucosal injury. Life Sci. 73:3245-3215.
Yen G.C. and Hsieh C.H. 2002. Inhibitory effects of Du-Zhong (Eucommia ulmoides Oliv.) against low density lipoprotein oxidative modification. Food Chem. 77:449-456.
Yen, G.C. and Hsieh, C.L. 2003. Inhibitory effect of Eucommia ulmoides Oliv. on oxidative DNA damage in lymphocytes induced by H2O2. Tetragogenesis, Carcinogenesis, Mutagenesis. 23: 23-33.
Yen, G.C. and Chen, H.Y. 1995. Antioxidant activity of various tea extracts in relation to their antimutagenicity. J. Agric. Food Chem. 43: 27-32.
Yen, G.C. and Chuang, D.Y. 1999. Antioxidant effects of extracts from Cassia tora L. prepared under different degrees of roasting in the oxidative damage to biomolecules. J. Agric. Food Chem. 47: 1326-1332.
Yen, G.C. and Chuang, D.Y. 2000. Antioxidant properties of water extracts from Cassia tora L. in relation to the degree of roasting. J. Agric. Food Chem. 48: 2760-2765.
Yen, G.C. and Hsieh, C.L. 1998. Antioxidant activity of extracts from Du-zhong (Eucommia ulmoides) towards various lipid peroxidation models in vitro. J. Agric. Food. Chem. 46: 3952-3957.
Yen, G.C. and Hsieh, C.L. 2000. Reactive oxygen species scavenging activity of Du-zhong (Eucommia ulmoides Oliv.) and its active compounds. J. Agric. Food. Chem. 48:3431-3436.
Yen, G.C. and Hsieh, C.L. 2002. Inhibitory effect of Du-zhong (Eucommia ulmoides Oliv.) extracts toward low-density lipoprotein oxidative modification. Food Chem. 77: 449-456.
Yen, G.C., Chen, H.W. and Duh, P.D. 1998. Extraction and identification of an antioxidative component from jui ming zi (Cassia tora L.). J. Agric. Food Chem. 46: 820-824.
Zhang, Q., Yin, J., Zhang, Y. and Zhang, J. 1996a. Quility control of semem Cassiae. Chung Kuo Chung Yao Tsa Chih. 21:646-648.
Zhu, W. and Fung, P. C. W. 2000. The roles played by crucial free radicals like lipid free radicals, nitric oxide, and enzymes NOS and NADPH in CCl4-induced acute liver injury of mice. Free Radical Biol. & Med. 29: 870-880.