中文摘要
在臺灣，民眾罹患肝病盛行率居高不下，而肝病造成之死亡率，多年來亦高居十大死因之前幾位，因此開發有效保護肝臟功能的藥物，一直是生技醫藥產業積極投注資金及研發的重點項目。過去西方醫學對於肝病的治療多採取支持性的保守療法，對於具體促進肝功能的西藥開發進程更是緩慢。從中醫學古籍中草藥相關之記載中，對於保護肝臟的中藥方已有相當清楚的認識，惟肝病中醫藥雖然源遠流長數千年，但由於西方科學盛起之故，未經科學研究證實功效的中醫藥反而屢受質疑。為此，本論文主要研發具保護肝臟功能的傳統中藥，以科學實驗的研究證實相關藥物功效。本研究選用順天堂中藥養肝丸(神立清)顆粒劑探討其抗氧化及肝臟保護的藥效。利用清除DPPH自由基能力測定實驗，本實驗研究結果發現養肝丸(神立清)顆粒劑具備顯著的清除DPPH自由基能力；利用活體外細胞實驗，結果發現養肝丸(神立清)顆粒劑可以緩解因革蘭陰性菌外膜成分脂多糖(LPS)誘發肝臟細胞的損傷。此外，利用動物餵食實驗，結果發現養肝丸(神立清)顆粒劑可以保護小鼠對乙醯胺酚（APAP）誘發的肝毒性。綜觀順天堂中藥養肝丸(神立清)顆粒劑，效能確實並具有抗氧化的功效，再者目前經由科學學理實驗研究證實養肝丸(神立清)顆粒劑確實具有保護肝臟機能功效，因此應該可以作為保肝的中藥。

Abstract
In Taiwan, the prevalence rate of liver disease among the people remains high, and the death rate caused by liver disease has been the highest among the top ten causes of death for many years. Therefore, the development of drugs that effectively protect liver function has always been an active investment and key projects for R&D of the biotechnology and pharmaceutical industry. In the past, Western medicine used supportive conservative treatments for liver disease, and the development of western medicines that specifically promote liver function was slow. From ancient records of Chinese herbal medicines, there is a clear understanding of traditional chinese medicines (TCM) for protecting the liver functions. However, although TCM for liver disease has a long history of thousands of years, due to the rise of Western science, TCM that have not been proven by scientific research, thus TCM have been challenged. In this study, a scientific Chinese medicine of Sun Ten Pharmaceutical Co., Ltd. " Yang Gan Wan (Shen Li Qing) " (YGW) granules were used to study its anti-oxidation and liver protection effects. By using the DPPH free radical scavenging ability measurement experiment, our results found that YGW granules have significant DPPH free radical scavenging ability. By using cell experiments in vitro, our results found that YGW granules could relieve lipopolysaccharide (LPS) -induced damage in liver cells. In addition, by using animal feeding experiments, our results found that YGW granules can protect mice from liver toxicity induced by Acetaminophen (APAP）.To summary the function of YGW granules that have anti-oxidant effects and can indeed protect liver function. We suggested that YGW granules could be an ideal TCM for liver protection.

中文引用：
朱肖鴻、符淑艷、葉蕾(2003)柴胡疏肝散抗肝纖維化治療的療效觀察。
中醫藥學報，31:28-29。
朱文鋒(2007)中醫診斷學。中國中醫藥出版社，北京。
李冀(2014)方劑學。中國中醫藥出版社，北京。
林宗旦、林宗平、林景彬(1996)中藥藥理學。華香園出版社，台北市。
周仲瑛(2009)中醫內科學。中國中醫藥出版社，北京。
俞君平、朱蔚崗、宋鴻范(1997)柴胡疏肝散加減治療病毒性肝炎合併膽道感染65例。實用中西醫結合雜誌，10:865-866。
孫廣仁(2007)中醫基礎理論。中國中醫藥出版社，北京。
高學敏(2008)中藥學。中國中醫藥出版社，北京。
陳奇(1993)中藥名方藥理與應用。南天書局，台北市。
楊曉冰(1997)柴胡疏肝散加味治療慢性乙型肝炎58例療效觀察。交通醫學，11:9。
翟建富(2008)現代文明疾病的因應。科學發展雜誌，422:12-17。
潘志堅、鐘澤鑫(2001)柴胡疏肝散治療酒精性之脂肪肝60例。實用中醫藥雜誌，17:22-23。

英文引用：
Akif D, Ali G, Bilal U, Selcuk I, & Emin TE (2016) Oxidative stress and antioxidant parameters in neutropenic patients secondary to chemotherapy. Pakistan J Medical Sciences, 32(2), 309-313.
Angsutararux P, Luanpitpong S, & Lssaragrisil S (2015) Chemotherapy-induced cardiotoxicity: overview of the roles of oxidative stress. OxiMed &
Cellular Longevity, 1-13. online publication. Doi:10.1155/2015/795602
Bahramsoltani R, Rahimi R, Farzaei MH (2017) Pharmacokinetic interactions of curcuminoids with conventional drugs: A review. J. Ethnopharm, 209, 1–12.
Bernal W, Auzinger G, Dhawan A, Wendon J (2010) Acute liver failure. The Lancet, 376, 190-201.
Bissell DM. (2001) Chronic liver injury, TGF-beta, and cancer. Exp Mol Med, 33(4), 179-190.
Clark, AM (1996) Natural products as a resource for new drugs. Pharm. Res, 13(8), 1133–1141.
Cobb JP, Hotchkiss RS, Karl IE, Buchman TG (1996) Mechanisms of cell injury and death. Br J Anaesth, 77, 3–10.
Cohen SD, Khairallah EA (1997) Selective protein arylation and acetaminophen-induced hepatotoxicity. Drug metab reviews, 29(1&2), 59-77.
Dai G, He L, Chou N, and Y.-J. Y. Wan YJY (2006) Acetaminophen metabolism does not contribute to gender difference in its hepatotoxicity in mouse. Toxicol Sciences, 92(1) 33–41.
Dianelena EP, He AMOS and Jose PC (2016) Role of food-derived antioxidant agents against acetaminophen-induced hepatotoxicity. Pharm Biology, 54(10), 2340–2352.
Dieperink E, Ho SB, Tetrick L, Thuras P, Dua K, Willenbring ML (2004) Suicidal ideation during interferon-alpha2b and ribavirin treatment of patients with chronic hepatitis C. Gen Hosp Psychiatry, 26, 237-240.
Du K, Ramachandran A and Jaeschke H (2016) Oxidative stress during acetaminophen hepatotoxicity: sources, pathophysiological role and therapeutic potential. Redox Biol, 10, 148–156.
Friedman SL (2000) Molecular regulation of hepatic fibrosis, an integrated cellular response to tissue injury. J Biol Chem, 275(4), 2247-2250.
Gebhardt R. (2000) Oxidative stress, plant-derived antioxidants and liver fibrosis. Planta Med, 68(4), 289-296.
Gordaliza, M. (2007) Natural products as leads to anticancer drugs. Clin Transl Oncol, 9, 767–776.
Gyamfi MA, Yonamine M, Aniya Y. (1999) Free radical scavenging activity of medicinal herb of Ghana: Thonningia sanguinea on experimentally induced liver injuries. General Pharmacol, 32, 661-67.
Hammel P, Couvelard A, O'Toole D, Ratouis A, Sauvanet A, Flejou JF, Degott C, Belghiti J, Bernades P, Valla D, Ruszniewski P, Levy P. (2001) Regression of liver fibrosis after biliary drainage in patients with chronic pancreatitis and stenosis of the common bile duct. N Engl J Med, 344(6), 418-423.
Hinson JA, Roberts DW, and James LP (2010) Mechanisms of acetaminophen-induced liver necrosis. Handb Exp Pharmacol, 196, 369–405.
Houten BV, Gloria A. Santa-Gonzalez, and Mauricio Camargo M (2018) DNA repair after oxidative stress: current challenges. Published in final edited form as: Curr Opin Toxicol, 7, 9–16.
Ho CM, Lee CH, Wang JY, Lee PH, Lai HS and Hu PH (2014) Nationwide Longitudinal Analysis of Acute Liver Failure in Taiwan. Medicine. 93(4), 1-9.
Huang YT, Lee TY, Lin HC, Chou TY, Yang YY, Hong C-Y (2001) Hemodynamic effects of Salvia miltiorrhiza on cirrhotic rats. Can J Physiol Pharmacol, 79(7), 566-572.
Huang XJ, Yang KC, Im YK, Yarimaga HS, Yoon O, E. and Kim HS (2006) Aspartate Aminotransferase (AST/GOT) and Alanine Aminotransferase (ALT/GPT) Detection Techniques. Review. Sensors, 6(7), 756-782.
Iredale JP (2001) Hepatic stellate cell behavior during resolution of liver injury. Semin Liver Dis, 21(3), 427-436.
James LP, Mayeux PR and J. A. Hinson JA (2003) “Acetaminophen- induced hepatotoxicity,” Drug Metabolism and Disposition. The Biological Fate of Chemicals, 31(12), 1499– 1506.
Mitchell JR, Thorgeirsson SS, Potter WZ, Jollow DJ, and Keiser H (1974) Acetaminophen-induced hepatic injury: protective role of glutathione in man and rationale for therapy. Clinical Pharmacology and Therapeutics, 16(4), 676–684.
Krystona TB, Georgieva AB, Pissis P, Alexandros G, Georgakilas AG (2011) Role of oxidative stress and DNA damage in human carcinogenesis. Mutation Research 711(1-2), 193–201.
Kuttan R, Bhanumathy P, Nirmala K, George M. (1985) Potential anticancer activity of turmeric (Curcuma longa). Cancer Lett, 29(2), 197–202.
Lee WM (2003) Drug-induced hepatotoxicity. N Engl J Med, 349, 474-485.
Li C, Luo J, Li L, Cheng M, Huang N, Liu J, Waalkes MP (2003) The collagenolytic effects of the traditional Chinese medicine preparation, Han-Dan-Gan-Le, contribute to reversal of chemical-induced liver fibrosis in rats. Life Sci, 72, 1563-1571.
Maheshwari RK,Singh A.K, Gaddipati J, Srimal RC (2006) Multiple biological activities of curcumin: A short review. Life Sci, 78(18), 2081–2087.
Matsuda Y, Matsumoto K, Yamada A, Ichida T, Asakura H, Komoiya Y, Nishiyama E, Nakamura T. (1997) Preventive and Therapeutic effects in rat of Hepatocyte growth factor infusion on liver fibrosis/cirrhosis. Hepatology, 26(1) 81-89.
Mohammad HF, Zobeiri M, Parvizi F, Fardous F. El-Senduny, Ilias Marmouzi, Coy-Barrera E, Rozita Naseri R, Nabavi SM, Rahimi R and Abdollahi M (2018) Curcumin in Liver Diseases: A Systematic Review of the Cellular Mechanisms of Oxidative Stress and Clinical Perspective. Nutrients, 10(7), 1-28.
Muller FL, Lustgarten MS, Jang Y, Richardson A, & Van Remmen H (2007) Trends in oxidative aging theories. Free Radical Biology & Medicine, 43(4), 477-503.
Nakamura T, Sakata R, Ueno T, Sata M, Ueno H. (2000) Inhibition of tansforming growth factor β prevents progression of liver fibrosis and enhance hepatocyte regeneration in dimethylnitrosamine-treated rats. Hepatology, 32, 247-255.
Prati D, Taioli E, Zanella A, Della Torre E, Butelli S, Del Vecchio E, Vianello L, Zanuso F, Mozzi F, Milani S, Conte D, Colombo M, Sirchia G (2002) Updated definitions of healthy ranges for serum alanine aminotransferase levels. Ann Intern Med, 137(1), 1-10.
Rojkind M, Greenwel P. Pathophysiology of liver fibrosis. In: Arias IM, Boyer JL, Chisari FV, Fausto N, Schachter D, and Shafritz DA (2001) The Liver: Biology and Pathobiology. 4th ed. Philadelphia: Lippincott Williams & Wilkins. 721-738.
Sakaida I, Matsumura Y, Akiyama S, Hayashi K, Ishige A, Okita K (1998) Herbal medicine Sho-saiko-to (TJ-9) prevents liver fibrosis and enzyme-altered lesions in rat liver cirrhosis induced by a choline-deficient L-amino acid-deficient diet. J Hepatol, 28(2), 298-306.
Satoskar R, Shah S, Shenoy S (1986) Evaluation of anti-inflammatory property of curcumin (diferuloyl methane) in patients with postoperative inflammation. Int. J. Clin. Pharmacol. Ther. Toxicol, 24(12), 651–654.
Schuppan D, Porov Y. (2002) Hepatic fibrosis: from bench to bedside. J Gastroenterol Hepatol, 17, S300-S305.
Shimizu I, Ma YR, Mizobuchi Y, Liu F, Miura T, Nakai Y, Yasuda M, Shiba M, Horie T, Amagaya S, Kawada N, Hori H, Ito S. (1999) Effects of Sho-saiko-to, a Japanese herbal medicine, on hepatic fibrosis in rats. Hepatology, 29(1) 49-160.
Shiratori Y, Imazeki F, Moriyama M, Yano M, Arakawa Y, Yokosuka O, Kuroki T, Nishiguchi S, Sata M, Yamada G, Fujiyama S, Yoshida H, Omata M (2000) Histologic improvement of fibrosis in patients with hepatitis C who have sustained response to interferon therapy. Ann Intern Med, 132(7), 517-524.
Sharma O (1976) Antioxidant activity of curcumin and related compounds. Biochem. Pharmacol, 25(15), 1811–1812.
Sidhu GS, Singh AK, Thaloor D, Banaudha KK, Patnaik GK, Srimal RC, Maheshwari RK (1998) Enhancement of wound healing by curcumin in animals. Wound Repair Regen, 6(2) 167–177.
Singh D, Cho, WC and Upadhyay G (2016) Drug-induced liver toxicity and prevention by herbal antioxidants: an overview. Front physiol, 6, 1-18.
Smilkstein MJ, Knapp GL, Kulig KW (1988) Efficacy of oral N-acetylcysteine in the treatment of acetaminophen overdose. N Engl J Med, 319(24), 1557-1562.
Sterba M, Popelova O, Vavrova A, Jirkovsky E, Kovarikova P, Gersl V, & Simunek T (2013) Oxidative stress, redox signaling, and metal chelation in anthracycline cardiotoxicity and pharmacological cardioprotection. Antioxid Redox Signal, 18(8), 899-929.
Stickel F, Brinkhaus B, krahmer N, Seitz HK, Hahn EG, Schuppan D. (2002) Antifibrotic properties of botanicals in chronic liver disease. Hepatogastroenterology, 49, 1102-1108.
Srimal R, Dhawan B (1973) Pharmacology of diferuloyl methane (curcumin), a non-steroidal anti-inflammatory agent. J Pharm Pharmacol, 25(6), 447-52.
Su SY and Lee WC (2019) Mortality trends of liver diseases from 1981 to 2016 and the projection to 2035 in Taiwan: An age‐period‐cohort analysis . Liver International, 39(4), 770–776.
Wang k, Peng CP, Wang H, Tang Z, Wang N, Wang J. & Zhang Y (2016) Chronic administration of Angelica sinensis polysaccharide effectively improves fatty liver and glucose homeostasis in high-fat diet-fed mice. Scientific Reports, 6, 26229, 1-11.
Wasser S, Ho JMS, Ang HK, Tan CEL (1998) Salvia miltiorrhiza reduced experimentally induced hepatic fibrosis in rats. J Hepatol, 29(5), 760-771.
Woreta TA, Alqahtani, SA (2014) Evaluation of Abnormal Liver Tests. Med Clin N Am, 98(1), 1–16.
Kang W, Robitaille MC, Merrill M, Kim T, C.W. & Raphael MP (2020) Mechanisms of cell damage due to mechanical impact: an in vitro investigation. Scientific Reports, 10, 12009, 1-12.
Woolbright BL and Jaeschke H (2017) Role of the inflammasome in acetaminophen-induced liver injury and acute liver failure. J Hepatology, 66(4), 836–848.
Wu PS , Wu SJ, Tsai YH, Lin YH, Chao JCJ (2011) Hot water extracted Lycium barbarum and Rehmannia glutinosa inhibit liver inflammation and fibrosis in rats. Am J Chin Med. 39(6), 1173-91.
Xiao J, So KF, Liong EC, Tipoe GL (2013) Recent advances in the herbal treatment of non-alcoholic Fatty liver disease. J. Tradit. Complement. Med, 3(2), 88–94.
Zhang A, Sun, H, Wang X (2013) Recent advances in natural products from plants for treatment of liver diseases. Eur J Med Chem, 63, 570–577.
Zhang J, Lei W, Chen X, Wang S & Qian W (2018) Oxidative stress response induced by chemotherapy in leukemia treatment (review). Molecular and Clinical Oncologyy, 8(3) 391-399.