中藥炮製之目的是藉由中藥材的加工過程，來提升中草藥的療效及降低藥物之毒性。刺五加Acanthopanax senticosus（Rupr. Et Maxim）Harm.根及莖，為五加科（Araliaceae）植物。在本實驗中，將刺五加分別以酒炙、醋炙及醱酵三種方法進行炮製，酒炙及醋炙以現代科技控溫、定時高溫壓方式進行炮製，提升炮製的效率及幼纂C利用刺五加中藥材進行紅麴菌製麴醱酵生成刺五加紅麴，分析有效成份Monacolin K及代謝產物Citrinin含量變化。將經過炮製之酒炙刺五加、醋炙刺五加及刺五加紅麴以高效液相層析法進行炮製前後成份分析，瞭解指標成份含量變化，並分析製麴後是否生成Monacolin K及Citrinin，將刺五加及其炮製品以乙醇萃取並進行抗氧化試驗、急性毒性試驗、降血脂試驗及評估肝中超氧化物岐化酶（superoxide dismutase）之活性。
結果顯示以現代科技高溫壓方式進行炮製之刺五加其炮製效果有優於傳統炮製，能進一步運用在製藥產業上來提升炮製效率及幼纂C在七種紅麴菌種中以紅麴菌 BCRC 3161 菌株所醱酵之刺五加紅麴有較高的Monacolin K產率（53.51±1.66μg/g）。刺五加及其炮製品在急性毒性試驗中並無小鼠死亡，顯示炮製品並無急性毒性。藥理實驗中，在清除DPPH自由基能力以高溫壓醋炙刺五加效果最佳（82.25±0.63%）。在四周降血脂評估實驗中，以高溫壓醋炙刺五加及刺五加紅麴效果最佳，其總膽固醇下降率分別為27.3±1.53%及29.9±1.38%。刺五加及其炮製品在肝中超氧化物岐化酶之活性評估中，以高溫壓醋炙刺五加37.47±0.86%為最佳。高溫壓醋炙刺五加其清除DPPH自由基能力、降血脂能力及超氧化物岐化酶活性皆有優於未炮製刺五加，刺五加在經紅麴製麴後生成Monacolin K，顯示刺五加在經過現代化炮製方式後的確能增強作用，希望這些結果可以提供藥廠在炮製技術的選擇並增進產業界發展保健食品或藥品之規範。

In this study, we propose to use traditional Chinese medicine (TCM) crude drugs, Ciwujia (Acanthopanax senticosus (Rupr. Et Maxim) Harm) that it changes their pharmaceutical properties after steam concocting. Ciwujia is a subject plant of Araliaceae, the medical position takes dry tuberous root. This experiment, in order to use the dry ripe tuberous root of Ciwujia. Ciwujia with multiple potencies need to pass proper treatments in order to reach the anticipated result are well known facts. Furthermore, the Ciwujia ingredients with irritating and toxic effect may produce the side effects and poison in clinic without proper pretreatment In the present study, the concocted of Ciwujia would be analyzed by high pressure liquid chromatography assay and to evaluate pharmacological activities. The extract of processed Ciwujia isolated from ethanol was employed to evaluate antioxide activities, lipid lowering effects and superoxide dismutase activity.
Ciwujia was fermented by Monascus purpureus BCRC 31615 which had a higher production of monacolin K (53.51±1.66μg/g). In acute toxic test, the result shows that the little experimental mouses are no death. It is showed that Ciwujia and its process product is not obvious acute toxicity. In clean DPPH free radical text, Ciwujia is incubated with vinegar and processed by high-temperature and high-pressure method that have high ability to scavenge the radicals (82.25±0.63%). In lipid lowering effects test, Ciwujia with red yeast and Ciwujia is incubated with vinegar and processed by high-temperature high-pressure method that have higher lower cholesterol effect (27.3±1.53% and 29.9±1.38%). In superoxide dismutase activity test, Ciwujia is incubated with vinegar and processed by high-temperature and high-pressure method that have higher superoxide dismutase activity (37.47±0.86%). The results will provide valuable information for both academic and industrial parties.

誌謝……………………………………………………………………Ⅰ
摘要……………………………………………………………………Ⅱ
ABSTRACT……………………………………………………………Ⅲ
目錄……………………………………………………………………Ⅳ
表目次…………………………………………………………………Ⅵ
圖目次………………………………………………………………Ⅶ
第一章 前言……………………………………………………………1
第二章 總論……………………………………………………………3
第一節 刺五加文獻回顧…………………………………………….3
（一） 刺五加簡介…………………………………………………3
（二） 刺五加主要化學成分………………………………………5
（三） 刺五加與適應原……………………………………………6
（四） 刺五加藥理作用……………………………………………6
第二節 中藥炮製簡介…………………………..……………………9
（一）中藥炮製目的…………………………………..…………..9
（二）酒炙法簡介………………………………………………..10
（三）醋炙法簡介………………………………………………..11
（四）蒸製炮製法介紹…………………………………………..13
（五）發酵法簡介………………………………………………..14
第三節 紅麴菌效用與研究…………………………………………16
（一）紅麴代謝產物………………………..……………………16
（二）紅麴在食品上的運用……………………………………..17
第四節 高血脂症……………………………………………………18
（一） 血漿脂蛋白生理…………………………………………..18
（二） 血清脂蛋白濃度之評估…………………………………..19
（三） 高三酸甘酯血症及高膽固醇血症的治療……………..…20
（四） 脂肪與心血管疾病………………………………………..23
第三章 材料與方法…………………………………………………..25
第一節 實驗材料……………..……………………………………25
（一） 實驗動物…………………………………………………..25
（二） 儀器設備…………………………………………………..25
（三） 試劑與藥品………………………………………………..26
（四） 誘導高血脂飼料配方組成………………………………..27
第二節 實驗方法……………………………………………………27
（一）基原鑑定……………………………………………………29
（二）刺五加炮製方法……………………………………………31
（三）炮製前後成分分析…………………………………………35
（四）體外清除DPPH自由基效力測定…………………………38
（五）炮製前後毒理及藥理試驗…………………………………39
（六）血清生化學的檢測…………………………………………40
第三節 統計方式……………………………………………………41
第四章 結果……………….………………………………………….42
第一節 基原鑑定………….…..…………………………………….42
（一）刺五加外觀………….…………………………………….42
（二）刺五加組織切片………….……………………………….42
（三）刺五加薄層層析鑑定………….………………………….42
（四）刺五加高效液相層析鑑定………….…………………….42
第二節 刺五加炮製前後成分分析………………………….……...42
（一）薄層層析鑑定………………………………….….……....42
（二）高效液相層析法鑑定………………………….…….…....43
第三節 體外清除DPPH自由基效力測定………………………….44
（一）酒炙刺五加體外清除DPPH自由基效力測定……….….44
（二）醋炙刺五加體外清除DPPH自由基效力測定……….….44
（三）刺五加紅麴體外清除DPPH自由基效力測定…………..44
第四節 炮製前後毒理評估及藥理活性篩選………………………46
（ㄧ）急性毒性試驗……………………………………………..45
（二）血清中三酸甘油酯（triacylglycerols）、膽固醇（cholesterol）變化………………………………………..………………45
（三）刺五加及其炮製品之超氧岐化酶活性評估……………..45
第五章 討論…………………………………………………………..47
第六章 結論…………………………………………………………..

丁予安等 (1997) 高血脂防治手冊:國人血脂異常診療及預防指引，行政院衛生署。
王志傑 (2003) 紅麴菌二級代謝產物之生產與應用研究，台灣大學微生物與生物化學研究所博士論文。
王筠默 (1985) 中藥藥理與臨床，綜合出版社。
中國藥典委員會編 (2005) 中國藥典，化學工應出版社。
中國醫藥委員會 (1991)中國藥典中藥彩色圖集，旺文社。
史久良、高奎憲 (1987) 近五年來我國刺五加研究和發展概況簡介，黑龍江省中醫研究院出版。
左中丕 (2002) 中藥鑑別炮製應用手冊，軍事醫學科。
行政院衛生署中醫藥委員會 (2002) 中藥對照用指標成份，物理化學資料彙編。
行政院衛生署 (2000) 易混淆及誤用藥材之鑑別(Ⅰ)，行政院衛生署藥物食品檢驗局。
旭丘光 (1996) 七種神奇的機能性食品，世茂出版社。
李家實 (2000) 中藥鑑定學，上海科技技術出版社。
杭群 (1998) 刺五加的神奇療效，世茂出版社。
林宗平、林宗旦 (1996) 中藥藥理學，華香園出版社。
林讚峰 (1992) 紅麴菌研究發展之演進，科學農業 40:193-198。
林讚峰 (1994) 紅麴菌的特性及應用，生物產業 5:29-35。
林讚峰 (1995) 紅麴菌培養工藝及紅麴運用之演進，製酒科技專論編會 17:156-168。
金世元、王琦 (2004) 中藥飲片炮製研究與臨床應用，化學工業出版社。
高木釗 (1981) 新編中藥大辭典，新文豐出版公司。
國家中醫藥管理局編 (1999) 中華本草，上海科學技術出版社。
陳德昌 (1996) 現代實用本草，人民衛生出版社。
陳彥霖、李昭蓉、陳建州、袁國芳 (1998) 紅麴菌種的開發與應用，食品工業月刊 30:1-9。
張貴君 (2002) 臨床中藥應用鑑別圖譜，人民衛生出版社。
張賢哲，蔡貴花 (2003) 中藥炮製學，中國醫藥學院印行。
張賢哲 (2007) 道地藥材圖鑑，中國醫藥大學印行。
常新全、丁雨霞 (2002) 中藥活性成分分析手冊，學苑出版社。
黑龍江省祖國醫藥研究所編 (1981) 中國刺五加研究，黑龍江科學技術出版社。
葉定江 (2001) 中藥炮製學，知音出版社。
雷國蓮 (2002) 中藥炮製技術指南，世界圖書出版公司。
楊明道等編譯 (2002) Cecil基礎內科學，合記圖書出版社。
趙一、黃國鈞 (1989) 實用補養中藥，中國廣西科學技術出版社。
鄭虎占 (1997) 中藥現代研究與應用，學苑出版社。
謝萬宗 (2004) 實用中藥材經驗鑑別，知音出版社。
蘇遠志 (2001a) 奇妙的紅麴，元氣齋出版社。
蘇遠志 (2001b) 紅麴製品介紹及國內研究現況，機能性醱酵製品研討會 p.67-112。
龔千鋒 (2002) 中藥炮製學，中國中醫藥出版社。
Agren JJ, Hallikainen M, Vidgren H, Miettinen TA, Gylling H. (2006) Postprandial lipemic response and lipoprotein composition in subjects with low or high cholesterol absorption efficiency. Clinica Chimica Acta; International Journal of Clinical Chemistry. 366:309-315.
Alastair JJ, Rpbert HK. (1999) Drug treatment of lipid disorder. The New England Journal of Medicine. 341:498-511.
Albert AW, Chen J, Spring J. (1980) Mevinolin: a highlypotent competitive inhibitor of hydroxylmethylglutaryl-coenzyme A reducetase and a cholesterol lowing agent. Proceedings of the National Academy of Sciences of the United States of America. 77:3957-3961.
Anderson KM, Castelli WP, Levy D. (1987) Cholesterol and mortality: 30 years of follow-up from the Framingham Study. The Journal of the American Medical Association. 257:2176 -2180.
Aniya Y, Ohtani II, Higa T, Miyagi C, Gibo H, Shimabukuro M, nakanish H, Taira J, (2000) Dimerumic acid as an antioxidant of the mold: Monascus anka. Free Radical Biology & Medicine. 28:999-1004.
Aniya Y, Yokomakura Y, Yonamine M, Shimada K, Nagamine T, Shimabukuro M, Gibo H. (1999) Screening of antioxidant action of various molds and protection of Monascus anka against experimentally induced liver injuries of rats. General Pharmacology. 32:225-231.
Asano K, Takahashi T, Miyashita M, Matsuzaka A, Muramatsu S, Kuboyama M, Kugo H, Imai J. (1986) Effect of Eleutherococcus senticosus extract on human physical working capacity. Planta Medica. 3:175-177.
Bezdetko GN, Dardymov IV, Speranskaya NY, (1980) Effect of ginseng and eleutherococcus on the constent of cyclic-nucleotides. Farmakologia Toksikologia. 43:448-455.
Blance PJ, Loret MO, Santerre AL, Pareilleux A, Prome D, Prome JC, Laussac JP, Goma G. (1994) Pigment of Monascus. Journal of Food Science. 59:862-865.
Bohn B, Nebe CT, Birr C. (1987) Flow-cytometric studies with Eleutherococcus senticosus extract as an immunomodulatory agent. Arzneimittel Forschung. 37:1193-1196.
Boon H, Smith M. (1999) The Botanical Pharmacy. Kingston, Ontario: Quarry Press; 194.
Brown G, Albers JJ, Fisher LD, (1990) Regression of coronary artery
disease as a result of intensive lipid-lowering therapy in men with
high levels of apolipoprotein B. The New England Journal of Medicine. 323:1289-1298.
Bu Y, Jin ZH, Park SY, Baek S, Rho S, Ha N, Park SK, Kim H, Sun Y K. (2005) Siberian ginseng reduces infarct volume in transient focal cerebral ischaemia in Sprague-Dawley rats. Phytotherapy Research. 19:167-169.
Byington RP, Jukema JW, Salonen JT. (1995) Reduction in
cardiovascular events during pravastatin therapy: pooled analysis of clinical events of the Pravastatin Atherosclerosis Intervention
Program. Circulation. 92:2419-2425.
Carlson LA, Rosenhamer G. (1988) Reduction of mortality in the Stockholm Ischaemic Heart Disease Secondary Prevention Study by Combined treatment with clofibrate and nicotinic acid. Acta Medica Scandinavica. 223:405-418.
Daniel SP, Thomas EC, John CK, Joseph LW. (1989) Beyond cholesterol modifications of Low-Density Lipoprotein That Increase it’s Atherogenicity. The New England Journal of Medicine. 320: 915-924.
Dardymov IV, Khasina EI, Bezdetko GN. (1978) Insulinlike action of eleutherosides from the roots of Eleutherococcus senticosus. Rastit Resur. 14:86-89.
Davydov M, Krikorian AD. (2000) Eleutherococcus senticosus (Rupr. & Maxim.)Maxim. (Araliaceae) as an adaptogen a closer look. Journal of Ethnopharmacology. 72:345-349.
De LM, Salen P, Martin JL. (1999) Mediterranean diet, traditional risk actors, and the rate cardiovascular complications after myocardial infarction: final report of the Lyon Diet Heart Study.Circulation. 8:843-864.
Denke MA. (1995) Cholesterol-lowering diets; a review of the evidence. Archives of Iinternal Medicine. 155:17-26
Deyama T, Nishibe S, Nakazawa Y. (2001) Constituents and pharmacological effects of Eucommia and Siberian ginseng. Acta Pharmacologica Sinica. 22:1057-1070.
Diane KW, Dianne LK, Thomas PG. (1988)Prescribed use of cholersterol lowering drugs in the United States. The Journal of the American Medical Association.. 263:2185-2188.
Facchinetti F, Neri I, Tarabusi M. (2002) Eleutherococcus senticosus reduces cardiovascular response in healthy subjects: a randomized, placebo-controlled trial. Stress Health. 18:11-17.
Frick MH, Elo O, Hapa K. (1987) Helsinki heart study: Primary preventiontrial with gemfibrozil in middle-aged men with dyslipidemia. Safetyof treatment changes in risk of factors, and incidence of coronaryheart disease. The New England Journal of Medicine. 317:1237-1245.
Fujikawa T, Kanada N, Shimada A, Ogata M, Suzuki I, Hayashi I, Nakashima K. (2005) Effect of sesamin in Acanthopanax senticosus HARMS on behavioral dysfunction in rotenone-induced parkinsonian rats. Biological & Pharmaceutical Bulletin. 28(1):169-172.
Fujikawa T, Soya H, Hibasami H, Kawashima H, Takeda H, Nishibe S, Nakashima K. (2002) Effect of Acanthopanax senticosus Harms on biogenic monoamine levels in the rat brain. Phytotherapy Research. 16:474–478.
Glatthaar SB, Sacher F, Esperester A. (2001) Antiviral activity of an extract derived from roots of Eleutherococcus senticosus. Antiviral Research. 50:223-228.
Gordon T, Kannel WB, Castelli WP, Dawber TR. (1981) Lipoproteins,
cardiovascular disease, and death: the Freamingham study. Archives of Iinternal Medicine. 141:1128-1131.
Hikino H, Takahashi M, Otake K, Konno C. (1986) Isolation and hypoglycemicactivity of eleutherans A, B, C, D, E, F, and G: Glycans of Eleutherococcus senticosus roots. Journal of Natural Products. 49: 293-297.
Illingworth DR, Tobert JA. (1994) A review of clinical trials comparing
HMG-CoA reductase inhibitors. Clinical Therapeutics. 16:366-385.
Jiang W, Li W, Han L, Liu L, Zhang Q, Zhang S, Nikaido T, Koike K. (2006) Biologically active triterpenoid saponins from Acanthopanax senticosus. Journal of Natura Products. 69:1577-1581
Joseph PF, Stephen JZ, Jonathan MS. (1998) Physician noncompliance
with the 1993 national cholesterol education program ( NCEP-ATPⅡ) guidelines. Circulation. 98:851-855.
Kimura Y, Sumiyoshi M. (2004) Effects of various Eleutherococcus senticosus cortex on swimming time, natural killer activity and corticosterone level in forced swimming stressed mice. Journal of Ethnopharmacology. 95:447-453.
Knopp RH, Ginsberg J, Albers JJ. (1985) Contrasting effects of unmodified and time-release forms of niacin on lipoproteins in
hyperlipidemic subjects: clues to mechanism of action of niacin.
Metabolism. 34:642-650.
Lee S, Son D, Ryu J, Lee YS, Jung SH, Kang J, Lee SY, Kim HS, Shin KH. (2004) Anti-oxidant activities of Acanthopanax senticosus stems and their lignan components. Archives of Pharmacal Research. 27:106-110.
Lin CC, Huang PC. (2000) Antioxidant and hepatoprotective effects of Acathopanax senticosus. Phytotherapy Research. 14:489- 494.
Mcpherson R, Tsoukas C, Baines MG. (1993) Effects of lovastatin on natural killer cell function and other immunological parameters in
man. Journal of Clinical Immunology. 13:439-444.
Moghadasian MH, Mcmanus BM, Godin DV, Rodrigues B, Frohlic
JJ. (1999) Proatherogenic and antiatherogenic effects of probucol
phytosterols in apoliprotein E-deficient mice. Circulation. 99: 1733 -1739.
Monograph. (2006) Eleutherococcus senticosus. Alternative Medicine Review 11:819-838.
National Cholesterol Education Program Expert Panel. (1998) Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of high Blood Cholesterol in Adults. Archives of Internal Medicine. 148:36-69.
Nishibe S, Kinoshita H, Takeda H, Okano G. (1990) Phenolic compounds from stem bark of Acanthopanax senticosus and their pharmacological effect in chronic swimming stressed rats. Chemical & pharmaceutical Bulletin. 38:1763-1765.
Pac-Kozuchowska E. (2007) Evaluation of lipids, lipoproteins and apolipoproteins concentrations in cord blood serum of newborns from rural and urban environments. Annals of Agricultural and Environmental Medicine. 14:25-29.
Panossian A, Wagner H. (2005) Stimulating effect of adaptogens: an overview with particular reference to their efficacy following single dose administration. Phytotherapy Research. 19:819-838.
Park SH, Lee SG, Kang SK, Chung SH. (2006) Acanthopanax senticosus reverses fatty liver disease and hyperglycemia in ob/ob mice. Archives of Pharmacal Research. 29:768-776.
Phuong NT, Lee KA, Jeong SJ, Fu CX, Choi JK, Kim YH, Kang JS. (2006) Capillary electrophoretic method for the determination of diterpenoid isomers in Acanthopanax species. Journal of Pharmaceutical and Biomedical Analysis. 40:56-61.
Regnstrom J, Nilsson J. (1994) Lipid oxidation and inflammation induced intimal fibrosis in Coronary heart disease. Journal of Laboratory & Clinical Medicine. 124:162-168.
Sacks FM, Pfeffer MA, Moye LA. (1996) The effect of pravastatin on
coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and recurrent events trail investigators. The New England Journal of Medicine. 335:1001- 1009.
Srinivasan K, Viswanad B, Asrat L, Kaul CL, Ramarao P. (2005) Combination of high-fat diet-fed and low-dose streptozotocin-treated rat: a model for type 2 diabetes and pharmacological screening. Pharmacological Research. 52:313-320.
Stehbens WE. (1999) The oxidative stree hypothesis of atherosclerosis:
cause or product? Medical Hypotheses. 53: 507-515.
Subrahmanyam V, Mantha, Jawahar Kalra, Kailash Prasad. (1996) Effect of probucol on hypercholesterolemia-induced changes in antioxidant enzymes. Life Sciences. 58: 503-509.
Sui DY, Lu ZZ, Ma LN, Fan ZG. (1994) Effects of the leaves of Acanthopanax senticosus (Rupr. et Maxim.) Harms. on myocardial infarct size in acute ischemic dogs. China Journal of Chinese materia medica. 19:746-764.
Takahiko F, Shinji M, Nariyasu K, Naoya N, Masato O,Ikukatsu S, Kunio N. (2005) Acanthopanax senticosus Harms as a prophylactic for MPTP-induced Parkinson’s disease in rats. Journal of Ethnopharmacology. 97: 375–381.
Tang W, Eisenbrand G. (1992) Chinese Drugs of Plant Origin. Heidelberg, Germany: Springer Verlag; 1.
Vaughan CJ, Murphy MB, Buckley BM. (1996) Statins do more than just lower cholesterol. Lancet. 348:1079-1082.
Watts GF, Lewis B, Brunt JN. (1992) Effects on coronary artery disease of lipid-lowering diet, or diet plus cholestyramine, in the St Thomas'' Atherosclerosis Regression Study (STARS). Lancet. 339:563-569.
Windler E, Schöffauer M, Zyriax BC. (2007) The significance of low HDL-cholesterol levels in an ageing society at increased risk for cardiovascular disease. Diabetes & Vascular Disease Research. 4(2):136-142.
Yu W, Zhang H, Huang W, Chen J, Liang X. (2005) Analysis of the volatile oil from the stem of Acanthopanax senticosus (Rupr. et Maxim.) harms with several hyphenated methods of gas chromatography. Chinese Journal of Chromatography. 23:196-201.