臺灣博碩士論文加值系統

順氯氨鉑（cisplatin， CDDP）是臨床上治療固體癌的常用化學治療藥物，其所引起的腎毒性常是限制臨床使用的主要原因。本研究的目的即在於評估人參及其純成分人參皂苷於CDDP所引起的腎炎之預防效果。
實驗動物為6週齡母鼠（BALB/c mice），經腹腔連續五天給予5 mg/kg 的CDDP以引發腎炎。在給予CDDP前五天開始經口投予小鼠人參濃縮劑（ginseng extract，GE）125, 250, 500 mg/kg/d或人參皂苷（ginsenoside，GS）Rb1、Rd、Rg1 5 mg/kg/d做為預防藥物。實驗結果顯示，給予GE及GS對於N-acetyl-beta-D-glucosaminidase（NAG）、尿中肌酸酐（urine creatinine）、尿蛋白 （urine protein）與血中尿素氮（BUN）皆有不同程度的改善效果；腎組織損傷相較於對照組也有明顯減緩的趨勢。在免疫螢光染色方面，TNF-α的量明顯受到抑制，p21及PCNA的表現亦有不同程度的增加。
因此可以推論，經口投予人參濃縮劑及人參皂苷可以藉由抑制發炎反應、阻止細胞週期的前進並促進DNA修復以達到腎臟保護的效果。

Cisplatin (CDDP) is one of the most commonly used antineoplastic agents for the solid tumor treatment. The major side effect of CDDP is nephrotoxicity. It is dose-related and has become a chief limitation of its clinical use. The purpose of this study was to evaluate the preventive effect of ginseng extract (GE) and its active component, ginsenoside (GS), on cisplatin-induced nephrotoxicity.
Six-week-old female BALB/c mice were administered with 5 mg/kg of CDDP intraperitoneally once daily for 5 days. 125, 250, 500 mg/kg of GE or 5 mg/kg of GS Rb1, Rd, Rg1 were given orally once a day from 5 days before CDDP administration. GE and GS decreased urine N-acetyl-β-D-glucosaminidase (NAG), urine protein, blood urea nitrogen (BUN) and increased urine creatinine excretion at different level. All of the treatment groups ameliorated CDDP-induced renal morphological damage and diminished TNF-α deposited in injury tissue, while GE and GS Rg1 increased the expression of p21 and PCNA in renal cell.
Our findings demonstrated that GE and GS attenuate CDDP-induced nephrotixicity by inhibiting TNF-α expression and inducing cell cycle arrest to repair DNA damage. The effects of GE 250 mg/kg and GS Rg1 are the best among the concomitance groups.

目錄 I
圖目錄 V
表目錄 VII
縮寫表 i
中 文 摘 要 ii
Abstract iii
第一章 緒言 1
第二章 文獻回顧 4
第一節 順氯氨鉑（Cisplatin）的作用機轉及臨床使用 4
第二節 Cisplatin引起腎毒性的臨床表徵與機轉 9
第三節 Cisplatin與細胞週期的調控 15
第四節 人參及其藥效研究 24
第五節 人參皂苷Rb1、Rd及Rg1之藥效研究 29
5.1 人參皂苷之結構特性 29
5.2人參皂苷Rb1之藥效研究 32
5.3人參皂苷Rd之藥效研究 35
5.4人參皂苷Rg1之藥效研究 36
第三章 研究目的 37
第四章 材料與方法 38
第一節 人參濃縮劑在CDDP引起腎炎模型的藥效評估 38
1.1實驗動物 38
1.2實驗藥物 38
1.3人參濃縮劑在此腎炎模型之實驗設計 38
1.4尿液收集 39
1.5動物犧牲法、血液及組織切片製作 39
1.6尿中NAG、Creatinine及蛋白的含量分析 40
1.7血清中BUN值的含量測定 41
1.8 Periodoic acid-Schiff’s（PAS）stain組織染色 41
1.9組織損傷程度的量化 42
1.10免疫螢光染色（Immunofluorescence） 42
1.11統計方法 43
第二節 人參皂苷在CDDP引起腎炎模型的藥效評估 45
2.1實驗動物 45
2.2實驗藥物 45
2.3人參皂苷在此腎炎模型之實驗設計 45
2.4尿液收集：如前述第四章1.4 46
2.5動物犧牲法、血液及組織切片製作：如前述第四章1.5 46
2.6尿中NAG、Creatinine及蛋白的含量分析 46
2.7血清中BUN值的含量測定 46
2.8 Periodoic acid-Schiff’s（PAS）stain組織染色 46
2.9組織損傷程度的量化 46
2.10免疫螢光染色 46
2.11統計方法 46
第五章 結果 48
第一節 人參濃縮劑在CDDP引起腎炎模型的藥效評估 48
1.1 尿中NAG、Creatinine及蛋白的含量分析 48
1.2 血清中BUN分析 49
1.3 組織病理PAS染色 50
1.4組織損傷量化分析 50
1.5免疫螢光染色 50
1.5-1 TNF-α之表現 51
1.5-2 p21之表現 51
1.5-3 PCNA之表現 51
第二節 人參皂苷在CDDP引起腎炎模型的藥效評估 61
2.1 尿中NAG、Creatinine及蛋白的含量分析 61
2.2 血清中BUN分析 62
2.3 組織病理PAS染色 62
2.4組織損傷量化分析 63
2.5免疫螢光染色 63
2.5-1 TNF-α之表現 63
2.5-2 p21之表現 64
2.5-3 PCNA之表現 64
第六章 討論 73
第七章 結論 77
參考文獻 79

1.中華民國衛生署. 中華民國九十四年臺灣地區死因統計結果摘要 http://www.doh.gov.tw/statistic/index.htm. Accessed June 11th, 2007.
2.世界衛生組織. Cancer: diet and physical activity''s impact. Accessed June 11th, 2007.
3.Thomson Healthcare I. CAFFEINE. MICROMEDEX(R) Healthcare Series MICROMEDEX(R) Healthcare Series 2006.
4.de Jongh FE, van Veen RN, Veltman SJ, et al. Weekly high-dose cisplatin is a feasible treatment option: analysis on prognostic factors for toxicity in 400 patients. British Journal of Cancer. Apr 22 2003; 88(8):1199-1206.
5.Rosenberg B, Vancamp L, Krigas T. INHIBITION OF CELL DIVISION IN ESCHERICHIA COLI BY ELECTROLYSIS PRODUCTS FROM A PLATINUM ELECTRODE. Nature. Feb 13 1965; 205:698-699.
6.Jordan P, Carmo-Fonseca M. Molecular mechanisms involved in cisplatin cytotoxicity. Cellular & Molecular Life Sciences. Aug 2000; 57(8-9):1229-1235.
7.Muggia FM. Cisplatin update. Seminars in Oncology. Feb 1991; 18(1 Suppl 3):1-4.
8.Leng M, Brabec V. DNA adducts of cisplatin, transplatin and platinum-intercalating drugs. IARC Scientific Publications. 1994(125):339-348.
9.Chu G. Cellular responses to cisplatin. The roles of DNA-binding proteins and DNA repair. Journal of Biological Chemistry. Jan 14 1994; 269(2):787-790.
10.Ries F, Klastersky J. Nephrotoxicity induced by cancer chemotherapy with special emphasis on cisplatin toxicity. American Journal of Kidney Diseases. Nov 1986; 8(5):368-379.
11.Leibbrandt ME, Wolfgang GH, Metz AL, Ozobia AA, Haskins JR. Critical subcellular targets of cisplatin and related platinum analogs in rat renal proximal tubule cells. Kidney International. Sep 1995; 48(3):761-770.
12.Schrier RW. Diseases of the kidney and urinary tract. Vol 2. 7th ed ed: Philadelphia, PA, USA : Lippincott Williams & Wilkins; 2001.
13.Raymond J.M N, Jonh de vries, Mannfred A. Hollinger. Toxicologie: CRC press 1996.
14.Abeloff MD. Clinical Oncology 3rd ed. New York Churchill Livingstone; 2004.
15.Skeel RT. Handbook of Cancer Chemotherapy. Fifth Edition ed: Lippincott Williams & Wilkins; 1999.
16.Hartmann JT, Knop S, Fels LM, et al. The use of reduced doses of amifostine to ameliorate nephrotoxicity of cisplatin/ifosfamide-based chemotherapy in patients with solid tumors. Anti-Cancer Drugs. Jan 2000; 11(1):1-6.
17.Castiglione F, Dalla Mola A, Porcile G. Protection of normal tissues from radiation and cytotoxic therapy: the development of amifostine. Tumori. Mar-Apr 1999; 85(2):85-91.
18.Kuhlmann MK, Burkhardt G, Kohler H. Insights into potential cellular mechanisms of cisplatin nephrotoxicity and their clinical application. Nephrology Dialysis Transplantation. Dec 1997; 12(12):2478-2480.
19.Santini V, Giles FJ. The potential of amifostine: from cytoprotectant to therapeutic agent.[see comment]. Haematologica. Nov 1999; 84(11):1035-1042.
20.Schuchter LM, Hensley ML, Meropol NJ, Winer EP, American Society of Clinical Oncology Chemotherapy and Radiotherapy Expert P. 2002 update of recommendations for the use of chemotherapy and radiotherapy protectants: clinical practice guidelines of the American Society of Clinical Oncology. Journal of Clinical Oncology. Jun 15 2002; 20(12):2895-2903.
21.Daugaard G, Abildgaard U. Cisplatin nephrotoxicity. A review. Cancer Chemotherapy & Pharmacology. 1989; 25(1):1-9.
22.Choie DD, Longnecker DS, del Campo AA. Acute and chronic cisplatin nephropathy in rats. Laboratory Investigation. May 1981; 44(5):397-402.
23.Safirstein R, Winston J, Moel D, Dikman S, Guttenplan J. Cisplatin nephrotoxicity: insights into mechanism. International Journal of Andrology. Feb 1987; 10(1):325-346.
24.Meyer KB, Madias NE. Cisplatin nephrotoxicity. Mineral & Electrolyte Metabolism. 1994; 20(4):201-213.
25.Litterst CL TI, Guarino AM. Plasma levels and organ distribution of platinum in the rat, dog, and dog fish following intravenous administration of cis-DDP(ll) J Clin Hemat Oncol. 1977; 7:169.
26.Alex M. Davison JSC, Jean-pierre Grunfeld, David N.S. Kerr, Eberhard Ritz, Christopher G.Winearls. Oxford Textbook of Clinical Nephrology. Vol 3. 2th edition ed: Oxford ; New York : Oxford University Press; 1998.
27.Berns JS, Ford PA. Renal toxicities of antineoplastic drugs and bone marrow transplantation. Seminars in Nephrology. Jan 1997; 17(1):54-66.
28.Schilsky RL, Anderson T. Hypomagnesemia and renal magnesium wasting in patients receiving cisplatin. Annals of Internal Medicine. Jun 1979; 90(6):929-931.
29.Lam M, Adelstein DJ. Hypomagnesemia and renal magnesium wasting in patients treated with cisplatin. American Journal of Kidney Diseases. Sep 1986; 8(3):164-169.
30.Sutton RA, Walker VR, Halabe A, Swenerton K, Coppin CM. Chronic hypomagnesemia caused by cisplatin: effect of calcitriol. Journal of Laboratory & Clinical Medicine. Jan 1991; 117(1):40-43.
31.Winston JA, Safirstein R. Reduced renal blood flow in early cisplatin-induced acute renal failure in the rat. American Journal of Physiology. Oct 1985; 249(4 Pt 2):F490-496.
32.Safirstein R, Miller P, Dikman S, Lyman N, Shapiro C. Cisplatin nephrotoxicity in rats: defect in papillary hypertonicity. American Journal of Physiology. Aug 1981; 241(2):F175-185.
33.Arany I, Safirstein RL. Cisplatin nephrotoxicity. Seminars in Nephrology. Sep 2003; 23(5):460-464.
34.Lau AH. Apoptosis induced by cisplatin nephrotoxic injury. Kidney International. Oct 1999; 56(4):1295-1298.
35.Dobyan DC, Levi J, Jacobs C, Kosek J, Weiner MW. Mechanism of cis-platinum nephrotoxicity: II. Morphologic observations. Journal of Pharmacology & Experimental Therapeutics. Jun 1980;213(3):551-556.
36.Ross DA, Gale GR. Reduction of the renal toxicity of cis-dichlorodiammineplatinum(II) by probenecid. Cancer Treatment Reports. May 1979; 63(5):781-787.
37.Weiner MW, Jacobs C. Mechanism of cisplatin nephrotoxicity. Federation Proceedings. Oct 1983; 42(13):2974-2978.
38.Fatima S, Yusufi AN, Mahmood R. Effect of cisplatin on renal brush border membrane enzymes and phosphate transport. Human & Experimental Toxicology. Dec 2004; 23(12):547-554.
39.Tsuruya K, Tokumoto M, Ninomiya T, et al. Antioxidant ameliorates cisplatin-induced renal tubular cell death through inhibition of death receptor-mediated pathways. American Journal of Physiology - Renal Physiology. Aug 2003; 285(2):F208-218.
40.Levi J, Jacobs C, Kalman SM, McTigue M, Weiner MW. Mechanism of cis-platinum nephrotoxicity: I. Effects of sulfhydryl groups in rat kidneys. Journal of Pharmacology & Experimental Therapeutics. Jun 1980; 213(3):545-550.
41.Ramesh G, Reeves WB. Inflammatory cytokines in acute renal failure. Kidney International - Supplement. Oct 2004(91):S56-61.
42.Kaushal GP, Kaushal V, Hong X, et al. Role and regulation of activation of caspases in cisplatin-induced injury to renal tubular epithelial cells. Kidney International. Nov 2001; 60(5):1726-1736.
43.Nowak G. Protein kinase C-alpha and ERK1/2 mediate mitochondrial dysfunction, decreases in active Na+ transport, and cisplatin-induced apoptosis in renal cells. Journal of Biological Chemistry. Nov 8 2002; 277(45):43377-43388.
44.Rosenberg JM, Sato PH. Cisplatin inhibits in vitro translation by preventing the formation of complete initiation complex. Molecular Pharmacology. Mar 1993; 43(3):491-497.
45.Courjault-Gautier F, Le Grimellec C, Giocondi MC, Toutain HJ. Modulation of sodium-coupled uptake and membrane fluidity by cisplatin in renal proximal tubular cells in primary culture and brush-border membrane vesicles. Kidney International. Apr 1995; 47(4):1048-1056.
46.Bompart G. Cisplatin-induced changes in cytochrome P-450, lipid peroxidation and drug-metabolizing enzyme activities in rat kidney cortex. Toxicology Letters. Aug 1989; 48(2):193-199.
47.Mistry P, Merazga Y, Spargo DJ, Riley PA, McBrien DC. The effects of cisplatin on the concentration of protein thiols and glutathione in the rat kidney. Cancer Chemotherapy & Pharmacology. 1991; 28(4):277-282.
48.Galle J. Oxidative stress in chronic renal failure.[comment]. Nephrology Dialysis Transplantation. Nov 2001; 16(11):2135-2137.
49.Shackelford RE, Kaufmann WK, Paules RS. Oxidative stress and cell cycle checkpoint function. Free Radical Biology & Medicine. May 1 2000; 28(9):1387-1404.
50.Ichikawa I, Kiyama S, Yoshioka T. Renal antioxidant enzymes: their regulation and function. Kidney International. Jan 1994; 45(1):1-9.
51.Halliwell B. The role of oxygen radicals in human disease, with particular reference to the vascular system. Haemostasis. Mar 1993; 23 Suppl 1:118-126.
52.Halliwell B. Antioxidant defence mechanisms: from the beginning to the end (of the beginning). Free Radical Research. Oct 1999; 31(4):261-272.
53.Klahr S. Oxygen radicals and renal diseases. Mineral & Electrolyte Metabolism. 1997; 23(3-6):140-143.
54.Sugiyama S, Hayakawa M, Kato T, Hanaki Y, Shimizu K, Ozawa T. Adverse effects of anti-tumor drug, cisplatin, on rat kidney mitochondria: disturbances in glutathione peroxidase activity. Biochemical & Biophysical Research Communications. Mar 31 1989;159(3):1121-1127.
55.Schrier RW. Cancer therapy and renal injury.[comment]. Journal of Clinical Investigation. Sep 2002; 110(6):743-745.
56.Ramesh G, Reeves WB. TNFR2-mediated apoptosis and necrosis in cisplatin-induced acute renal failure. American Journal of Physiology - Renal Physiology. Oct 2003; 285(4):F610-618.
57.Ramesh G, Reeves WB, Ramesh G, Reeves WB. TNF-alpha mediates chemokine and cytokine expression and renal injury in cisplatin nephrotoxicity.[see comment]. Journal of Clinical Investigation. Sep 2002; 110(6):835-842.
58.Goossens V, Grooten J, De Vos K, Fiers W. Direct evidence for tumor necrosis factor-induced mitochondrial reactive oxygen intermediates and their involvement in cytotoxicity. Proceedings of the National Academy of Sciences of the United States of America. Aug 29 1995;92(18):8115-8119.
59.丁明孝等編著. 細胞分子生物學. 第一版 ed. 台北市: 九州圖書文物有限公司; 2001.
60.Lewin B. Genes VIII: Pearson Prentice Hall; 2004.
61.Price PM, Megyesi J, Safirstein RL. Cell cycle regulation: repair and regeneration in acute renal failure. Seminars in Nephrology. Sep 2003; 23(5):449-459.
62.Megyesi J, Udvarhelyi N, Safirstein RL, Price PM. The p53-independent activation of transcription of p21 WAF1/CIP1/SDI1 after acute renal failure. American Journal of Physiology. Dec 1996; 271(6 Pt 2):F1211-1216.
63.Megyesi J, Andrade L, Vieira JM, Jr., Safirstein RL, Price PM. Positive effect of the induction of p21WAF1/CIP1 on the course of ischemic acute renal failure. Kidney International. Dec 2001; 60(6):2164-2172.
64.Nowak G, Price PM, Schnellmann RG. Lack of a functional p21WAF1/CIP1 gene accelerates caspase-independent apoptosis induced by cisplatin in renal cells. American Journal of Physiology - Renal Physiology. Sep 2003; 285(3):F440-450.
65.Megyesi J, Safirstein RL, Price PM, Megyesi J, Safirstein RL, Price PM. Induction of p21WAF1/CIP1/SDI1 in kidney tubule cells affects the course of cisplatin-induced acute renal failure. Journal of Clinical Investigation. Feb 15 1998; 101(4):777-782.
66.Yasuda H, Kato A, Miyaji T, Zhou H, Togawa A, Hishida A. Insulin-like growth factor-I increases p21 expression and attenuates cisplatin-induced acute renal injury in rats. Clinical & Experimental Nephrology. Mar 2004; 8(1):27-35.
67.Price PM, Safirstein RL, Megyesi J. Protection of renal cells from cisplatin toxicity by cell cycle inhibitors. American Journal of Physiology - Renal Physiology. Feb 2004; 286(2):F378-384.
68.Zhou H, Kato A, Yasuda H, et al. The induction of cell cycle regulatory and DNA repair proteins in cisplatin-induced acute renal failure. Toxicology & Applied Pharmacology. Oct 15 2004;200(2):111-120.
69.Miyaji T, Kato A, Yasuda H, et al. Role of the increase in p21 in cisplatin-induced acute renal failure in rats. Journal of the American Society of Nephrology. May 2001; 12(5):900-908.
70.Lin Z, Lim S, Viani MA, Sapp M, Lim MS. Down-regulation of telomerase activity in malignant lymphomas by radiation and chemotherapeutic agents.[see comment]. American Journal of Pathology. Aug 2001;159(2):711-719.
71.Shankland SJ, Wolf G, Shankland SJ, Wolf G. Cell cycle regulatory proteins in renal disease: role in hypertrophy, proliferation, and apoptosis. American Journal of Physiology - Renal Physiology. Apr 2000; 278(4):F515-529.
72.Benjamin L. Genes VII. 2000.
73.Kelman Z. PCNA: structure, functions and interactions. Oncogene. Feb 13 1997; 14(6):629-640.
74.Miyachi K, Fritzler MJ, Tan EM. Autoantibody to a nuclear antigen in proliferating cells. Journal of Immunology. Dec 1978; 121(6):2228-2234.
75.Bravo R, Celis JE. A search for differential polypeptide synthesis throughout the cell cycle of HeLa cells. Journal of Cell Biology. Mar 1980; 84(3):795-802.
76.Maga G, Hubscher U. Proliferating cell nuclear antigen (PCNA): a dancer with many partners. Journal of Cell Science. Aug 1 2003; 116(Pt 15):3051-3060.
77.Nakajima T, Miyaji T, Kato A, Ikegaya N, Yamamoto T, Hishida A. Uninephrectomy reduces apoptotic cell death and enhances renal tubular cell regeneration in ischemic ARF in rats. American Journal of Physiology. Oct 1996; 271(4 Pt 2):F846-853.
78.Sano K, Fujigaki Y, Miyaji T, et al. Role of apoptosis in uranyl acetate-induced acute renal failure and acquired resistance to uranyl acetate. Kidney International. Apr 2000; 57(4):1560-1570.
79.McCormick D, Hall PA, McCormick D, Hall PA. The complexities of proliferating cell nuclear antigen. Histopathology. Dec 1992; 21(6):591-594.
80.Celis JE, Madsen P, Celis JE, Madsen P. Increased nuclear cyclin/PCNA antigen staining of non S-phase transformed human amnion cells engaged in nucleotide excision DNA repair. FEBS Letters. Dec 15 1986; 209(2):277-283.
81.賴榮祥. 原色生藥學. 台中市: 創譯出版社; 2000.
82.Attele AS, Wu JA, Yuan CS. Ginseng pharmacology: multiple constituents and multiple actions. Biochemical Pharmacology. Dec 1 1999; 58(11):1685-1693.
83.Liu H, Baliga R. Cytochrome P450 2E1 null mice provide novel protection against cisplatin-induced nephrotoxicity and apoptosis. Kidney International. May 2003; 63(5):1687-1696.
84.Kiefer D, Pantuso T. Panax ginseng.[see comment]. American Family Physician. Oct 15 2003; 68(8):1539-1542.
85.Kitts D, Hu C. Efficacy and safety of ginseng. Public Health Nutrition. Dec 2000; 3(4A):473-485.
86.Chang YS, Seo EK, Gyllenhaal C, Block KI. Panax ginseng: a role in cancer therapy? Integrative Cancer Therapies. Mar 2003; 2(1):13-33.
87.Shin HR, Kim JY, Yun TK, Morgan G, Vainio H. The cancer-preventive potential of Panax ginseng: a review of human and experimental evidence. Cancer Causes & Control. Jul 2000; 11(6):565-576.
88.Ong YC, Yong EL. Panax (ginseng)--panacea or placebo? Molecular and cellular basis of its pharmacological activity. Annals of the Academy of Medicine, Singapore. Jan 2000; 29(1):42-46.
89.Gillis CN. Panax ginseng pharmacology: a nitric oxide link? Biochemical Pharmacology. Jul 1 1997; 54(1):1-8.
90.Vogler BK, Pittler MH, Ernst E. The efficacy of ginseng. A systematic review of randomised clinical trials. European Journal of Clinical Pharmacology. Oct 1999; 55(8):567-575.
91.Rimar S, Lee-Mengel M, Gillis CN. Pulmonary protective and vasodilator effects of a standardized Panax ginseng preparation following artificial gastric digestion. Pulmonary Pharmacology. Aug 1996; 9(4):205-209.
92.Voces J, Alvarez AI, Vila L, Ferrando A, Cabral de Oliveira C, Prieto JG. Effects of administration of the standardized Panax ginseng extract G115 on hepatic antioxidant function after exhaustive exercise. Comparative Biochemistry & Physiology Part C Pharmacology, Toxicology, Endocrinology. Jun 1999;123(2):175-184.
93.Sotaniemi EA, Haapakoski E, Rautio A. Ginseng therapy in non-insulin-dependent diabetic patients. Diabetes Care. Oct 1995; 18(10):1373-1375.
94.Jeong TC, Kim HJ, Park JI, et al. Protective effects of red ginseng saponins against carbon tetrachloride-induced hepatotoxicity in Sprague Dawley rats. Planta Medica. Apr 1997; 63(2):136-140.
95.Cho JY, Yoo ES, Baik KU, Park MH, Han BH. In vitro inhibitory effect of protopanaxadiol ginsenosides on tumor necrosis factor (TNF)-alpha production and its modulation by known TNF-alpha antagonists. Planta Medica. Apr 2001; 67(3):213-218.
96.Shin YW, Bae EA, Kim SS, Lee YC, Kim DH. Effect of ginsenoside Rb1 and compound K in chronic oxazolone-induced mouse dermatitis. International Immunopharmacology. Jul 2005; 5(7-8):1183-1191.
97.Lee HU, Bae EA, Han MJ, Kim NJ, Kim DH. Hepatoprotective effect of ginsenoside Rb1 and compound K on tert-butyl hydroperoxide-induced liver injury. Liver International. Oct 2005; 25(5):1069-1073.
98.Cho JY, Yoo ES, Baik KU, et al. In vitro inhibitory effect of protopanaxadiol ginsenosides on tumor necrosis factor (TNF)-alpha production and its modulation by known TNF-alpha antagonists. Planta Medica. Apr 2001;67(3):213-218.
99.Ohashi R, Yan S, Mu H, et al. Effects of homocysteine and ginsenoside Rb1 on endothelial proliferation and superoxide anion production. Journal of Surgical Research. Jun 15 2006; 133(2):89-94.
100.Zhou W, Chai H, Lin PH, Lumsden AB, Yao Q, Chen C. Ginsenoside Rb1 blocks homocysteine-induced endothelial dysfunction in porcine coronary arteries. Journal of Vascular Surgery. May 2005; 41(5):861-868.
101.Yu J, Eto M, Akishita M, Kaneko A, Ouchi Y, Okabe T. Signaling pathway of nitric oxide production induced by ginsenoside Rb1 in human aortic endothelial cells: a possible involvement of androgen receptor. Biochemical & Biophysical Research Communications. Feb 16 2007; 353(3):764-769.
102.Deng HL, Zhang JT. Anti-lipid peroxilative effect of ginsenoside Rb1 and Rg1. Chinese Medical Journal. May 1991; 104(5):395-398.
103.Park JK, Namgung U, Lee CJ, et al. Calcium-independent CaMKII activity is involved in ginsenoside Rb1-mediated neuronal recovery after hypoxic damage. Life Sciences. Jan 14 2005;76(9):1013-1025.
104.Mook-Jung I, Hong HS, Boo JH, et al. Ginsenoside Rb1 and Rg1 improve spatial learning and increase hippocampal synaptophysin level in mice. Journal of Neuroscience Research. Mar 15 2001; 63(6):509-515.
105.Yokozawa T, Liu ZW, Dong E. A study of ginsenoside-Rd in a renal ischemia-reperfusion model. Nephron. 1998; 78(2):201-206.
106.Yokozawa T, Owada S. Effect of ginsenoside-Rd in cephaloridine-induced renal disorder. Nephron. Feb 1999; 81(2):200-207.
107.Yokozawa T, Liu ZW. The role of ginsenoside-Rd in cisplatin-induced acute renal failure. Renal Failure. Mar 2000; 22(2):115-127.
108.Yokozawa T, Dong E. Role of ginsenoside-Rd in cisplatin-induced renal injury: special reference to DNA fragmentation. Nephron. Dec 2001; 89(4):433-438.
109.Yokozawa T, Satoh A, Cho EJ. Ginsenoside-Rd attenuates oxidative damage related to aging in senescence-accelerated mice. Journal of Pharmacy & Pharmacology. Jan 2004; 56(1):107-113.
110.Cheng Y, Shen LH, Zhang JT. Anti-amnestic and anti-aging effects of ginsenoside Rg1 and Rb1 and its mechanism of action. Acta Pharmacologica Sinica. Feb 2005; 26(2):143-149.
111.Chen XC, Zhou YC, Chen Y, Zhu YG, Fang F, Chen LM. Ginsenoside Rg1 reduces MPTP-induced substantia nigra neuron loss by suppressing oxidative stress. Acta Pharmacologica Sinica. Jan 2005; 26(1):56-62.
112.Chen XC, Zhu YG, Zhu LA, et al. Ginsenoside Rg1 attenuates dopamine-induced apoptosis in PC12 cells by suppressing oxidative stress. European Journal of Pharmacology. Jul 18 2003; 473(1):1-7.
113.Chen XC, Fang F, Zhu YG, Chen LM, Zhou YC, Chen Y. Protective effect of ginsenoside Rg1 on MPP+-induced apoptosis in SHSY5Y cells. Journal of Neural Transmission. Aug 2003; 110(8):835-845.
114.Leung KW, Cheng YK, Mak NK, Chan KK, Fan TP, Wong RN. Signaling pathway of ginsenoside-Rg1 leading to nitric oxide production in endothelial cells. FEBS Letters. May 29 2006; 580(13):3211-3216.
115.Lu JP, Ma ZC, Yang J, Huang J, Wang SR, Wang SQ. Ginsenoside Rg1-induced alterations in gene expression in TNF-alpha stimulated endothelial cells. Chinese Medical Journal. Jun 2004; 117(6):871-876.
116.Zhang HS, Wang SQ. Ginsenoside Rg1 inhibits tumor necrosis factor-alpha (TNF-alpha)-induced human arterial smooth muscle cells (HASMCs) proliferation. Journal of Cellular Biochemistry. Aug 15 2006; 98(6):1471-1481.
117.Kim YW, Song DK, Kim WH, et al. Long-term oral administration of ginseng extract decreases serum gamma-globulin and IgG1 isotype in mice. Journal of Ethnopharmacology. Sep 1997; 58(1):55-58.
118.Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Analytical Biochemistry. May 7 1976; 72:248-254.
119.張惠婷. 順氯氨鉑引發的腎毒性在純系小鼠的確立與柴胡在此腎炎模型的藥效評估. 台北市: 藥學系碩士班, 臺北醫學大學; 2005.
120.Jones BR, Bhalla RB, Mladek J, et al. Comparison of methods of evaluating nephrotoxicity of cis-platinum. Clinical Pharmacology & Therapeutics. Apr 1980; 27(4):557-562.
121.Hultberg B, Ravnskov U. The excretion of N-acetyl-beta-glucosaminidase in glomerulonephritis. Clinical Nephrology. Jan 1981; 15(1):33-38.
122.Yokozawa T, Zhou JJ, Hattori M, et al. Effects of ginseng in nephrectomized rats. Biological & Pharmaceutical Bulletin. Nov 1994; 17(11):1485-1489.
123.Wu CF, Bi XL, Yang JY, et al. Differential effects of ginsenosides on NO and TNF-alpha production by LPS-activated N9 microglia. International Immunopharmacology. Mar 2007; 7(3):313-320.
124.Wang Y, Wang BX, Liu TH, et al. Metabolism of ginsenoside Rg1 by intestinal bacteria. II. Immunological activity of ginsenoside Rg1 and Rh1. Acta Pharmacologica Sinica. Sep 2000; 21(9):792-796.
125.Park EK, Choo MK, Han MJ, Kim DH. Ginsenoside Rh1 possesses antiallergic and anti-inflammatory activities. International Archives of Allergy & Immunology. Feb 2004; 133(2):113-120.
126.Shin YW, Bae EA, Kim SS, et al. Effect of ginsenoside Rb1 and compound K in chronic oxazolone-induced mouse dermatitis. International Immunopharmacology. Jul 2005; 5(7-8):1183-1191.
127.Park EK, Shin YW, Lee HU, et al. Inhibitory effect of ginsenoside Rb1 and compound K on NO and prostaglandin E2 biosyntheses of RAW264.7 cells induced by lipopolysaccharide. Biological & Pharmaceutical Bulletin. Apr 2005; 28(4):652-656.
128.Han SW, Kim H. Ginsenosides stimulate endogenous production of nitric oxide in rat kidney. International Journal of Biochemistry & Cell Biology. May 1996; 28(5):573-580.
129.Hattori T, Ito M, Suzuki Y, Hattori T, Ito M, Suzuki Y. [Studies on antinephritic effects of plant components in rats (2): Effects of ginsenosides on original-type anti-GBM nephritis in rats and its mechanisms]. Nippon Yakurigaku Zasshi - Folia Pharmacologica Japonica. Feb 1991;97(2):127-134.