跳到主要內容

臺灣博碩士論文加值系統

(18.97.14.86) 您好!臺灣時間:2025/03/20 07:28
字體大小: 字級放大   字級縮小   預設字形  
回查詢結果 :::

詳目顯示

我願授權國圖
: 
twitterline
研究生:林盈君
研究生(外文):Ying-Jyun Lin
論文名稱:14-脫氧-11,12-雙脫氫穿心蓮內酯對大鼠初代肝細胞藥物代謝酵素及膜轉運蛋白表現的影響
論文名稱(外文):14-脫氧-11,12-雙脫氫穿心蓮內酯對大鼠初代肝細胞藥物代謝酵素及膜轉運蛋白表現的影響
指導教授:李宗貴
學位類別:碩士
校院名稱:中國醫藥大學
系所名稱:營養學系碩士班
學門:醫藥衛生學門
學類:營養學類
論文種類:學術論文
論文出版年:2016
畢業學年度:104
語文別:中文
論文頁數:59
中文關鍵詞:14-脫氧-1112-雙脫氫穿心蓮內酯藥物代謝系統aryl hydrocarbon receptorconstitutive androstane receptorpregnane X receptorNF-E2-related factor 2初代肝細胞大鼠
外文關鍵詞:14-deoxy-1112-didehydroandrographolidedrug metabolizing systemaryl hydrocarbon receptorconstitutive androstane receptorpregnane X receptorNF-E2-related factor 2primary hepatocytesrat
相關次數:
  • 被引用被引用:0
  • 點閱點閱:168
  • 評分評分:
  • 下載下載:0
  • 收藏至我的研究室書目清單書目收藏:0
人體每天都會接觸到無數的外來物質,從食物中的天然成分到對環境有害之物質,它們需藉由體內藥物代謝系統代謝,將之轉變成親水性之代謝產物,以利排出體外,減少對身體之傷害。穿心蓮為一種廣泛使用於亞洲地區的傳統中草藥植物,具有抗發炎、抗病毒及保肝等療效。14-脫氧-11,12-雙脫氫穿心蓮內酯(14-Deoxy-11,12-didehydroandrographolide, deAND)是穿心蓮萃取物中最具生物活性的主要成分之一,已有研究指出其具有降血壓、抗發炎、抗病毒等療效。本篇研究以大鼠初代肝細胞為實驗模式,目的在探討14-脫氧-11,12-雙脫氫穿心蓮內酯對藥物代謝酵素系統的影響,及其可能作用機轉。免疫墨漬法分析結果顯示,14-脫氧-11,12-雙脫氫穿心蓮內酯(2.5、5、10 μM)劑量依賴關係增加Phase I酵素(CYP1A1、CYP1A2、2C6、3A1、3A2)、Phase II酵素(GSTP、NQO1 、UGT1A1)、Phase III膜轉運蛋白(MRP2、P-gp、OATP2B1)的表現;14-脫氧-11,12-雙脫氫穿心蓮內酯也可增加核受體aryl hydrocarbon receptor (AhR)、constitutive androstane receptor (CAR)和pregnane X receptor (PXR)暨轉錄因子NF-E2-related factor 2 (Nrf2)轉位入核,EMSA進一步證實14-脫氧-11,12-雙脫氫穿心蓮內酯可以活化AhR、PXR和Nrf2的DNA結合活性;14-脫氧-11,12-雙脫氫穿心蓮內酯增加Akt、p38和JNK磷酸化,預處理Akt抑制劑(LY294002)、p38抑制劑(SB203580)和JNK抑制劑(SP600125)可抑制14-脫氧-11,12-雙脫氫穿心蓮內酯誘發的Nrf2轉位入核,Akt抑制劑LY294002也會逆轉14-脫氧-11,12-雙脫氫穿心蓮內酯誘發UGT1A1和GSTP表現,p38抑制劑SB203580則可逆轉14-脫氧-11,12-雙脫氫穿心蓮內酯誘發UGT1A1表現。siRNA技術阻斷AhR mRNA表現後,14-脫氧-11,12-雙脫氫穿心蓮內酯誘發CYP1A1和CYP1A2表現會被抑制。綜合上述結果,14-脫氧-11,12-雙脫氫穿心蓮內酯可透過活化核受體AhR、CAR和PXR暨轉錄因Nrf2上調藥物代謝酵素和膜轉運蛋白表現,且Nrf2的核轉位與Akt、p38訊息活化有關。

The human body is exposed to a wide array of xenobiotics in one’s lifetime, from food components to environmental toxins. To protect against chemical insults, converting these potent toxic substances into hydrophilic metabolites by drug-metabolizing system is necessary. Andrographis paniculata is a commonly used traditional herb medicine for cold, infection, and hypoglycemia in many Southeast Asian countries. Evidence indicates A. paniculata has a variety of biological activities, including anti-inflammatory, antiviral, hepatoprotective effects and so on. 14-Deoxy-11,12-didehydroandrographolide (deAND), a diterpenoid, is one of the bioactive components in Andrographis paniculata. In the present study, we investigated whether deAND modulates the expression of drug metabolizing enzymes and membrane transporters in rat primary hepatocytes and the possible mechanism involved. Western blotting revealed that deAND (2.5, 5, 10 μM) dose-depentdently increases CYP1A1, CYP1A2, CYP2C6, CYP3A1 and CYP3A2 (Phase I enzymes), UGT1A1, NQO1, GSTP (Phase II enzymes), MRP2, P-gp, and OATP2B1 (Phase III membrane transporters) protein expression. deAND increased the nuclear translocation of aryl hydrocarbon receptor ( AhR ), constitutive androstane receptor (CAR), pregnane X receptor ( PXR ), and NF-E2-related factor 2 (Nrf2). EMSA demonstrated that deAND enhances the DNA binding activity of nuclear AhR, PXR and Nrf2. With deAND treatment, a time-dependently increase in Akt, p38, and JNK phosphorylation was noted. Pretreatment with Akt inhibitor LY294002, p38 inhibitor SB203580, and JNK inhibitor SP600125 suppressed deAND-induced Nrf2 nuclear translocation. In addition, pretreatment with Akt inhibitor (LY294002) reversed deAND-induced UGT1A1 and GSTP expression, and p38 inhibitor (SB203580) reversed deAND-induced UGT1A1 expression. Furthermore, AhR knockdown attenuated deAND-induced CYP1A1/2 expression. Taken together, these results suggested that deAND upregulated the transcription of drug-metabolizing enzyme and membrane transporter genes through activation of AhR, CAR, PXR, and Nrf2. deAND activation of Nrf2 is dependent on Akt and p38 signaling.

目錄 I
圖目錄 III
表目錄 V
縮寫表 VI
中文摘要 VII
英文摘要 VIII
第一章 前言 1
第二章 文獻探討 2
第一節、穿心蓮及14-脫氧-11,12-雙脫氫穿心蓮內酯 2
一、穿心蓮(Andrographis paniculata)之簡介 2
二、14-脫氧-11,12-雙脫氫穿心蓮內酯(14-Deoxy-11,12-didehydroandrographolide)生理功能 4
第二節、生物轉換系統(Biotransformation system) 7
一、第一階段酵素系統 (Phase I enzyme system) 8
二、第二階段酵素系統 (Phase II enzyme system) 11
三、第三階段膜轉運蛋白系統 (Phase III membrane transporter system) 14
四、藥物代謝酵素及膜轉運蛋白之調控 16
第三節、中草藥-藥物交互作用(herb-drug interaction) 21
第三章 研究動機與目的 22
第四章 實驗架構 23
第五章 材料與方法 24
第一節、實驗材料 24
第二節、實驗方法 29
一、大白鼠初代肝細胞之分離與培養 29
二、細胞培養時14-脫氧-11,12-雙脫氫穿心蓮內酯的濃度變化量分析 30
三、細胞存活率分析(MTT assay) 30
四、蛋白質表現分析-西方墨點法 (Western blotting) 31
五、Electrophoretic mobility shift assay (EMSA) 34
六、siRNA transfection 36
七、統計 37
第六章 結果 38
一、14-脫氧-11,12-雙脫氫穿心蓮內酯在細胞培養時之濃度變化量 38
二、14-脫氧-11,12-雙脫氫穿心蓮內酯對大鼠初代肝細胞存活率之影響 38
三、14-脫氧-11,12-雙脫氫穿心蓮內酯對大鼠初代肝細胞Phase I、 Phase II酵素蛋白和 Phase III膜轉運蛋白表現之影響 38
四、14-脫氧-11,12-雙脫氫穿心蓮內酯對AhR、CAR、PXR和Nrf2核轉位之影響 38
五、14-脫氧-11,12-雙脫氫穿心蓮內酯對AhR、 Nrf2和PXR的DNA結合活性之影響 39
六、14-脫氧-11,12-雙脫氫穿心蓮內酯對Akt及MAPK kinase磷酸化之影響 39
七、Akt與MAPK抑制劑對14-脫氧-11,12-雙脫氫穿心蓮內酯誘發Nrf2核轉位之影響及Phase II酵素表現之影響 39
八、AhR siRNA轉殖對CYP1A1和1A2蛋白質表現的影響 39
第七章 討論 48
第八章 結論 51
參考文獻 52



Abe, T., Kakyo, M., Tokui, T., Nakagomi, R., Nishio, T., Nakai, D., Nomura, H., Unno, M., Suzuki, M., and Naitoh, T. (1999). Identification of a novel gene family encoding human liver-specific organic anion transporter LST-1. Journal of Biological Chemistry 274, 17159-17163.
Alam, J., Stewart, D., Touchard, C., Boinapally, S., Choi, A.M., and Cook, J.L. (1999). Nrf2, a Cap’n’Collar transcription factor, regulates induction of the heme oxygenase-1 gene. Journal of Biological Chemistry 274, 26071-26078.
Arenas-Huertero, F., Villeda-Cuevas, D., Ap?龜iga-Vega, E., Miguel-P?臆ez, G., and Trillo-Tinoco, J. (2011). Molecular markers associated with the biological response to aromatic hydrocarbons from urban air in humans (INTECH Open Access Publisher).
Awang, K., Abdullah, N.H., Hadi, A.H.A., and Su Fong, Y. (2012). Cardiovascular activity of labdane diterpenes from Andrographis paniculata in isolated rat hearts. BioMed Research International 2012.
Bessems, J.G., and Vermeulen, N.P. (2001). Paracetamol (acetaminophen)-induced toxicity: molecular and biochemical mechanisms, analogues and protective approaches. Critical reviews in toxicology 31, 55-138.
Bindoli, A., Valente, M., and Cavallini, L. (1985). Inhibition of lipid peroxidation by alpha-tocopherolquinone and alpha-tocopherolhydroquinone. Biochemistry international 10, 753-761.
Bock, K.W. (2003). Vertebrate UDP-glucuronosyltransferases: functional and evolutionary aspects. Biochemical pharmacology 66, 691-696.
Bradfield, C.A., and Poland, A. (1988). A competitive binding assay for 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin and related ligands of the Ah receptor. Molecular pharmacology 34, 682-688.
Cai, W., Li, Y., Chen, S., Wang, M., Zhang, A., Zhou, H., Chen, H., and Jin, M. (2015). 14-Deoxy-11, 12-dehydroandrographolide exerts anti-influenza A virus activity and inhibits replication of H5N1 virus by restraining nuclear export of viral ribonucleoprotein complexes. Antiviral research 118, 82-92.
Canaparo, R., Finnstr?卌, N., Serpe, L., Nordmark, A., Muntoni, E., Eandi, M., Rane, A., and Zara, G.P. (2007). Expression of CYP3A isoforms and P?駪lycoprotein in human stomach, jejunum and ileum. Clinical and Experimental Pharmacology and Physiology 34, 1138-1144.
Chang, K.-T., Lii, C.-K., Tsai, C.-W., Yang, A.-J., and Chen, H.-W. (2008). Modulation of the expression of the π class of glutathione S-transferase by Andrographis paniculata extracts and andrographolide. Food and chemical toxicology 46, 1079-1088.
Chao, W.-W., and Lin, B.-F. (2010). Review Isolation and identification of bioactive compounds in Andrographis paniculata (Chuanxinlian). growth 10, 44.
Chen, H.-W., Huang, C.-S., Liu, P.-F., Li, C.-C., Chen, C.-T., Liu, C.-T., Chiang, J.-R., Yao, H.-T., and Lii, C.-K. (2013). Andrographis paniculata extract and andrographolide modulate the hepatic drug metabolism system and plasma tolbutamide concentrations in rats. Evidence-Based Complementary and Alternative Medicine 2013.
De Kanter, R., Olinga, P., De Jager, M., Merema, M., Meijer, D., and Groothius, G. (1999). Organ slices as an in vitro test system for drug metabolism in human liver, lung and kidney. Toxicology in vitro 13, 737-744.
Dragan, Y., Campbell, H., Baker, K., Vaughan, J., Mass, M., and Pilot, H. (1994). Focal and non-focal hepatic expression of placental glutathione S-transferase in carcinogen-treated rats. Carcinogenesis 15, 2587-2591.
Eggler, A.L., Liu, G., Pezzuto, J.M., van Breemen, R.B., and Mesecar, A.D. (2005). Modifying specific cysteines of the electrophile-sensing human Keap1 protein is insufficient to disrupt binding to the Nrf2 domain Neh2. Proceedings of the National Academy of Sciences of the United States of America 102, 10070-10075.
Falkner, K., Pinaire, J., Xiao, G.-H., Geoghegan, T., and Prough, R. (2001). Regulation of the rat glutathione S-transferase A2 gene by glucocorticoids: involvement of both the glucocorticoid and pregnane X receptors. Molecular pharmacology 60, 611-619.
Forman, B.M., Tzameli, I., Choi, H.-S., Chen, J., Simha, D., Seol, W., Evans, R.M., and Moore, D.D. (1998). Androstane metabolites bind to and deactivate the nuclear receptor CAR-β. Nature 395, 612-615.
Geick, A., Eichelbaum, M., and Burk, O. (2001). Nuclear receptor response elements mediate induction of intestinal MDR1 by rifampin. Journal of Biological Chemistry 276, 14581-14587.
Giacomini, K.M., Huang, S.-M., Tweedie, D.J., Benet, L.Z., Brouwer, K.L., Chu, X., Dahlin, A., Evers, R., Fischer, V., and Hillgren, K.M. (2010). Membrane transporters in drug development. Nature reviews Drug discovery 9, 215-236.
Grube, M., K?丱k, K., Karner, S., Reuther, S., Ritter, C.A., Jedlitschky, G., and Kroemer, H.K. (2006). Modification of OATP2B1-mediated transport by steroid hormones. Molecular pharmacology 70, 1735-1741.
Guan, S.-P., Kong, L.-R., Cheng, C., Lim, J.C., and Wong, W.F. (2011). Protective role of 14-deoxy-11, 12-didehydroandrographolide, a noncytotoxic analogue of andrographolide, in allergic airway inflammation. Journal of natural products 74, 1484-1490.
Guengerich, F. (2004). Cytochrome P450: what have we learned and what are the future issues? Drug metabolism reviews 36, 159-197.
Guengerich, F., and MacDonald, T. (1990). Mechanisms of cytochrome P-450 catalysis. The FASEB journal 4, 2453-2459.
Guengerich, F.P. (2000). Metabolism of chemical carcinogens. Carcinogenesis 21, 345-351.
Hahn, M.E. (1998). The aryl hydrocarbon receptor: a comparative perspective. Comparative Biochemistry and Physiology Part C: Pharmacology, Toxicology and Endocrinology 121, 23-53.
Hayes, J.D., Flanagan, J.U., and Jowsey, I.R. (2005). Glutathione transferases. Annu Rev Pharmacol Toxicol 45, 51-88.
Hayes, J.D., and Pulford, D.J. (1995). The Glut athione S-Transferase Supergene Family: Regulation of GST and the Contribution of the lsoenzymes to Cancer Chemoprotection and Drug Resistance Part II. Critical reviews in biochemistry and molecular biology 30, 521-600.
Hoffmeyer, S., Burk, O., Von Richter, O., Arnold, H., Brockm?匜ler, J., Johne, A., Cascorbi, I., Gerloff, T., Roots, I., and Eichelbaum, M. (2000). Functional polymorphisms of the human multidrug-resistance gene: multiple sequence variations and correlation of one allele with P-glycoprotein expression and activity in vivo. Proceedings of the National Academy of Sciences 97, 3473-3478.
Hoivik, D., Wilson, C., Wang, W., Willett, K., Barhoumi, R., Burghardt, R., and Safe, S. (1997). Studies on the Relationship between Estrogen Receptor Content, GlutathioneS-Transferase π Expression, and Induction by 2, 3, 7, 8-Tetrachlorodibenzo-p-dioxin and Drug Resistance in Human Breast Cancer Cells. Archives of biochemistry and biophysics 348, 174-182.
Honkakoski, P., Zelko, I., Sueyoshi, T., and Negishi, M. (1998). The nuclear orphan receptor CAR-retinoid X receptor heterodimer activates the phenobarbital-responsive enhancer module of the CYP2B gene. Molecular and cellular biology 18, 5652-5658.
Huang, H.-C., Nguyen, T., and Pickett, C.B. (2000). Regulation of the antioxidant response element by protein kinase C-mediated phosphorylation of NF-E2-related factor 2. Proceedings of the National Academy of Sciences 97, 12475-12480.
Huang, H.-C., Nguyen, T., and Pickett, C.B. (2002). Phosphorylation of Nrf2 at Ser-40 by protein kinase C regulates antioxidant response element-mediated transcription. Journal of Biological Chemistry 277, 42769-42774.
Ihunnah, C.A., Jiang, M., and Xie, W. (2011). Nuclear receptor PXR, transcriptional circuits and metabolic relevance. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease 1812, 956-963.
Itoh, K., Chiba, T., Takahashi, S., Ishii, T., Igarashi, K., Katoh, Y., Oyake, T., Hayashi, N., Satoh, K., and Hatayama, I. (1997). An Nrf2/small Maf heterodimer mediates the induction of phase II detoxifying enzyme genes through antioxidant response elements. Biochemical and biophysical research communications 236, 313-322.
Jančov??, P., and Šiller, M. (2012). Phase II Drug Metabolism. In Topics on Drug Metabolism, InTech, pp. 35-60.
Jancova, P., Anzenbacher, P., and Anzenbacherova, E. (2010). Phase II drug metabolizing enzymes. Biomedical Papers 154, 103-116.
Jones, S.A., Moore, L.B., Shenk, J.L., Wisely, G.B., Hamilton, G.A., McKee, D.D., Tomkinson, N.C., LeCluyse, E.L., Lambert, M.H., and Willson, T.M. (2000). The pregnane X receptor: a promiscuous xenobiotic receptor that has diverged during evolution. Molecular endocrinology 14, 27-39.
Juliano, R.L., and Ling, V. (1976). A surface glycoprotein modulating drug permeability in Chinese hamster ovary cell mutants. Biochimica et Biophysica Acta (BBA)-Biomembranes 455, 152-162.
Kast, H.R., Goodwin, B., Tarr, P.T., Jones, S.A., Anisfeld, A.M., Stoltz, C.M., Tontonoz, P., Kliewer, S., Willson, T.M., and Edwards, P.A. (2002). Regulation of multidrug resistance-associated protein 2 (ABCC2) by the nuclear receptors pregnane X receptor, farnesoid X-activated receptor, and constitutive androstane receptor. Journal of Biological Chemistry 277, 2908-2915.
King, C., Tang, W., Ngui, J., Tephly, T., and Braun, M. (2001). Characterization of rat and human UDP-glucuronosyltransferases responsible for the in vitro glucuronidation of diclofenac. Toxicological Sciences 61, 49-53.
Kliewer, S.A., Goodwin, B., and Willson, T.M. (2002). The nuclear pregnane X receptor: a key regulator of xenobiotic metabolism. Endocrine reviews 23, 687-702.
Kobayashi, M., and Yamamoto, M. (2005). Molecular mechanisms activating the Nrf2-Keap1 pathway of antioxidant gene regulation. Antioxidants & redox signaling 7, 385-394.
Kondraganti, S.R., Jiang, W., Jaiswal, A.K., and Moorthy, B. (2008). Persistent induction of hepatic and pulmonary phase II enzymes by 3-methylcholanthrene in rats. Toxicological sciences 102, 337-344.
Kool, M., Van Der Linden, M., de Haas, M., Scheffer, G.L., De Vree, J.M.L., Smith, A.J., Jansen, G., Peters, G.J., Ponne, N., and Scheper, R.J. (1999). MRP3, an organic anion transporter able to transport anti-cancer drugs. Proceedings of the National Academy of Sciences 96, 6914-6919.
Krithika, R., Verma, R., and Shrivastav, P. (2013). Antioxidative and cytoprotective effects of andrographolide against CCl4-induced hepatotoxicity in HepG2 cells. Human & experimental toxicology 32, 530-543.
Kruh, G.D., and Belinsky, M.G. (2003). The MRP family of drug efflux pumps. Oncogene 22, 7537-7552.
Lee, M.-J., Rao, Y.K., Chen, K., Lee, Y.-C., Chung, Y.-S., and Tzeng, Y.-M. (2010). Andrographolide and 14-deoxy-11, 12-didehydroandrographolide from Andrographis paniculata attenuate high glucose-induced fibrosis and apoptosis in murine renal mesangeal cell lines. Journal of ethnopharmacology 132, 497-505.
Leier, I., JEDLITSCHKY, G., BUCHHOLZ, U., CENTER, M., Susan, P., DEELEY, R.G., and KEPPLER, D. (1996). ATP-dependent glutathione disulphide transport mediated by the MRP gene-encoded conjugate export pump. Biochemical Journal 314, 433-437.
Leslie, E.M., Deeley, R.G., and Cole, S.P. (2005). Multidrug resistance proteins: role of P-glycoprotein, MRP1, MRP2, and BCRP (ABCG2) in tissue defense. Toxicology and applied pharmacology 204, 216-237.
Lichti-Kaiser, K., and Staudinger, J.L. (2008). The traditional Chinese herbal remedy tian xian activates pregnane X receptor and induces CYP3A gene expression in hepatocytes. Drug Metabolism and Disposition 36, 1538-1545.
Lii, C.-K., Tsai, C.-W., and Wu, C.-C. (2006). Garlic allyl sulfides display differential modulation of rat cytochrome P450 2B1 and the placental form glutathione S-transferase in various organs. Journal of agricultural and food chemistry 54, 5191-5196.
Lim, J.C.W., Chan, T.K., Ng, D.S., Sagineedu, S.R., Stanslas, J., and Wong, W. (2012). Andrographolide and its analogues: versatile bioactive molecules for combating inflammation and cancer. Clinical and Experimental Pharmacology and Physiology 39, 300-310.
Liska, D.J. (1998). The detoxification enzyme systems. Altern Med Rev 3, 187-198.
Maglich, J.M., Stoltz, C.M., Goodwin, B., Hawkins-Brown, D., Moore, J.T., and Kliewer, S.A. (2002). Nuclear pregnane x receptor and constitutive androstane receptor regulate overlapping but distinct sets of genes involved in xenobiotic detoxification. Molecular pharmacology 62, 638-646.
Meier, P.J., Eckhardt, U., Schroeder, A., Hagenbuch, B., and Stieger, B. (1997). Substrate specificity of sinusoidal bile acid and organic anion uptake systems in rat and human liver. Hepatology 26, 1667-1677.
Meyer, U.A. (1996). Overview of enzymes of drug metabolism. Journal of pharmacokinetics and biopharmaceutics 24, 449-459.
Minsavage, G.D., Park, S.-k., and Gasiewicz, T.A. (2004). The aryl hydrocarbon receptor (AhR) tyrosine 9, a residue that is essential for AhR DNA binding activity, is not a phosphoresidue but augments AhR phosphorylation. Journal of Biological Chemistry 279, 20582-20593.
Moon, Y.J., Wang, X., and Morris, M.E. (2006). Dietary flavonoids: effects on xenobiotic and carcinogen metabolism. Toxicology in vitro 20, 187-210.
Moore, L.B., Goodwin, B., Jones, S.A., Wisely, G.B., Serabjit-Singh, C.J., Willson, T.M., Collins, J.L., and Kliewer, S.A. (2000). St. John''s wort induces hepatic drug metabolism through activation of the pregnane X receptor. Proceedings of the National Academy of Sciences 97, 7500-7502.
Morel, F., Rauch, C., Petit, E., Piton, A., Theret, N., Coles, B., and Guillouzo, A. (2004). Gene and protein characterization of the human glutathione S-transferase kappa and evidence for a peroxisomal localization. Journal of Biological Chemistry 279, 16246-16253.
Nebert, D.W., ADESNIK, M., COON, M.J., ESTABROOK, R.W., GONZALEZ, F.J., GUENGERICH, F.P., GUNSALUS, I.C., JOHNSON, E.F., KEMPER, B., and LEVIN, W. (1987). The P450 gene superfamily: recommended nomenclature. DNA 6, 1-11.
Nebert, D.W., and Dalton, T.P. (2006). The role of cytochrome P450 enzymes in endogenous signalling pathways and environmental carcinogenesis. Nature Reviews Cancer 6, 947-960.
Niranjan Reddy, V., Malla Reddy, S., Ravikanth, V., Krishnaiah, P., Venkateshwar Goud, T., Rao, T., Siva Ram, T., Gonnade, R.G., Bhadbhade, M., and Venkateswarlu, Y. (2005). A new bis-andrographolide ether from Andrographis paniculata nees and evaluation of anti-HIV activity. Natural product research 19, 223-230.
Ooi, J.P., Kuroyanagi, M., Sulaiman, S.F., Muhammad, T.S.T., and Tan, M.L. (2011). Andrographolide and 14-deoxy-11, 12-didehydroandrographolide inhibit cytochrome P450s in HepG2 hepatoma cells. Life sciences 88, 447-454.
Parichatikanond, W., Suthisisang, C., Dhepakson, P., and Herunsalee, A. (2010). Study of anti-inflammatory activities of the pure compounds from Andrographis paniculata (burm. f.) Nees and their effects on gene expression. International immunopharmacology 10, 1361-1373.
Parker, R.S., Sontag, T.J., and Swanson, J.E. (2000). Cytochrome P4503A-dependent metabolism of tocopherols and inhibition by sesamin. Biochemical and biophysical research communications 277, 531-534.
Pavek, P., and Dvorak, Z. (2008). Xenobiotic-induced transcriptional regulation of xenobiotic metabolizing enzymes of the cytochrome P450 superfamily in human extrahepatic tissues. Current drug metabolism 9, 129-143.
Pholphana, N., Rangkadilok, N., Thongnest, S., Ruchirawat, S., Ruchirawat, M., and Satayavivad, J. (2004). Determination and variation of three active diterpenoids in Andrographis paniculata (Burm. f.) Nees. Phytochemical Analysis 15, 365-371.
Pikuleva, I.A. (2006). Cholesterol-metabolizing cytochromes P450. Drug metabolism and disposition 34, 513-520.
Pitot, H., Dragan, Y., Sargent, L., and Xu, Y. (1991). Biochemical markers associated with the stages of promotion and progression during hepatocarcinogenesis in the rat. Environmental health perspectives 93, 181.
Radhika, P., Prasad, Y.R., and Sowjanya, K. (2012). A new diterpene from the leaves of Andrographis paniculata Nees. Natural product communications 7, 485-486.
Rao, Y.K., Vimalamma, G., Rao, C.V., and Tzeng, Y.-M. (2004). Flavonoids and andrographolides from Andrographis paniculata. Phytochemistry 65, 2317-2321.
Ritter, J.K. (2000). Roles of glucuronidation and UDP-glucuronosyltransferases in xenobiotic bioactivation reactions. Chemico-biological interactions 129, 171-193.
Rojo, A.I., Sagarra, M.R.d., and Cuadrado, A. (2008). GSK??3β down?鬳egulates the transcription factor Nrf2 after oxidant damage: relevance to exposure of neuronal cells to oxidative stress. Journal of neurochemistry 105, 192-202.
Rowland, A., Miners, J.O., and Mackenzie, P.I. (2013). The UDP-glucuronosyltransferases: their role in drug metabolism and detoxification. The international journal of biochemistry & cell biology 45, 1121-1132.
Sakaki, T., Kagawa, N., Yamamoto, K., and Inouye, K. (2005). Metabolism of vitamin D3 by cytochromes P450. Frontiers in bioscience : a journal and virtual library 10.
Satoh, K., Kitahara, A., Soma, Y., Inaba, Y., Hatayama, I., and Sato, K. (1985). Purification, induction, and distribution of placental glutathione transferase: a new marker enzyme for preneoplastic cells in the rat chemical hepatocarcinogenesis. Proceedings of the National Academy of Sciences 82, 3964-3968.
Shen, G., and Kong, A.N. (2009). Nrf2 plays an important role in coordinated regulation of Phase II drug metabolism enzymes and Phase III drug transporters. Biopharmaceutics & drug disposition 30, 345-355.
Shia, C.-S., Juang, S.-H., Tsai, S.-Y., Lee Chao, P.-D., and Hou, Y.-C. (2013). Interaction of rhubarb and methotrexate in rats: in vivo and ex vivo approaches. The American journal of Chinese medicine 41, 1427-1438.
Siegel, D., Gustafson, D.L., Dehn, D.L., Han, J.Y., Boonchoong, P., Berliner, L.J., and Ross, D. (2004). NAD (P) H: quinone oxidoreductase 1: role as a superoxide scavenger. Molecular pharmacology 65, 1238-1247.
Singha, P.K., Roy, S., and Dey, S. (2007). Protective activity of andrographolide and arabinogalactan proteins from Andrographis paniculata Nees. against ethanol-induced toxicity in mice. Journal of ethnopharmacology 111, 13-21.
Soyalan, B., Minn, J., Schmitz, H.J., Schrenk, D., Will, F., Dietrich, H., Baum, M., Eisenbrand, G., and Janzowski, C. (2011). Apple juice intervention modulates expression of ARE-dependent genes in rat colon and liver. European journal of nutrition 50, 135-143.
Sun, Z., Huang, Z., and Zhang, D.D. (2009). Phosphorylation of Nrf2 at multiple sites by MAP kinases has a limited contribution in modulating the Nrf2-dependent antioxidant response. PloS one 4, e6588.
Surh, Y.-J., Kundu, J.K., and Na, H.-K. (2008). Nrf2 as a master redox switch in turning on the cellular signaling involved in the induction of cytoprotective genes by some chemopreventive phytochemicals. Planta medica 74, 1526-1539.
Taguchi, K., Motohashi, H., and Yamamoto, M. (2011). Molecular mechanisms of the Keap1–Nrf2 pathway in stress response and cancer evolution. Genes to Cells 16, 123-140.
Tamai, I., Nezu, J.-i., Uchino, H., Sai, Y., Oku, A., Shimane, M., and Tsuji, A. (2000). Molecular identification and characterization of novel members of the human organic anion transporter (OATP) family. Biochemical and biophysical research communications 273, 251-260.
Thisoda, P., Rangkadilok, N., Pholphana, N., Worasuttayangkurn, L., Ruchirawat, S., and Satayavivad, J. (2006). Inhibitory effect of Andrographis paniculata extract and its active diterpenoids on platelet aggregation. European journal of pharmacology 553, 39-45.
Timsit, Y.E., and Negishi, M. (2007). CAR and PXR: the xenobiotic-sensing receptors. Steroids 72, 231-246.
Tsai, C.-W., Yang, J.-J., Chen, H.-W., Sheen, L.-Y., and Lii, C.-K. (2005). Garlic organosulfur compounds upregulate the expression of the π class of glutathione S-transferase in rat primary hepatocytes. The Journal of nutrition 135, 2560-2565.
Tukey, R.H., and Strassburg, C.P. (2000). Human UDP-glucuronosyltransferases: metabolism, expression, and disease. Annual review of pharmacology and toxicology 40, 581-616.
van Iersel, M.L., Verhagen, H., and van Bladeren, P.J. (1999). The role of biotransformation in dietary (anti) carcinogenesis. Mutation Research/Genetic Toxicology and Environmental Mutagenesis 443, 259-270.
Vasiliou, V., Ross, D., and Nebert, D.W. (2006). Update of the NAD (P) H: quinone oxidoreductase (NQO) gene family. Human genomics 2, 1.
Wang, H., and LeCluyse, E.L. (2003). Role of orphan nuclear receptors in the regulation of drug-metabolising enzymes. Clinical pharmacokinetics 42, 1331-1357.
Wauthier, V., Verbeeck, R.-K., and Buc Calderon, P. (2007). The effect of ageing on cytochrome p450 enzymes: consequences for drug biotransformation in the elderly. Current medicinal chemistry 14, 745-757.
Wei, P., Zhang, J., Dowhan, D., Han, Y., and Moore, D. (2002). Specific and overlapping functions of the nuclear hormone receptors CAR and PXR in xenobiotic response. The pharmacogenomics journal 2, 117-126.
WHO (2002). WHO traditional medicine strategy 2002-2005.
Wu, C.-C., Sheen, L.-Y., Chen, H.-W., Kuo, W.-W., Tsai, S.-J., and Lii, C.-K. (2002). Differential effects of garlic oil and its three major organosulfur components on the hepatic detoxification system in rats. Journal of agricultural and food chemistry 50, 378-383.
Xu, C., Li, C.Y.-T., and Kong, A.-N.T. (2005). Induction of phase I, II and III drug metabolism/transport by xenobiotics. Archives of pharmacal research 28, 249-268.
Yang, C.S., Chhabra, S.K., Hong, J.-Y., and Smith, T.J. (2001). Mechanisms of inhibition of chemical toxicity and carcinogenesis by diallyl sulfide (DAS) and related compounds from garlic. The Journal of nutrition 131, 1041S-1045S.
Yeung, E.Y., Sueyoshi, T., Negishi, M., and Chang, T.K. (2008). Identification of Ginkgo biloba as a novel activator of pregnane X receptor. Drug Metabolism and Disposition 36, 2270-2276.
Yoopan, N., Thisoda, P., Rangkadilok, N., Sahasitiwat, S., Pholphana, N., Ruchirawat, S., and Satayavivad, J. (2007). Cardiovascular effects of 14-deoxy-11, 12-didehydroandrographolide and Andrographis paniculata extracts. Planta medica 73, 503-511.
Yu, C., Hsieh, Y., Lin, S., Chi, Y., Hariharan, P., Chao, P., and Hou, Y. (2014). Potential modulation on P-glycoprotein and CYP3A by soymilk and miso: in vivo and ex-vivo studies. Food chemistry 149, 25-30.
Zhang, C., KUROYANGI, M., and TAN, B.K. (1998). Cardiovascular activity of 14-deoxy-11, 12-didehydroandrographolide in the anaesthetised rat and isolated right atria. Pharmacological research 38, 413-418.
Zhang, C., and Tan, B. (1999). Effects of 14?駤eoxyandrographolide and 14?駤eoxy??11, 12?駤idehydroandrographolide on nitric oxide production in cultured human endothelial cells. Phytotherapy Research 13, 157-159.
Zhang, D.D., Lo, S.-C., Cross, J.V., Templeton, D.J., and Hannink, M. (2004). Keap1 is a redox-regulated substrate adaptor protein for a Cul3-dependent ubiquitin ligase complex. Molecular and cellular biology 24, 10941-10953.
Zhang, D.D., Lo, S.-C., Sun, Z., Habib, G.M., Lieberman, M.W., and Hannink, M. (2005). Ubiquitination of Keap1, a BTB-Kelch substrate adaptor protein for Cul3, targets Keap1 for degradation by a proteasome-independent pathway. Journal of Biological Chemistry 280, 30091-30099.



QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top
無相關期刊