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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 陳水田(Shui-Tein Chen) | |
| dc.contributor.author | Ming-Hui Chen | en |
| dc.contributor.author | 陳明輝 | zh_TW |
| dc.date.accessioned | 2021-06-08T02:23:51Z | - |
| dc.date.copyright | 2015-08-25 | |
| dc.date.issued | 2015 | |
| dc.date.submitted | 2015-08-18 | |
| dc.identifier.citation | 1 Zhao, L. et al. Berberine reduces insulin resistance induced by dexamethasone in theca cells in vitro. Fertility and sterility 95, 461-463, doi:10.1016/j.fertnstert.2010.07.1090 (2011).
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Evidence-based complementary and alternative medicine : eCAM 2014, 289264, doi:10.1155/2014/289264 (2014). 7 Correche, E. R. et al. Antioxidant and cytotoxic activities of canadine: biological effects and structural aspects. Bioorganic & medicinal chemistry 16, 3641-3651, doi:10.1016/j.bmc.2008.02.015 (2008). 8 Vrzal, R. et al. Activation of the aryl hydrocarbon receptor by berberine in HepG2 and H4IIE cells: Biphasic effect on CYP1A1. Biochemical pharmacology 70, 925-936, doi:10.1016/j.bcp.2005.06.016 (2005). 9 Wang, Y. et al. Comprehensive study in the inhibitory effect of berberine on gene transcription, including TATA box. PloS one 6, e23495, doi:10.1371/journal.pone.0023495 (2011). 10 Kim, S. H. et al. Berberine Activates GLUT1-Mediated Glucose Uptake in 3T3-L1 Adipocytes. Biological and Pharmaceutical Bulletin 30, 2120-2125, doi:10.1248/bpb.30.2120 (2007). 11 Yin, J., Ye, J. & Jia, W. Effects and mechanisms of berberine in diabetes treatment. Acta Pharmaceutica Sinica B 2, 327-334, doi:http://dx.doi.org/10.1016/j.apsb.2012.06.003 (2012). 12 Cok, A. et al. Berberine acutely activates the glucose transport activity of GLUT1. Biochimie 93, 1187-1192, doi:http://dx.doi.org/10.1016/j.biochi.2011.04.013 (2011). 13 Pang, B. et al. Application of Berberine on Treating Type 2 Diabetes Mellitus. International Journal of Endocrinology 2015, 12, doi:10.1155/2015/905749 (2015). 14 Sha, W. et al. An Ancient Chinese Herb Berberine; New Research in Diabetes Mellitus. International Journal of Integrative Medicine 1, 1, doi:10.5772/56950 (2013). 15 Hayes, J. D., Dinkova-Kostova, A. T. & McMahon, M. Cross-talk between transcription factors AhR and Nrf2: lessons for cancer chemoprevention from dioxin. Toxicological sciences : an official journal of the Society of Toxicology 111, 199-201, doi:10.1093/toxsci/kfp168 (2009). 16 Tsuji, G. et al. Identification of ketoconazole as an AhR-Nrf2 activator in cultured human keratinocytes: the basis of its anti-inflammatory effect. The Journal of investigative dermatology 132, 59-68, doi:10.1038/jid.2011.194 (2012). 17 Murray, I. A., Patterson, A. D. & Perdew, G. H. Aryl hydrocarbon receptor ligands in cancer: friend and foe. Nature Reviews Cancer 14, 801-814, doi:10.1038/nrc3846 (2014). 18 Tanos, R. et al. Aryl hydrocarbon receptor regulates the cholesterol biosynthetic pathway in a dioxin response element-independent manner. Hepatology 55, 1994-2004, doi:10.1002/hep.25571 (2012). 19 Barouki, R., Coumoul, X. & Fernandez-Salguero, P. M. The aryl hydrocarbon receptor, more than a xenobiotic-interacting protein. FEBS Letters 581, 3608-3615, doi:http://dx.doi.org/10.1016/j.febslet.2007.03.046 (2007). 20 Chirulli, V. et al. Inducibility of AhR-regulated CYP genes by beta-naphthoflavone in the liver, lung, kidney and heart of the pig. Toxicology 240, 25-37, doi:10.1016/j.tox.2007.07.015 (2007). 21 Goryo, K. et al. Identification of amino acid residues in the Ah receptor involved in ligand binding. Biochemical and biophysical research communications 354, 396-402, doi:10.1016/j.bbrc.2006.12.227 (2007). 22 Ovando, B. J., Vezina, C. M., McGarrigle, B. P. & Olson, J. R. Hepatic gene downregulation following acute and subchronic exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin. Toxicological sciences : an official journal of the Society of Toxicology 94, 428-438, doi:10.1093/toxsci/kfl111 (2006). 23 Rico de Souza, A. et al. Genetic ablation of the aryl hydrocarbon receptor causes cigarette smoke-induced mitochondrial dysfunction and apoptosis. The Journal of biological chemistry 286, 43214-43228, doi:10.1074/jbc.M111.258764 (2011). 24 Vrzal, R. et al. Dexamethasone controls aryl hydrocarbon receptor (AhR)-mediated CYP1A1 and CYP1A2 expression and activity in primary cultures of human hepatocytes. Chemico-biological interactions 179, 288-296, doi:10.1016/j.cbi.2008.10.035 (2009). 25 Nannelli, A. et al. Effect of beta-naphthoflavone on AhR-regulated genes (CYP1A1, 1A2, 1B1, 2S1, Nrf2, and GST) and antioxidant enzymes in various brain regions of pig. Toxicology 265, 69-79, doi:10.1016/j.tox.2009.09.010 (2009). 26 Wang, C., Xu, C. X., Bu, Y., Bottum, K. M. & Tischkau, S. A. Beta-naphthoflavone (DB06732) mediates estrogen receptor-positive breast cancer cell cycle arrest through AhR-dependent regulation of PI3K/AKT and MAPK/ERK signaling. Carcinogenesis 35, 703-713, doi:10.1093/carcin/bgt356 (2014). 27 Shi, L. Z. & Czuprynski, C. J. Beta-naphthoflavone causes an AhR-independent inhibition of invasion and intracellular multiplication of Listeria monocytogenes in murine hepatocytes. Microbial pathogenesis 47, 258-266, doi:10.1016/j.micpath.2009.08.004 (2009). 28 He, J. et al. Activation of the aryl hydrocarbon receptor sensitizes mice to nonalcoholic steatohepatitis by deactivating mitochondrial sirtuin deacetylase Sirt3. Molecular and cellular biology 33, 2047-2055, doi:10.1128/MCB.01658-12 (2013). 29 Quintana, F. J. The aryl hydrocarbon receptor: a molecular pathway for the environmental control of the immune response. Immunology 138, 183-189, doi:10.1111/imm.12046 (2013). 30 Beischlag, T. V., Morales, J. L., Hollingshead, B. D. & Perdew, G. H. The Aryl Hydrocarbon Receptor Complex and the Control of Gene Expression. Critical reviews in eukaryotic gene expression 18, 207-250 (2008). 31 Thorens, B. & Mueckler, M. Glucose transporters in the 21st Century. American Journal of Physiology - Endocrinology and Metabolism 298, E141-E145, doi:10.1152/ajpendo.00712.2009 (2010). 32 Mueckler, M. & Thorens, B. The SLC2 (GLUT) Family of Membrane Transporters. Molecular aspects of medicine 34, 121-138, doi:10.1016/j.mam.2012.07.001 (2013). 33 Thorens, B., Wu, Y. J., Leahy, J. L. & Weir, G. C. The loss of GLUT2 expression by glucose-unresponsive beta cells of db/db mice is reversible and is induced by the diabetic environment. Journal of Clinical Investigation 90, 77-85 (1992). 34 Karnieli, E. & Armoni, M. Transcriptional regulation of the insulin-responsive glucose transporter GLUT4 gene: from physiology to pathology. American Journal of Physiology - Endocrinology and Metabolism 295, E38-E45 (2008). 35 Lacombe, V. A. Expression and Regulation of Facilitative Glucose Transporters in Equine Insulin-Sensitive Tissue: From Physiology to Pathology. ISRN Veterinary Science 2014, 409547, doi:10.1155/2014/409547 (2014). 36 Kim, H. S. et al. Berberine-induced AMPK activation inhibits the metastatic potential of melanoma cells via reduction of ERK activity and COX-2 protein expression. Biochemical pharmacology 83, 385-394, doi:10.1016/j.bcp.2011.11.008 (2012). 37 Hu, H.-y. et al. Set9, NF-[kappa]B, and microRNA-21 mediate berberine-induced apoptosis of human multiple myeloma cells. Acta pharmacologica Sinica 34, 157-166 (2013). | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/19864 | - |
| dc.description.abstract | 隨著高通量快篩技術不斷推陳出新，從中草藥篩選出先導化合物已成常規，然而許多分子，雖然具有生物活性，但礙於訊號傳遞與分子層面的機轉十分複雜，使中藥分子的基礎研究進展較緩慢。
本研究主旨為探討一種異喹琳衍生物─坎那定(Canadine, CND)的化學性質與生物活性，首先將小蘗鹼(Berberine, BBR)進行還原反應，經過純化後得到CND並以核磁共振與質譜確保其純度，同時也觀察其顏色變化造成光譜性質的改變，接著，測量CND對不同細胞株毒性，由數據可得知CND的毒性明顯地較BBR低。使用CND進行體外實驗分析其生物活性，發現其能降低HepG2細胞內的ROS含量並能活化AhR，使AhR其進入細胞核內作為轉錄因子，另一方面，也發現CND能上調HL–60細胞中GLUT6的mRNA與蛋白質之表現量，進而增加其對環境中葡萄糖的攝取，但於PBMC細胞卻無此現象。此研究成果，不僅利於爾後新藥開發與藥物治療等相關研究，也對於GLUT6有更進一步的認識。 | zh_TW |
| dc.description.provenance | Made available in DSpace on 2021-06-08T02:23:51Z (GMT). No. of bitstreams: 1 ntu-104-R02b46025-1.pdf: 1960638 bytes, checksum: 408b93d71732c7f387cf919be53f81d2 (MD5) Previous issue date: 2015 | en |
| dc.description.tableofcontents | 口試委員會審定書........................................... i
誌謝..................................................... ii 英文縮寫表.................................... .......... iii 中文摘要................................................. iv 英文摘要.................................................. v 第一章 緒論............................................... 1 1.1前言................................................... 1 1.2異喹琳衍生物之藥理活性 ……………………………………….…...... 1 1.3芳香烴受體………………………………………………………………. 1 1.4葡萄糖轉運蛋白…………………………………………………………. 2 1.5坎那定之性質研究………………………………………………………. 3 第二章 材料與方法………………………………………………………….... 4 2.1 CND的製備……………………………………………………………… 4 2.2 CND之性質分析……………………………………………………….... 4 2.2.1薄層層析………………………………………………………….... 4 2.2.2紫外光-可見光譜…………………………………………………... 4 2.2.3 1H與13C核磁共振………………………………………………… 4 2.2.4 LC/MS……………………………………………………….……… 5 2.3細胞株來源與培養………………………………………………………... 5 2.4細胞繼代培養 ……………………………………………………………. 5 2.5細胞毒性試驗……………………………………………………………... 5 2.6共軛焦顯微鏡……………………………………………………………... 6 2.7細胞內活性氧檢測………………………………………………………... 6 2.8 GLUT基因表現分析…………………………………………………....… 7 2.9葡萄糖攝取試驗…………………………………………………………... 7 第三章 結果與討論………………………………………………………………… 8 3.1 CND的合成與定性………………………………………………………… 8 3.1.1 CND之薄層分析…………………………………………………… 8 3.1.2 CND之吸收光譜分析……………………………………………… 8 3.1.3以核磁共振對CND作結構分析…………………………………... 8 3.1.4以LC/MS確認CND分子量與純度………………………………. 8 3.2 CND之相對於BBR有較低的細胞毒性………………………………… 9 3.3 CND能於HepG2中活化AhR並增加ROS之清除能力……………...… 9 3.4 CND藉由上調GLUT6以增加HL-60對葡萄糖的攝取量 ………...……. 9 第四章 總論……………………………………………………………………… 11 第五章 圖片與表格………………………………………….………………...… 12 圖目錄 圖1. 研究目的示意圖…………………………..…………………………………. 12 圖2. CND之合成反應示意圖……………….………………………………….... 12 圖3. 利用TLC檢測對CND進行純度檢測………..…….…………………….. 13 圖4. BBR與CND的吸收光譜特性…………………………………………….. 13 圖5. CND之1H NMR圖譜…………………………..………………………… 14 圖6. CND之13C NMR圖譜……………..…………………………………….. 15 圖7. LC/MS的分析結果………………….……………………………………… 16 圖8. CND對HepG2胞內ROS造成的影響…………………………………… 19 圖9. CND影響HepG2中AhR的位置…………………………………………. 20 圖10. CND於不同時間點對GLUT6基因表現量的影響……………………… 22 圖11. CND對於HL-60中GLUT6蛋白質表現量之影響…………………...… 23 圖12. CND影響HL-60對葡萄糖的攝取……………………………………….. 24 表目錄 表1. BBR與CNR對不同細胞株的細胞毒性…………………..………………. 18 表2. CND對HL-60中GLUT家族mRNA表現量之影響……….……...…….. 21 參考文獻…………………………………………………………………………… 25 附錄……………………………………………………………………….……….. 29 附錄表1…………………………………………………………………….……… 29 附錄圖1…….…..……………………………………………………….….……… 29 附錄圖2……………………………………………………………….…….……… 30 附錄圖3………………………………………………………….………………… 30 | |
| dc.language.iso | zh-TW | |
| dc.title | 坎那定之生物功能探討 | zh_TW |
| dc.title | Investigation of Biological Effects of Canadine | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 103-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 謝榮(Jung-Feng Hsieh),張明奎(Ming-Kuei Jang) | |
| dc.subject.keyword | 小蘗鹼,坎那定,抗氧化,芳香烴受體,葡萄糖轉運蛋白, | zh_TW |
| dc.subject.keyword | Berberine,Canadine,Antioxidant,Aryl hydrocarbon receptor,Glucose transporter, | en |
| dc.relation.page | 30 | |
| dc.rights.note | 未授權 | |
| dc.date.accepted | 2015-08-19 | |
| dc.contributor.author-college | 生命科學院 | zh_TW |
| dc.contributor.author-dept | 生化科學研究所 | zh_TW |
| 顯示於系所單位： | 生化科學研究所 | |
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