跳到主要內容

臺灣博碩士論文加值系統

(3.231.230.177) 您好!臺灣時間:2021/08/04 05:30
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:吳宜潔
研究生(外文):Yi-Chieh Wu
論文名稱:中藥黃芩與化合物Wogonin在人類肝癌細胞中對B型肝炎病毒抑制的機轉
論文名稱(外文):Mechanistic study of anti-human hepatitis B virus activity of Scutellaria radix & Wogonin in human hepatoma cells
指導教授:葉小帆葉小帆引用關係
指導教授(外文):Sheau-Farn Yeh
學位類別:碩士
校院名稱:國立陽明大學
系所名稱:生化暨分子生物研究所
學門:生命科學學門
學類:生物化學學類
論文種類:學術論文
論文出版年:2009
畢業學年度:97
語文別:中文
論文頁數:85
中文關鍵詞:黃芩B型肝炎病毒
外文關鍵詞:WogoninScutellaria radixHBV
相關次數:
  • 被引用被引用:0
  • 點閱點閱:132
  • 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:1
B型肝炎病毒的感染會造成急性甚至慢性肝炎的發生,而慢性肝炎的患者具有罹患肝硬化或是肝癌的高度風險。目前雖然已經有B型肝炎疫苗的注射以預防,但對於帶原者卻沒有很好的治療方式,開發有效的治療B型肝炎藥物仍是迫切需要的研究。中藥小柴胡湯在過去常被用於治療肝病,柴胡以及黃芩為其中兩種主要成份,在篩選抑制B型肝炎病毒表面抗原的產生時,發現小柴胡湯中的黃芩具有良好的活性。本論文主要探討黃芩以及其中的一種化合物 Wogonin 抑制B型肝炎病毒的作用機制。在人類肝癌細胞中,黃芩與 Wogonin 除了可以抑制B型肝炎病毒表面抗原的產生,尚可減少B型肝炎病毒複製的中間產物RNA及病毒顆粒。為了瞭解黃芩和Wogonin 對B型肝炎病毒基因表現的作用機制,利用 Luciferase reporter assay 分析B型肝炎病毒主要的四個啟動子在肝癌細胞中的活性,實驗的結果明確看到黃芩和 Wogonin 都會明顯的抑制核心抗原的活性,而當外送核心抗原啟動子到腎臟上皮癌細胞293T 時,藥物對啟動子的抑制現象則消失,此結果表示黃芩和 Wogonin 對於核心抗原啟動子的抑制是具有肝組織特異性的。當外送一些肝組織特有或是肝組織特多的轉錄因子到人類肝癌細胞時,可以看到當PGC-1�悀j量表現時,黃芩對核心抗原啟動子的抑制效果減弱 ; 而當 CEBP/�恁BPPAR�� 大量表現時,Wogonin 對核心抗原啟動子的抑制效果減弱, Wogonin 與黃芩均具有抗B型肝炎病毒的效果,黃芩與 Wogonin 可能是透過不同的機轉抑制B型肝炎病毒的基因表現及複製,黃芩中還有其他有效成份值得進一步探討。
Hepatitis B virus (HBV) infection causes acute and chronic hepatitis, and the affected patients have an increased risk of developing liver cirrhosis and hepatocellular carcinoma (HCC). Although a preventive vaccine for HBV is
available, effective drugs to eradicate HBV in chronic carriers are still urgently needed.The Chinese herbal medicine Xiao-Chai-Hu-Tang consists of Bupleuri radix and Scutellaria radix (HD-1S) and is widely used for treatment of liver disease. In searching of compounds on suppression of hepatitis B surface antigen (HBsAg) production, our laboratory previously have shown that HD-1S strongly suppressed hepatitis B surface antigen (HBsAg) in human hepatoma cells. In this study, I demonstrated that the aqueous extract of HD-1S and one of its components Wogonin had potent anti-HBV activity. Both HD-1S and Wogonin not only suppressed HBsAg production but also decreased HBV transcripts and HBV viral particles in cultured human hepatoma cells. To understand the molecular mechanism of suppression of HBV gene expression by HD-1S and Wogonin, the effects of HD-1S and Wogonin on four viral promoter activities using luciferase as a reporter were examined. This study showed clearly that both HD-1S and Wogonin selectively suppresses core promoter (CP) of HBV. Such suppressive effects of HD-1S and Wogonin are liver-specific because no suppressive activity of HD-1S and Wogonin was observed when CP activity was assayed in non-liver 293T cells. Furthermore, ectopic expression of PGC-1�� and PPARr/CEBP�� abolished the suppressive effect of HD-1S and Wogonin on HBV CP activity, respectively. Therefore, HD-1S and Wogonin may selectively modulate transcriptional machinery of human liver cells to suppress HBV gene expression and replication. Results from this study also suggested that some components other than Wogonin might also have novel anti-HBV activity and deserve futher
investigation in the future.
中文摘要…………………………………………………………………1
英文摘要…………………………………………………………………2~3
緒論………………………………………………………………………4~12
材料與方法………………………………………………………………13~29
結果………………………………………………………………………30~39
討論………………………………………………………………………40~44
參考文獻…………………………………………………………………45~50
圖表………………………………………………………………………51~79
Allen MI., Deslauriers M., Andrews CW., Tripples GA., Walters K-A., Tyrrell DLJ., Brown N., Condreay LD., 1998. Identification and characterization of mutation in hepatitis B virus resistant to lamivudine. Hepatology 27 : 1670-1677.
Chang WH., Chen CH., Lu FJ., 2002. Different effects of baicalein, baicalin and wogonin on mitochondrial function, glutathione content and cell cycle progression in human hepatoma cell lines. Planta Med. 68:128-132.
Chen LG., Hung LY., Tsai KW., Pan YS., Tsai YD., Li YZ., Liu YW., 2008.
Wogonin, a bioactive flavonoid in herbal tea, inhibits inflammatory cyclooxygenase-2 gene expression in human lung epithelial cancer cells. Mol Nutr Food Res. 52:1349-1357.
Chi YS., Lim H., Park H., Kim HP., 2003. Effects of wogonin, a plant flavone from Scutellaria radix, on skin inflammation: in vivo regulation of inflammation-associated gene expression. Biochem Pharmacol. 66:1271-1278.
Cho H., Yun CW., Park WK., Kong JY., Kim KS., Park Y., Lee S., Kim BK., 2004. Modulation of the activity of pro-inflammatory enzymes, COX-2 and iNOS, by chrysin derivatives. Pharmacol Res. 49:37-43.
Cho J., Lee HK., 2004. Wogonin inhibits excitotoxic and oxidative neuronal damage in primary cultured rat cortical cells. Eur J Pharmacol. 485:105-110.
Chen X., Nishida H., Konishi T., 2003. Baicalin promoted the repair of DNA single strand breakage caused by H2O2 in cultured NIH3T3 fibroblasts. Biol Pharm Bull. 26:282-284.
Dan DS., Cameron CH., Briggs M., 1975. Virus-like particles in serum of patients with Australia-antigen-associated hepatitis. Lancet 1 : 695-698.
Dane DS., Cameron CH., Briggs M., 1970. Virus-like particles in serum of patients with Australia-antigen-associated hepatitis. Lancet. 1 : 695-698.
De Clercq E., 1999. Perspectives for the treatment of hepatitis B virus infections. Int J Antimicrob Agents 12, 81-95.
Doitsh G., Shaul Y., 2004. Enhancer I predominance in hepatitis B virus gene expression. Mol Cell Biol 24 : 1799-1808.
Edgington, T.S., Chisari, F.V., 1975. Immunological aspects of hepatitis B virus infection. Am J Med Sci 270 : 212-227.
Ganem D., Pollack JR., Tavis J., 2004. Hepatitis B virus reverse transcriptase and its many roles in hepadnaviral genomic replication. Infect Agents Dis 3 : 85-93.
Ganem D., Prince AM., 2004., Hepatitis B virus infection--natural history and clinical consequences. N EnglJ Med 350 : 1118-1129.
Gao Z., Huang K., Yang X., Xu H., 1999. Free radical scavenging and antioxidant activities of flavonoids extracted from the radix of Scutellaria baicalensis Georgi. Biochim Biophys Acta. 1472:643-650.
Gao Z., Huang K., Xu H., 2001. Protective effects of flavonoids in the roots of Scutellaria baicalensis Georgi against hydrogen peroxide-induced oxidative stress in HS-SY5Y cells. Pharmacol Res. 43:173-178.
Gao D., Sakurai K., Chen J., Ogiso T., 1995. Protection by baicalein against ascorbic acid-induced lipid peroxidation of rat liver microsomes. Res Commun Mol Pathol Pharmacol. 90:103-114.
Geller SA., 2000. Hepatitis B and hepatitis C. Clin Liver Dis 6 : 317-334.
Guo Q., Zhao L., You Q., Yang Y., Gu H., Song G., Lu N., Xin J., 2007. Anti-hepatitis B virus activity of wogonin in vitro and in vivo. Antiviral Res 74 : 16-24.
Habtemariam S., 1997. Flavonoids as inhibitors or enhancers of the cytotoxicity of tumor necrosis factor-alpha in L-929 tumor cells. J Nat Prod. 60:775-778.
Huang ST., Wang CY., Yang RC., Chu CJ., Wu HT., Pang JH., 2009. Wogonin, an active compound in Scutellaria baicalensis, induces apoptosis and reduces telomerase activity in the HL-60 leukemia cells. Phytomedicine.
Ishizaki T., Sasaki F., Ameshima S., Shiozaki K., Takahashi H., Abe Y., Ito S., Kuriyama M., Nakai T., Kitagawa M., 1996. Pneumonitis during interferon and/or herbal drug therapy in patients with chronic active hepatitis. J Eur Resp 9 : 2691-2696.
Isis M, van Loon, N.D., 1997. The golden root: Clinical applications of Scutellaria baicalensis georig flavonoids as modulators of the inflammatory response. Alt Med Rev 2 : 472-480.
Jammeh S., Tavner F., Waston R., Thomas HC., Karayiannis P., 2008. Effect of basal core promoter and pre-core mutations on hepatitis B virus replication. J Gen Virol 89 : 901-909.
Jules L. Dienstag, M.G., 2009. Hepatitis B virus infection. N Engl J Med 359 : 1486-1500.
Lai CL., Ching CK., Tung AKM., Li E., Y., Young J., Hill A., Wong BCY., Dent J., Wu PC., 1997. Lamivudine is effective in suppressing hepatitis B virus DNA in Chinese hepatitis B surface antigen carriers: a placebo-controlled trial. Hepatology 25 : 241-244.
Liu IX., Durham DG., Richards RM.,, 2000. Baicalin synergy with beta-lactam antibiotics against methicillin-resistant Staphylococcus aureus and other beta-lactam-resistant strains of S. aureus. J Pharm Pharmacol 52 : 361-366.
Li BQ., Fu T., Dongyan Y., Mikovits JA., Ruscetti FW., Wang JM., 2000. Flavonoid baicalin inhibits HIV-1 infection at the level of viral entry. Biochem Biophys Res Commun 276 : 534-538.
Li BQ., Fu T., Gong WH., Dunlop N., Kung H., Yan Y., Kang J., Wang JM., 2000. The flavonoid baicalin exhibits anti-inflammatory activity by binding to chemokines. Immunopharmacology. 49:295-306
Liu JJ., Huang TS., Cheng WF., Lu FJ., 2003. Baicalein and baicalin are potent inhibitors of angiogenesis: Inhibition of endothelial cell proliferation, migration and differentiation. Int J Cancer. 106:559-565.
Li Z., Li LJ., Sun Y., Li J., 2007. Identification of natural compounds with anti-hepatitis B virus activity from Rheum palmatum L. ethanol extract. Chemotherapy 53 : 320-326.
Moolla N., Kew M., Arbuthnot P., 2002. Regulatory elements of hepatitis B virus transcription. J Viral Hepat 9 : 323-331.
Nassal M., Schaller H., 1996. Hepatitis B virus replication--an update. J Viral Hepatitis 3 : 217-226.
Oka H., Yamamoto S., Kuroki T., Harihara S., Marumo T., Kim SR., Monna T., Kobayashi K., Tango T., 1995. Prospective study of chemoprevention of hepatocellular carcinoma with Sho-saiko-to (TJ-9). Cancer. 76:743-749.
Okita K., Li Q., Murakamio T., Takahashi M., 1993. Anti-growth effects with components of Sho-saiko-to (TJ-9) on cultured human hepatoma cells. Eur J Cancer Prev. 2:169-175.
Pollack JR, Ganem D., 1994. Site-specific RNA binding by a hepatitis B virus reverse transcriptase initiates two distinct reactions: RNA packaging and DNA synthesis. J Virol 68 : 5579-5587.
Seeger C., Mason WS., 2000. Hepatitis B virus biology. Microbiol Mol Biol Rev 64 : 51-68.
Tan A., Yeh SH., Liu CJ., Cheung C and Chen PJ., 2008. Viral hepatocarcinogenesis : from infection to cancer. Liver Int 28 : 175-188.
Tang H., McLachian A., 2001. Transcriptional regulation of hepatitis B virus by nuclear hormone receptors is a critical determinant of viral tropism. Proc Natl Acad Sci USA 98 : 1841-1846.
Wang HK., Xia Y., Yang ZY., Natschke SL., Lee KH., 1998. Recent advances in the discovery and development of flavonoids and their analogues as antitumor and anti-HIV agents. Adv Exp Med Biol 439 : 191-225.
Wu JA., Attles AS., Zhang L., Yuan CS., 2001. Anti-HIV activity of medicinal herbs: usage and potential development. Am J Chin Med 29 : 69-81.
Yuh CH., Chang YL., Ting LP., 1992. Transcriptional regulation of precore and pregenomic RNAs of hepatitis B virus. J Virol 66 : 4073-4084.
Yuh CH., Ting LP., 1990. The genome of hepatitis B virus contains a second enhancer: cooperation of two elements within this enhancer is required for its function. J Virol 64 : 4281-4287.
Zhang DY., Wu J., Ye F., Xue L., Jiang S., Yi J., Zhang W., Wei H., Sung M., Wang W., Li X., 2003. Inhibition of cancer cell proliferation and prostaglandin E2 synthesis by Scutellaria baicalensis. Cancer Res. 63:4037-4043.
Zhang HW., Yang Y., Zhang K., Qiang L., Yang L., Yang L., Hu Y., Wang XT., You QD., Guo QL., 2008. Wogonin induced differentiation and G1 phase arrest of human U-937 leukemia cells via PKCdelta phosphorylation. Eur J Pharmacol. 591:7-12.
Zhou Z., Zang Y., Ding XR., Chen SH., Yang J., Wang XJ., Jia GJ., Chen HS., Bo XC., Wang SQ., 2007. Protocatechuic aldehyde inhibits hepatitis B virus replication both in vitro and in vivo. Antiviral Res 74 : 59-64.
Zoulim F., Seeger C., 1994. Reverse transcription in hepatitis B viruses is primed by a tyrosine residue of the polymerase. J Virol 68 : 6-13.
Zuckerman AJ., 1999. More than third of world’s population has been infected with hepatitis B virus. BMJ 318 : 1213.
QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top