English  |  正體中文  |  简体中文  |  Items with full text/Total items : 17918/22935 (78%)
Visitors : 6796463      Online Users : 177
RC Version 7.0 © Powered By DSPACE, MIT. Enhanced by NTU Library IR team.
Scope Tips:
  • please add "double quotation mark" for query phrases to get precise results
  • please goto advance search for comprehansive author search
  • Adv. Search
    HomeLoginUploadHelpAboutAdminister Goto mobile version
    Please use this identifier to cite or link to this item: https://ir.csmu.edu.tw:8080/ir/handle/310902500/1024


    Title: I:原兒茶酸對於lipopolysaccharide誘發鼠肝毒性之抑制作用II:Esculetin抑制癌細胞生長之作用及影響細胞週期之分子機制探討
    I:Inhibitory effects of lipopolysaccharide-induced rat liver toxicity of protocatechuic acid.II:Effects of inhibitting cancer cell growth and molecular mechanism of affecting cell cycle on esculetin.
    Authors: 謝育津
    Yu-Jin Hsieh
    Contributors: 中山醫學院:生物化學研究所;曾翠華
    Keywords: 原兒茶酸
    protocatechuic acid
    Date: 1998
    Issue Date: 2010-04-01T06:48:21Z (UTC)
    Abstract: Part I
    原兒茶酸(protocatechuic acid:PCA)廣佈於蔬菜、水果、花和胡桃中,乃一結構簡單的多酚類化合物。過去本研究室從中國傳統藥物亦是台灣普受歡迎的洛神花茶中分離出此化合物,並分析其具有抗氧化及抗癌化之生物活性。由實驗中發現腹腔注射5mg/kg的LPS 6小時後,可誘發血清肝功能指標AST、ALT生化值的升高,肝組織GSH的減少,NO的大量生成,iNOS活性及蛋白表現量的增加,轉錄因子NFκB的活化及肝組織之病變,然對膜的脂質過氧化物MDA及抗氧化酵素catalase、GSH peroxidase則無意義之影響。而預先口服5天高劑量(75mg/kg)的原兒茶酸則能有效抑制LPS所誘發的肝毒性。
    PART II
    Eesculetin( 6,7-dihydroxycoumarin)是香豆精的衍生物之一,常見於藥用植物如菊科的茵陳蒿、芸香科的橙柚、玄參科的毛地黃、大戢科的續隨、茄科的顛茄、蔓陀羅等,為一種多酚類化合物。過去本研究在抗氧化天然物開發中發現其具有不錯的抗氧化和抗發炎之作用,而近年來有文獻報告香豆精衍生物(如:1,2-benzopyrone、7-hy-droxycoumarin)對人類惡性細胞株皆具有抑制生長的作用,然分子之作用機制仍不甚清楚。
    近年來有許多研究指出一些抗癌藥物可藉由引起癌細胞的程序式死亡或改變癌細胞的生長週期,來達到抑制癌細胞的增生與惡化。至目前為止,對於程序式死亡的機制雖然仍不甚清楚,但一般認為細胞在接收到死亡訊息後,可能藉由改變內在target(如粒腺體)的正常功能,進而活化一些酵素(如:CPP32、PARP-γ),導致細胞死亡。此外,調節細胞週期進行的蛋白cyclin、cyclin-dependent kinase及cyclin-dependent kinase inhibitor 與腫瘤形成有極密切的關係。在本實驗中,觀察到esculetin可以抑制人類血癌細胞株(HL-60)及肝癌細胞株(HepG2、H3B)的生長;由流速細胞儀測定顯示esculetin可使HL-60及H3B細胞週期停滯在G1 phase和HepG2細胞週期停滯在S phase,而且發現以esculetin出處理24小時,可誘發HL-60 apoptosis, 但H3B、HepG2則無。另由西方點墨法發現esculetin誘發HL-60 apoptosis是透過cytochrome c釋出活化CPP32,促使PARP-γ裂解;亦觀察到esculetin導致HL-60細胞G1 phase停滯主要和cyclin D及Cdk-4有關,而H3B細胞則和cyclin E有關。此外也發現esculetin處理H3B細胞,p38MAPK的磷酸化會增加,但對phospho-MAPK則無意義之影響。
    Part I
    A simple phenolic compound,protocatechuic acid,is ubiquitous in edible vegetables、fruits and nuts. In our previous study, protocatechuic acid(PCA) possessing antioxidant property and anticarcinogenic potentials was isolated from Chinese traditional herbs and beverage materail in local region(Taiwan). In this experiment,we found that lipopolysaccharide (5mg/kgLPS i.p. for 6 hrs) significantly increased the serum hepatic enzyme markers(AST and ALT)、serum total nitrite and iNOS activity in rats. In addition, LPS significantly decreased GSH, activated iNOS and NFκB of liver and inhanced liver lesion including liver cell congestion、necrosis and cellular infiltration of inflammatory leukocyte. However, the group of pretreatment 75mg/kg protocatechuic acid for five days effectively inhibit LPS-induced hepatotoxicity. So, we concluded that PCA may play a role in endotoxin-induced liver damage.
    PART II
    Esculetin, a phenolic compound, is a coumarin derivative containing in many plants such as Atemisiae capillaris Flos (Com-positae), leaves of Citrus limonia(Rutaceae), Digitalis pur-purea L. (Scrophulariaceae), Euphorbia lathyris L. (Eupho-biaceae), Atropa belladonna(Solanaceae), Datura stramonium L. (Solanceae) Hyoscyamus niger L.(Solanceae). Previously, we found that esculetin exhibited antioxidant and anti-inflammatory bioactivities. It is reported that coumarin derivatives can inhibit the proliferation of human malignant cell lines. However, the molecular mechanism of anti-proliferation of these compound are remain to be defined.
    To date, the mechanism about apoptosis(programmed cell death) was unclear. It is supposed generally that a promising chemotherapeutic agent will have to promote the cell entering to go these two pathway.The exploration of intrinsic and extrinsic modulation of chemotherapeutic agents may prove the efficency of anticancer treatment. Recently, some studys suggest that anticancer drugs may induce cancer cell apoptosis or change cell cycle to prevent the cancer cell prolifaration. In this present, the ability of esculetin to inhibit cell growth.The flow cytometry analysis shows the esculetin can arrest at G1 phase for HL-60 and H3B and can arrest S phase for HepG2. Also, we found HL-60 cell treatment with esculetin for 24 hours can significantly reduced the content of cyclin D and Cdk-4 and H3B cell treatment with esculetin can reduced the content of cyclin D and E、increase of p38MAPK phosphorylation. Finally, we observe the effect of esculetin to some apoptosis associated protein. Esculetin treatment of HL-60 cells can induce cytochrome c releasing from mitochondria and breakage of PARP-γ.
    URI: http://140.128.138.153:8080/handle/310902500/1024
    Appears in Collections:[生化微生物免疫研究所] 博碩士論文

    Files in This Item:

    There are no files associated with this item.



    SFX Query

    All items in CSMUIR are protected by copyright, with all rights reserved.


    DSpace Software Copyright © 2002-2004  MIT &  Hewlett-Packard  /   Enhanced by   NTU Library IR team Copyright ©   - Feedback