2026-11-092026-11-09https://scholars.csmu.edu.tw/handle/123456789/38648Chronic liver damage induced by chemicals, such as toxicants, medicines and alcohol, is one of the major causes leading to liver cancer. Our previous study demonstrates that the extract of piper betel leaf (PBL) is able to prevent the liver cirrhosis induced by CCl4, and normalize the elevated serum AST and ALT levels. The mechanism for such action of PBL is via the activation of Ras, Raf and Erk pathway to inhibit TIMP2 and activate MMP2 that leads to the degradation of α -sma and, therefore, decreases the fibrosis of liver tissue. In this project, we intend to further evaluate the ability of PBL extract in treating liver diseases. First year: Aflatoxin and CCl4 will be used to induce damage in normal liver cells and in the liver of SD rats. The cells and animals will then be treated with PBL extract to observe whether the supplement is able to reverse the damage and regain cell and liver function. The mechanisms underline the action will be examined. Second year: The hepatic stellate Cells (HSC) will be isolated from normal and fibrotic liver tissues for primary culture to study whether PBL extract is able to repress the proliferation and activation of HSC and the mechanisms of the function. Third year: Surgical or chemical model will be used to generate liver cancer in SD rats that will then be provided with PBL extract to evaluate its therapeutic application and to analyze, also, the underlining mechanisms.慢性肝損傷一直是肝癌發生的主要原因之一。然而現在人的藥物酒 精濫用等不正常的生活作息，再加上肝臟是一個神經分部極少的臟 器，因此往往造成肝損傷的產生而不自知。由於我們先前實驗室的研 究中發現，荖葉的水萃取物能有效的預防四氯化碳所誘發的肝損傷， 並且在老鼠血液中的AST、ALT 能有顯著的下降，另一方面SOD、 CAT 的酵素活性皆有上升的現象。更進一步探討其影響的機制也發現 其主要是透過TIMP2 、Ras、Raf、Erk 訊息傳遞路徑使體內MMP2 蛋 白活化去降解α-sma 沉積造成肝臟纖維化的減少。因此在本計畫我們 擬定第一年在動物實驗以及細胞實驗方面，分別利用四氯化碳以及黃 麴毒素處理，再給予荖葉的水萃取物，看是否能有效回復正常肝功能 的現象；第二年再抽取老鼠肝臟星狀細胞的primary culture，更進一 步的分析是否能有效阻止其增生及活化的現象；第三年則以手術方式 造成肝癌的產生再給予荖葉的處理，是其是否具有治療性的影響，並 再更深一層面以細胞實驗進行探討其作用機轉為何。Project