柴胡皂苷抑制C型肝炎病毒複製之能力探討

台灣地區約有百分之二至四的人口（約三十萬人）感染Ｃ型肝炎，長期的慢性感染可導致肝臟纖維化、肝硬化、甚至肝癌，因此有效的預防及治療C型肝炎病毒成為為國人健康把關的一大課題。目前臨床上合併長效型干擾素及雷巴威林之雞尾酒療法是目前治療慢性C型肝炎的標準療法，但由於其療效並非百分之百，加上副作用的影響甚大，因此中藥複方成為治療肝炎的另一途徑。小柴胡湯是常用於治療慢性肝炎的中藥方劑之一。它由七味中藥所組成，其中以柴胡為最重要的藥材（君藥）。柴胡的主要活性成分是柴胡皂苷（Saikosaponin, SS）。過去的研究發現Saikosaponin具有多項功能，在人體多項生理功能中均具有調節能力，包括免疫系統、細胞週期及細胞凋亡等等。最近的研究發現，在In vitro中柴胡皂苷可以抑制B型肝炎病毒（HBV）的複製，但對於C型肝炎病毒的影響則尚未見報導。因此本研究將利用一株Ava.5細胞株作為研究模式，它是包含C型肝炎病毒複製子（replicon）的肝癌細胞，利用它來探討Saikosaponin是否能夠直接抑制NS5A mRNA，或是影響HCV NS5A、NS3等蛋白的表現。另外也將利用Saikosaponin與干擾素併用於細胞株上，藉以探討Saikosaponin對於干擾素的抑制病毒能力是否有增強或減弱的作用。結果顯示，在Ava.5細胞株中，Saikosaponin可能無法直接抑制NS5A mRNA，以及影響HCV NS5A、NS3等蛋白表現的能力。另外，Saikosaponin合併Interferon-α2b處理細胞株，也無法加強Interferon- α2b其抗病毒的功效。

In Taiwan, hepatitis C virus (HCV) infection prevalence is estimated to be 2-4% in the general population. Chronic HCV infection could lead to liver fibrosis, cirrhosis and hepatocellular carcinoma. Therefore, the effective prevention and treatment for chronic HCV infection is an important healthcare problem. The current standard therapy for chronic HCV infection consists of a combination of pegylated IFN-α (pegIFN-α) and ribavirin. However, at most cases, such therapy couldn’t achieve a sustained viral clearance and often led to severe side effects. Thus, traditional Chinese medicine compound is another choice in treatment for chronic HCV infection. Sho-Saiko-To (Xiao-Chai-Hu -Tang) is one of formula in the traditional Chinese herbs and commonly used in treatment for chronic hepatitis. Saikosaponin is the main effective component of Bupleurum falcatum L., which is the most important herb in Sho-Saiko-To. Previous studies have shown that Saikosaponin has effects on various aspects, including immune system, cell cycle and cell apoptosis and so on. Recent researches show that Saikosaponin can suppress the duplication of hepatitis B virus (HBV) in vitro. But its influence on hepatitis C virus has not been reported. In this study, we used an Ava.5 cell line (derived from Huh 7 cell) which contains hepatitis C virus replicon to observe whether Saikosaponin has effects the expression of NS5A. Results showed that Saikosaponin was not able significantly reduce the level of NS5A RNA and the expression of NS5A and NS3 protein. Additionally, the combination of Saikosaponin and Interferon-α2b has no synergistic effects on the replication of HCV.