大葉桃花心木萃取物抗C型肝炎病毒活性篩選

利用C型肝炎病毒複製子之篩藥系統，從一系列的大葉桃花心木（Swietenia macrophylla King）萃取物中篩選出有效抑制C型肝炎病毒的活性層。最後找到一個純化合物，此純化合物屬於lignan家族將之命名為5-HCL-C並發現此化合物具有抑制C型肝炎病毒複製的活性。EC50及CC50分別是11和27μM，其SI值（selective index value）為2.45。在感染系統裡5-HCL-C也具有抑制C型肝炎病毒複製的效果。另一個steroid家族的化合物命名為SMS-7，此化合物具有抑制C型肝炎病毒複製的活性，EC50是29.6μM而CC50是82.6μM；其SI值（selective index value）為2.78。除此之外嘗試將5-HCL-C結合使用IFN-α，NM107或VX-950皆有觀察到在抑制C型肝炎病毒複製方面有加成效果。此外我們發現5-HCL-C皆可有抑制RdRp，protrase和IRES活性的產生但卻沒有專一性的結果。此外很多文獻指出植物的初萃物或是所分離萃取得到的化合物具有抗發炎的活性。而轉錄因子－NF-κB，nuclear factor kappa B，在發炎反應中扮演重要的角色。因此，測得在經由處理5-HCL-C的條件下C型肝炎病毒RNA層面的NF-κB表現量並發現在C型肝炎病毒複製子系統和轉染的系統裡皆可觀察到NF-κB的表現量有減少的現象。Cox-2，cyclooxygenase-2，這個蛋白質會受到NF-κB的下游調控。在轉染系統裡也可測得cox-2的活性表現並發現在處理5-HCL-C的條件下cox-2的活性表現並沒有明顯的受到影響。因此推測5-HCL-C 之所以具有抑制C型肝炎病毒活性的原因可能在調控NF-κB的活性但並不是經由調控發炎反應的路徑。最後總結出從大葉桃花心木萃取出的5-HCL-C化合物可能可以進一步利用化學合成方法合成出其衍生物來發展出有效治療抑制C型肝炎病毒感染的藥劑。

關鍵字

C型肝炎病毒；大葉桃花心木；木脂素類化合物； NF-kB訊號傳導途徑

並列摘要

Based on HCV replicon screening system, we screened a series of crude extracts of Swietenia macrophylla King and found a pure compound which belonging to lignan family, termed 5-HCL-C, that could exhibit the inhibitory effect on HCV replication. The 50% effective and cytotoxity concentration (EC50 and CC50) were 11 and 27 μM, respectively, and the SI value (selective index, CC50 /EC50) was 2.45. And on HCV infectious system, 5-HCL-C treatment also showed anti-HCV activity in a dose-dependent manner. The other compound which belonging to steroid family and named SMS-7, showed a 50% effective concentration (EC50) was 29.6μM on HCV replication. And the 50% cytotoxity concentration (CC50) was 82.6 μM. The SI value (selective index, CC50 /EC50) was 2.78. In addition, 5-HCL-C treatment was double combination with IFN-α, NM107 or VX-950 indicated the additive effects on anti-HCV replication. Moreover, 5-HCL-C could weak inhibit the activity of RNA dependent RNA polymerase (RdRp), protease and internal ribosome entry site (IRES) but did not the target on anti-HCV replication. Furthermore, many reports had been indicated that the crude extracts or pure compounds of plants showed the anti-inflammatory activity. And the transcription factor－NF-κB，nuclear factor kappa B，plays an important role in the inflammatory pathway. Besides, we detected the expression of NF-κB on HCV RNA level showed 5-HCL-C treatment could inhibited the expression of NF-κB. Therefore, we found that the expression of NF-κB both decreased on HCV replicon system and transfection system. The expression of cox-2, cyclooxygenase-2, would affect by NF-κB down-regulation. Base on transfection system, we also found the activity of cox-2 did not affect by 5-HCL-C treatment. A result indicated that 5-HCL-C inhibited HCV replication via regulating the activity of NF-κB but not through inflammatory pathway. We concluded that pure compound of Swietenia macrophylla King could potentially be developed the derivatives of 5-HCL-C by chemical synthesis as a treatment for HCV infection.

並列關鍵字

HCV ； Swietenia macrophylla King ； lignan family ； NF-kB signal pathway

參考文獻

中藥化學/吳立軍主編台北市：科技圖館，2006

Google Scholar

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