碩士 / 高雄醫學大學 / 生物科技學系碩士班 / 100 / Hepatitis C virus (HCV) is one of the most important human pathogens due to frequently lead to chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma (HCC). Current IFN-based therapies are ineffective in many patients infected by HCV, and they are plagued with adverse effects, underscoring the need for new therapeutic strategies. Here we reported that the aqueous extract obtained from Gracilaria tenuistipitata, referred as AEGT, exhibited the inhibition of HCV RNA replication in the HCV replicon system and infectious system, with an EC50 value of 302 and 296 μg/ml, respectively. Besides, the anti-HCV effect can be synergistic when AEGT was combined with IFN-α by a multiple linear logistic model and isobologram analysis. Activation of cyclooxygenase-2 (COX-2) has been implicated in the HCV-associated hepatocellular carcinoma. In our studies, we demonstrated that AEGT significantly inhibited COX-2 expression in HCV replicon cells. In cotrast, the recovery effect of HCV replication was observed in AEGT-treated replicon cells with increased COX-2 protein expression, suggesting that the anti-HCV activity of AEGT was associated with down-regulation of COX-2 gene expression, which was mediated by the suppression of nuclear factor-kappaB (NF-κB) activation. Finally, we also found that AEGT inhibits NS5A-induced and LPS-induced pro-inflammatory mediators including TNF-α, IL-1β, IL-6, iNOS and COX-2 in Huh7 cells and RAW264.7 cells, respectively. These findings provide the possibility that AEGT could be an excellent adjuvant or drug in the treatment of inflammation and chronic HCV infection.
| Identifer | oai:union.ndltd.org:TW/100KMC05111001 |
| Date | January 2011 |
| Creators | Kuan-Jen Chen, 陳冠任 |
| Contributors | Jin-Ching Lee, 李景欽 |
| Source Sets | National Digital Library of Theses and Dissertations in Taiwan |
| Language | zh-TW |
| Detected Language | English |
| Type | 學位論文 ; thesis |
| Format | 86 |
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