Anti-hepatitis C virus activity of Acacia confusa extract via suppressing cyclooxygenase-2
Anti-hepatitis C virus activity of Acacia confusa extract via suppressing cyclooxygenase-2
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DOI：
10.1016/j.antiviral.2010.11.003
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发表时间：
2011-01-01
影响因子：
7.6
通讯作者：
Wu, Yang-Chang
中科院分区：
文献类型：
--
作者：
Lee, Jin-Ching;Chen, Wei-Chun;Wu, Yang-Chang
慢性丙型肝炎病毒(HCV)感染仍然是全世界慢性肝炎、肝硬变和肝细胞癌(HCC)发病率和死亡率的重要原因。寻找更有效、更安全的药物对提高丙型肝炎病毒携带者的临床治疗水平具有重要意义。本文报道了从相思植物中提取的正丁醇-甲醇提取物ACSB-M4在丙型肝炎病毒复制子检测系统中对丙型肝炎病毒RNA复制的抑制作用，其EC50值和CC50/EC50选择指数(SI)分别为5+/-0.3微克/毫升和>；100。此外，经多元线性Logistic模型和同源图谱分析，ACSB-M4与干扰素-α、丙型肝炎病毒蛋白水解酶抑制剂(telaprevir；VX-950)和聚合酶抑制剂(2‘-C-甲基胞苷；NM-107)具有协同抗病毒作用。通过在ACSB-M4处理的丙型肝炎病毒复制子细胞中过表达COX-2蛋白的互补方法，在分子水平上评价其抗病毒作用。ACSB-M4可显著抑制丙型肝炎病毒复制子细胞COX-2的表达。当ACSB-M4与COX-2同时加入时，病毒复制逐渐恢复，提示ACSB-M4的抗丙型肝炎病毒活性与COX-2的下调有关，而COX-2的下调与核因子-kappaB(NF-kappaB)的激活抑制有关。ACSB-M4可作为一种潜在的保护剂用于慢性丙型肝炎患者的治疗。皇冠版权所有(C)2010年，爱思唯尔BM出版。版权所有。
Chronic hepatitis C virus (HCV) infection continues to be an important cause of morbidity and mortality by chronic hepatitis, cirrhosis and hepatocellular carcinoma (HCC) throughout the world. It is of tremendous importance to discover more effective and safer agents to improve the clinical treatment on HCV carriers. Here we report that the n-butanol-methanol extract obtained from Acacia confusa plant, referred as ACSB-M4, exhibited the inhibition of HCV RNA replication in the HCV replicon assay system, with an EC50 value and CC50/EC50 selective index (SI) of 5 +/- 0.3 mu g/ml and >100, respectively. Besides, ACSB-M4 showed antiviral synergy in combination with IFN-alpha and as HCV protease inhibitor (Telaprevir; VX-950) and polymerase inhibitor (2'-C-methylcytidine; NM-107) by a multiple linear logistic model and isobologram analysis. A complementary approach involving the overexpression of COX-2 protein in ACSB-M4-treated HCV replicon cells was used to evaluate the antiviral action at the molecular level. ACSB-M4 significantly suppressed COX-2 expression in HCV replicon cells. Viral replication was gradually restored if COX-2 was added simultaneously with ACSB-M4, suggesting that the anti-HCV activity of ACSB-M4 was associated with down-regulation of COX-2, which was correlated with the suppression of nuclear factor-kappaB (NF-kappa B) activation. ACSB-M4 may serve as a potential protective agent for use in the management of patients with chronic HCV infection. Crown Copyright (C) 2010 Published by Elsevier BM. All rights reserved.