Chen Wei-Chun, Tseng Chin-Kai, Chen Bing-Hung, Lin Chun-Kuang, Lee Jin-Ching
Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University Kaohsiung, Taiwan.
Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung UniversityTainan, Taiwan; Center of Infectious Disease and Signaling Research, College of Medicine, National Cheng Kung UniversityTainan, Taiwan.
Front Pharmacol. 2016 Dec 21;7:490. doi: 10.3389/fphar.2016.00490. eCollection 2016.
Hepatitis C virus (HCV) infection is a causative factor leading to hepatocellular carcinoma due to chronic inflammation and cirrhosis. The aim of the study was first to explore the effects of grape seed extract (GSE) in HCV replication, and then to study mechanisms. The results indicated that a GSE treatment showed significant anti-HCV activity and suppressed HCV-elevated cyclooxygenase-2 (COX-2) expression. In contrast, exogenous COX-2 expression gradually attenuated antiviral effects of GSE, suggesting that GSE inhibited HCV replication by suppressing an aberrant COX-2 expression caused by HCV, which was correlated with the inactivation of IKK-regulated NF-κB and MAPK/ERK/JNK signaling pathways. In addition, GSE also attenuated HCV-induced inflammatory cytokine gene expression. Notably, a combined administration of GSE with interferon or other FDA-approved antiviral drugs revealed a synergistic anti-HCV effect. Collectively, these findings demonstrate the possibility of developing GSE as a dietary supplement to treat patients with a chronic HCV infection.
丙型肝炎病毒(HCV)感染是由于慢性炎症和肝硬化导致肝细胞癌的一个致病因素。该研究的目的首先是探究葡萄籽提取物(GSE)对HCV复制的影响,然后研究其作用机制。结果表明,GSE处理显示出显著的抗HCV活性,并抑制了HCV诱导的环氧化酶-2(COX-2)表达。相反,外源性COX-2表达逐渐减弱了GSE的抗病毒作用,这表明GSE通过抑制HCV引起的异常COX-2表达来抑制HCV复制,这与IKK调节的NF-κB和MAPK/ERK/JNK信号通路的失活相关。此外,GSE还减弱了HCV诱导的炎性细胞因子基因表达。值得注意的是,GSE与干扰素或其他美国食品药品监督管理局(FDA)批准的抗病毒药物联合给药显示出协同抗HCV作用。总体而言,这些发现证明了将GSE开发为治疗慢性HCV感染患者的膳食补充剂的可能性。