Grape Seed Extract Attenuates Hepatitis C Virus Replication and Virus-Induced Inflammation

Abstract

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.

May Polyphenols Have a Role Against Coronavirus Infection? An Overview of in vitro Evidence

“…Among these, grape pomace extract (GPE) has been reported as an excellent source of bioactive compounds, mainly polyphenols, including RSV, cathechins, and proanthocyanidins (31)(32)(33). Notably, evidence indicated the antiviral activity of GPE against various microorganisms, including human immunodeficiency virus type 1 (34), human enteric virus, human norovirus surrogates [feline calicivirus (FCV) F9 and murine norovirus (MNV-19)] (35), hepatitis A virus (36), and hepatitis C virus (HCV) (37). Different mechanisms of actions have been demonstrated, including downregulation of the HIV-1 entry co-receptor expression (for the activity against HIV) (34), suppression of virus replication via reduction of COX2 expression and regulation of NFκB and MAPK signaling pathways and reduction of virus-induced inflammation (for the anti-HCV activity) (37).…”

“…Notably, evidence indicated the antiviral activity of GPE against various microorganisms, including human immunodeficiency virus type 1 (34), human enteric virus, human norovirus surrogates [feline calicivirus (FCV) F9 and murine norovirus (MNV-19)] (35), hepatitis A virus (36), and hepatitis C virus (HCV) (37). Different mechanisms of actions have been demonstrated, including downregulation of the HIV-1 entry co-receptor expression (for the activity against HIV) (34), suppression of virus replication via reduction of COX2 expression and regulation of NFκB and MAPK signaling pathways and reduction of virus-induced inflammation (for the anti-HCV activity) (37). Interestingly, two in vitro studies investigated the effects of GPE against respiratory syncytial virus, using an airway epithelial A549 cell model (38,39).…”

An Evaluation of Traditional Persian Medicine for the Management of SARS-CoV-2

“…Grape seed extract has shown inhibitory effects on HCV replication via suppression of virus-induced cyclooxygenase (COX)-2 overexpression. It has also shown a synergistic effect by co-administration with conventional anti-HCV medicines including telaprevir, daclatasvir, sofosbuvir (Chen et al, 2016). Suppression of the MAPK/JNK pathway is also involved in the antiviral effect of grape seed extract against both HCV (Chen et al, 2016) and RSV (Lee et al, 2017).…”

“…It has also shown a synergistic effect by co-administration with conventional anti-HCV medicines including telaprevir, daclatasvir, sofosbuvir (Chen et al, 2016). Suppression of the MAPK/JNK pathway is also involved in the antiviral effect of grape seed extract against both HCV (Chen et al, 2016) and RSV (Lee et al, 2017). Moreover, the extract has prevented ILs, MAPK/JNK, and NF-kB pro-inflammatory cascades and regulated mucin production via reducing the expression of several mucin MUC genes in the airway epithelium.…”

Specific activation of pro-Infliximab enhances selectivity and safety of rheumatoid arthritis therapy

“…Human embryonic kidney cell line (HEK293) cells were transiently transfected with the luciferase reporter plasmid pNF-κB-Luc [45] (BD Biosciences Clontech, Palo Alto, CA, USA), internal control Renilla-Luc reporter plasmid, or positive control pFC-MEKK plasmid with TransIT-LT1 reagent (Mirus Bio, Madison, WI) for 6 h. After the transfection procedure, the medium was replaced with TNFα (20 ng/mL, Sigma-Aldrich) and incubated with Infliximab, pro-Infliximab, MMP-2/9 preincubated Infliximab, or MMP-2/9 preincubated pro-Infliximab for 1 h at 37 °C. After removing from the medium, the cells were cultured for 16 h at 37 °C, and cell extracts from each sample were measured using the dual-luciferase reporter assay system (Promega, Madison, WI, USA) according to the manufacturer’s protocol.…”