Abstract
Hepatitis C virus (HCV) is an important human pathogen leading to hepatocellular carcinoma. Using an in vitro cell-based HCV replicon and JFH-1 infection system, we demonstrated that an aqueous extract of the seaweed Gracilaria tenuistipitata (AEGT) concentration-dependently inhibited HCV replication at nontoxic concentrations. AEGT synergistically enhanced interferon-α (IFN-α) anti-HCV activity in a combination treatment. We found that AEGT also significantly suppressed virus-induced cyclooxygenase-2 (COX-2) expression at promoter transactivation and protein levels. Notably, addition of exogenous COX-2 expression in AEGT-treated HCV replicon cells gradually abolished AEGT anti-HCV activity, suggesting that COX-2 down-regulation was responsible for AEGT antiviral effects. Furthermore, we highlighted the inhibitory effect of AEGT in HCV-induced pro-inflammatory gene expression such as the expression of tumour necrosis factor-α, interleukin-1β, inducible nitrite oxide synthase and COX-2 in a concentration-dependent manner to evaluate the potential therapeutic supplement in the management of patients with chronic HCV infections.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antiviral Agents / pharmacology
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Antiviral Agents / therapeutic use
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Cell Line, Tumor
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Cyclooxygenase 2 / genetics
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Cyclooxygenase 2 / metabolism*
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Down-Regulation / drug effects*
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Drug Synergism
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Gracilaria / chemistry*
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Hepacivirus / drug effects*
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Hepacivirus / metabolism
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Hepacivirus / physiology
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Humans
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Inflammation / drug therapy
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Inflammation / genetics
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Inflammation / metabolism
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Inflammation / virology
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Interferon-alpha / pharmacology
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Interleukin-1beta / genetics
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NF-kappa B / metabolism
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Nitric Oxide Synthase Type II / genetics
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Plant Extracts / pharmacology*
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Plant Extracts / therapeutic use
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Plants, Edible / chemistry
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RNA, Viral / biosynthesis
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Tumor Necrosis Factor-alpha / genetics
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Viral Nonstructural Proteins / biosynthesis
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Viral Nonstructural Proteins / metabolism
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Viral Proteins / biosynthesis
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Virus Replication / drug effects*
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Water / chemistry*
Substances
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Antiviral Agents
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Interferon-alpha
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Interleukin-1beta
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NF-kappa B
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Plant Extracts
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RNA, Viral
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Tumor Necrosis Factor-alpha
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Viral Nonstructural Proteins
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Viral Proteins
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Water
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Nitric Oxide Synthase Type II
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Cyclooxygenase 2
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NS-5 protein, hepatitis C virus