title: Aqueous extract of the edible Gracilaria tenuistipitata inhibits hepatitis C viral replication via cyclooxygenase-2 suppression and reduces virus-induced inflammation.
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.
authors.affiliation: Department of Biotechnology, College of Life Science, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Kuan-Jen
authors.initials: KJ
authors.lastname: Chen
authors.forename: Chin-Kai
authors.initials: CK
authors.lastname: Tseng
authors.forename: Fang-Rong
authors.initials: FR
authors.lastname: Chang
authors.forename: Jin-Iong
authors.initials: JI
authors.lastname: Yang
authors.forename: Chi-Chen
authors.initials: CC
authors.lastname: Yeh
authors.forename: Wei-Chun
authors.initials: WC
authors.lastname: Chen
authors.forename: Shou-Fang
authors.initials: SF
authors.lastname: Wu
authors.forename: Hsueh-Wei
authors.initials: HW
authors.lastname: Chang
authors.forename: Jin-Ching
authors.initials: JC
authors.lastname: Lee
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use; D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects*; D004357:Drug Synergism; D044724:Gracilaria / Q000737:chemistry*; D016174:Hepacivirus / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000821:virology; D016898:Interferon-alpha / Q000494:pharmacology; D053583:Interleukin-1beta / Q000235:genetics; D016328:NF-kappa B / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use; D010945:Plants, Edible / Q000737:chemistry; D012367:RNA, Viral / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D017361:Viral Nonstructural Proteins / Q000096:biosynthesis / Q000378:metabolism; D014764:Viral Proteins / Q000096:biosynthesis; D014779:Virus Replication / Q000187:drug effects*; D014867:Water / Q000737:chemistry*; D012324:RNA-Dependent RNA Polymerase
chemical_list: D000998:Antiviral Agents; D051546:Cyclooxygenase 2; D016898:Interferon-alpha; D053583:Interleukin-1beta; D016328:NF-kappa B; D052247:Nitric Oxide Synthase Type II; D010936:Plant Extracts; D012367:RNA, Viral; D014409:Tumor Necrosis Factor-alpha; D017361:Viral Nonstructural Proteins; D014764:Viral Proteins; D014867:Water; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase