Aqueous extract of the edible Gracilaria tenuistipitata inhibits hepatitis C viral replication via cyclooxygenase-2 suppression and reduces virus-induced inflammation

PLoS One. 2013;8(2):e57704. doi: 10.1371/journal.pone.0057704. Epub 2013 Feb 28.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / pharmacology
  • Antiviral Agents / therapeutic use
  • Cell Line, Tumor
  • Cyclooxygenase 2 / genetics
  • Cyclooxygenase 2 / metabolism*
  • Down-Regulation / drug effects*
  • Drug Synergism
  • Gracilaria / chemistry*
  • Hepacivirus / drug effects*
  • Hepacivirus / metabolism
  • Hepacivirus / physiology
  • Humans
  • Inflammation / drug therapy
  • Inflammation / genetics
  • Inflammation / metabolism
  • Inflammation / virology
  • Interferon-alpha / pharmacology
  • Interleukin-1beta / genetics
  • NF-kappa B / metabolism
  • Nitric Oxide Synthase Type II / genetics
  • Plant Extracts / pharmacology*
  • Plant Extracts / therapeutic use
  • Plants, Edible / chemistry
  • RNA, Viral / biosynthesis
  • Tumor Necrosis Factor-alpha / genetics
  • Viral Nonstructural Proteins / biosynthesis
  • Viral Nonstructural Proteins / metabolism
  • Viral Proteins / biosynthesis
  • Virus Replication / drug effects*
  • Water / chemistry*

Substances

  • Antiviral Agents
  • Interferon-alpha
  • Interleukin-1beta
  • NF-kappa B
  • Plant Extracts
  • RNA, Viral
  • Tumor Necrosis Factor-alpha
  • Viral Nonstructural Proteins
  • Viral Proteins
  • Water
  • Nitric Oxide Synthase Type II
  • Cyclooxygenase 2
  • NS-5 protein, hepatitis C virus

Grants and funding

National Science Council of Taiwan (NSC 101-2311-B-037-002-MY3; NSC 101-2622-B-037-001-CC3) http://web1.nsc.gov.tw/, Kaohsiung Medical University Research Foundation, Taiwan (KMUER014) http://www2.kmu.edu.tw/index.phtml and Department of Health, Executive Yuan, Taiwan (DOH102-TD-C-111-002) http://www.doh.gov.tw/EN2006/index_EN.aspx. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.