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

• Published in: PloS one Vol. 8; no. 2; p. e57704
• Main Authors: Chen, Kuan-Jen, Tseng, Chin-Kai, Chang, Fang-Rong, Yang, Jin-Iong, Yeh, Chi-Chen, Chen, Wei-Chun, Wu, Shou-Fang, Chang, Hsueh-Wei, Lee, Jin-Ching
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 28.02.2013; Public Library of Science (PLoS)
• Subjects: Algae; Amino acids; Antiviral Agents - pharmacology; Antiviral Agents - therapeutic use; Apoptosis; Biology; Biotechnology; Cancer; Cell Line, Tumor; Chemistry; Cyclooxygenase 2 - genetics; Cyclooxygenase 2 - metabolism; Cyclooxygenase-2; Cytomegalovirus; Down-Regulation - drug effects; Drug resistance; Drug Synergism; Gene expression; Gracilaria; Gracilaria - chemistry; Hepacivirus - drug effects; Hepacivirus - metabolism; Hepacivirus - physiology; Hepatitis; Hepatitis C; Hepatocellular carcinoma; Humans; Infections; Inflammation; Inflammation - drug therapy; Inflammation - genetics; Inflammation - metabolism; Inflammation - virology; Influenza; Interferon; Interferon-alpha - pharmacology; Interleukin-1beta - genetics; Interleukins; Kinases; Laboratories; Life sciences; Medicine; Natural products; NF-kappa B - metabolism; Nitric Oxide Synthase Type II - genetics; Pharmacy; Plant Extracts - pharmacology; Plant Extracts - therapeutic use; Plants, Edible - chemistry; Proteins; Replication; RNA, Viral - biosynthesis; Rodents; Studies; Transcription factors; Tumor necrosis factor; Tumor Necrosis Factor-alpha - genetics; Tumor necrosis factor-TNF; Tumors; Viral infections; Viral Nonstructural Proteins - biosynthesis; Viral Nonstructural Proteins - metabolism; Viral Proteins - biosynthesis; Virus Replication - drug effects; Viruses; Water - chemistry; West Nile virus; Taiwan
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0057704

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.