title: Anti-hepatitis C virus activity of 3-hydroxy caruilignan C from Swietenia macrophylla stems.
abstract: Chronic hepatitis C virus (HCV) infection ultimately leads to chronic hepatitis, hepatic cirrhosis and hepatocellular carcinoma (HCC). As the standard treatment is not completely efficacious, a safer and more effective agent against HCV infection needs to be developed. In this report, we demonstrated that 3-hydroxy caruilignan C (3-HCL-C) isolated from Swietenia macrophylla stems exhibited high anti-HCV activity at both protein and RNA levels at nontoxic concentrations, with an EC(50) value of 10.5 ± 1.2 μm. Combinations of 3-HCL-C and interferon-α (IFN-α), an HCV NS5B polymerase inhibitor (2'-C-methylcytidine; NM-107) or an HCV NS3/4A protease inhibitor (Telaprevir; VX-950) increased the suppression of HCV RNA replication. The results suggested that 3-HCL-C may be a potential anti-viral agent. We then demonstrated that 3-HCL-C interfered with HCV replication by inducing IFN-stimulated response element transcription and IFN-dependent anti-viral gene expression.
authors.affiliation: Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Taichung, Taiwan.
authors.forename: S-F
authors.initials: SF
authors.lastname: Wu
authors.forename: C-K
authors.initials: CK
authors.lastname: Lin
authors.forename: Y-S
authors.initials: YS
authors.lastname: Chuang
authors.forename: F-R
authors.initials: FR
authors.lastname: Chang
authors.forename: C-K
authors.initials: CK
authors.lastname: Tseng
authors.forename: Y-C
authors.initials: YC
authors.lastname: Wu
authors.forename: J-C
authors.initials: JC
authors.lastname: Lee
mesh_terms: D000998:Antiviral Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D016174:Hepacivirus / Q000187:drug effects*; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology; D017705:Lignans / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D029582:Meliaceae / Q000737:chemistry*; D008826:Microbial Sensitivity Tests; D009842:Oligopeptides / Q000494:pharmacology; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D018547:Plant Stems / Q000737:chemistry; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D017705:Lignans; D009842:Oligopeptides; D010936:Plant Extracts; C486464:telaprevir