title: Gallic acid decreases hepatitis C virus expression through its antioxidant capacity.
abstract: Gallic acid (GA) is a natural phenolic compound that possesses various biological effects, including antioxidant, anti-inflammatory, antibiotic, anticancer, antiviral and cardiovascular protection activities. In addition, numerous studies have reported that antioxidants possess antiviral activities. Hepatitis C virus (HCV) is one of the most important causes of chronic liver diseases worldwide, but until recently, only a small number of antiviral agents had been developed against HCV. Therefore, the present study investigated whether GA exhibits an anti-HCV activity. The effects of GA on HCV expression were examined using a subgenomic HCV replicon cell culture system that expressed HCV nonstructural proteins (NSs). In addition, GA cytotoxicity was evaluated at concentrations between 100-600 mg/ml using an MTT assay. Huh-7 replicon cells were incubated with 300 mg/ml GA for different times, and the HCV-RNA and protein levels were measured by reverse transcription-quantitative polymerase chain reaction and western blot analysis, respectively. Pyrrolidine dithiocarbamate (PDTC) was used as an antioxidant control and reactive oxygen species (ROS) production was measured during the exposure. The results indicated that GA did not produce a statistically significant cytotoxicity in parental and HCV replicon cells. Furthermore, GA downregulated the expression levels of NS5A-HCV protein (~55%) and HCV-RNA (~50%) in a time-dependent manner compared with the levels in untreated cells. Notably, GA treatment decreased ROS production at the early time points of exposure in cells expressing HCV proteins. Similar results were obtained upon PDTC exposure. These findings suggest that the antioxidant capacity of GA may be involved in the downregulation of HCV replication in hepatoma cells.
authors.affiliation: Food Research Department, School of Chemical Sciences, Autonomous University of Coahuila, Saltillo Unit, Saltillo, Coahuila 25260, México; Department of Biochemistry and Molecular Medicine, School of Medicine, Autonomous University of Nuevo Leon, Monterrey, Nuevo Leon 66450, México.
authors.forename: Mayela
authors.initials: M
authors.lastname: Govea-Salas
authors.affiliation: Department of Biochemistry and Molecular Medicine, School of Medicine, Autonomous University of Nuevo Leon, Monterrey, Nuevo Leon 66450, México.
authors.forename: Ana Maria
authors.initials: AM
authors.lastname: Rivas-Estilla
authors.affiliation: Food Research Department, School of Chemical Sciences, Autonomous University of Coahuila, Saltillo Unit, Saltillo, Coahuila 25260, México.
authors.forename: Raul
authors.initials: R
authors.lastname: Rodríguez-Herrera
authors.affiliation: Department of Biochemistry and Molecular Medicine, School of Medicine, Autonomous University of Nuevo Leon, Monterrey, Nuevo Leon 66450, México.
authors.forename: Sonia A
authors.initials: SA
authors.lastname: Lozano-Sepúlveda
authors.affiliation: Food Research Department, School of Chemical Sciences, Autonomous University of Coahuila, Saltillo Unit, Saltillo, Coahuila 25260, México.
authors.forename: Cristobal N
authors.initials: CN
authors.lastname: Aguilar-Gonzalez
authors.affiliation: Food Research Department, School of Chemical Sciences, Autonomous University of Coahuila, Saltillo Unit, Saltillo, Coahuila 25260, México.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Zugasti-Cruz
authors.affiliation: Department of Biochemistry and Molecular Medicine, School of Medicine, Autonomous University of Nuevo Leon, Monterrey, Nuevo Leon 66450, México.
authors.forename: Tanya B
authors.initials: TB
authors.lastname: Salas-Villalobos
authors.affiliation: Food Research Department, School of Chemical Sciences, Autonomous University of Coahuila, Saltillo Unit, Saltillo, Coahuila 25260, México; Clinical Laboratory Department, General Hospital Zone No. 2, Mexican Social Security Institute, Saltillo, Coahuila 25017, México.
authors.forename: Jesus Antonio
authors.initials: JA
authors.lastname: Morlett-Chávez
keywords: antioxidants; gallic acid; hepatitis C virus; oxidative stress