title: Anti-hepatitis C virus activity of crude extract and fractions of Entada africana in genotype 1b replicon systems.
abstract: Entada africana (Ea) is a medicinal plant from the family of Fabaceae, used in Western and Central Africa regions to treat liver diseases. Antiviral properties of this plant were reported against Hepatitis B virus, while effects against Hepatitis C virus (HCV) remained unknown. This study reports for the first time, the effects of Ea crude extract and fractions on HCV replication. Furthermore, the effect of one Ea fraction on the transcriptional expression of two interferon-stimulated genes (ISGs) was also investigated. A methylene chloride-methanol (MCM) stem bark crude extract and different MCM fractions (EaF0, EaF5, EaF10, EaF25, and EaF100) were prepared and tested on LucUbiNeo-ET and Huh 5.15 cells lines used as genotype 1b (GT1b) replicon systems. The cells were incubated with crude extract and fractions at various concentrations. Then, the antiviral activity was assessed by luciferase reporter assay and the cell viability by MTT assay. Gene expression was also analyzed using quantitative real time RT-PCR. Results showed that the Ea crude extract dose-dependently inhibited HCV replication after 24 and 72 h of incubation. The MCM fraction (EaF10) exhibited the strongest anti-HCV properties with an IC50 = 0.453 ± 0.00117 mg/ml and no reduction of cell viability at antiviral concentrations. This fraction also significantly induced the expression of heme oxygenase-1 (HO-1) (5.36-fold), and 2'-5' oligoadenylate synthetase-3 (OAS-3) by 4.46-fold after 6 h and 2.31-fold after 24 h at the mRNA levels. Taken altogether, these results suggest that Ea may contain ingredients that indirectly regulate HCV replication.
authors.affiliation: Laboratory of Pharmacology and Toxicology, University of Yaoundé I, Yaoundé, Cameroon , Department of Biological Sciences, Faculty of Science, University of Ngaoundéré, Ngaoundéré, Cameroon , Institute for Experimental Immunology and Hepatology, Center for Experimental Medicine, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Borris Rosnay
authors.initials: BR
authors.lastname: Galani Tietcheu
authors.forename: Gabriele
authors.initials: G
authors.lastname: Sass
authors.forename: Nico Frederic
authors.initials: NF
authors.lastname: Njayou
authors.forename: Pierre
authors.initials: P
authors.lastname: Mkounga
authors.forename: Gisa
authors.initials: G
authors.lastname: Tiegs
authors.forename: Paul Fewou
authors.initials: PF
authors.lastname: Moundipa
mesh_terms: D015088:2',5'-Oligoadenylate Synthetase / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D007887:Fabaceae; D005838:Genotype; D051547:Heme Oxygenase-1 / Q000378:metabolism; D016174:Hepacivirus / Q000235:genetics* / Q000502:physiology*; D022781:Hepatocytes / Q000821:virology*; D006801:Humans; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D012093:Replicon / Q000235:genetics*; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D010936:Plant Extracts; D051547:Heme Oxygenase-1; D015088:2',5'-Oligoadenylate Synthetase; C577439:OAS3 protein, human
keywords: 2′-5′Oligoadenylate Synthetase-3; Entada africana; Heme Oxygenase-1; Hepatitis C Virus