Anti-hepatitis C virus activity of crude extract and fractions of Entada africana in genotype 1b replicon systems

TY - JOUR

T1 - Anti-hepatitis C virus activity of crude extract and fractions of Entada africana in genotype 1b replicon systems

AU - Galani Tietcheu, Borris Rosnay

AU - Sass, Gabriele

AU - Njayou, Nico Frederic

AU - Mkounga, Pierre

AU - Tiegs, Gisa

AU - Moundipa, Paul Fewou

PY - 2014/1/1

Y1 - 2014/1/1

N2 - 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.

AB - 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.

KW - 2',5'-Oligoadenylate Synthetase

KW - Cell Line, Tumor

KW - Cell Survival

KW - Depression, Chemical

KW - Dose-Response Relationship, Drug

KW - Fabaceae

KW - Genotype

KW - Heme Oxygenase-1

KW - Hepacivirus

KW - Hepatocytes

KW - Humans

KW - Plant Extracts

KW - Replicon

KW - Virus Replication

U2 - 10.1142/S0192415X14500542

DO - 10.1142/S0192415X14500542

M3 - SCORING: Journal article

C2 - 25004879

VL - 42

SP - 853

EP - 868

JO - AM J CHINESE MED

JF - AM J CHINESE MED

SN - 0192-415X

IS - 4

ER -