Antiviral activities of Indonesian medicinal plants in the East Java region against hepatitis C virus

Tutik Sri Wahyuni,Evhy Apriani,Hak Hotta,Hiroyuki Fuchino,Achmad Fuad,Soetjipto Soetjipto,Ikuo Shoji,Aty Widyawaruyanti,Adita Ayu Permanasari,Nasronudin Nasronudin,Abdul Rahman,Myrna Adianti,Chie Aoki,Nobuo Kawahara,Maria Inge Lusida,Lydia Tumewu,Lin Deng

doi:10.1186/1743-422x-10-259

Abstract

BackgroundHepatitis C virus (HCV) is a major cause of liver disease and a potential cause of substantial morbidity and mortality worldwide. The overall prevalence of HCV infection is 2%, representing 120 million people worldwide. Current standard treatment using pegylated interferon and ribavirin is effective in only 50% of the patients infected with HCV genotype 1, and is associated with significant side effects. Therefore, it is still of importance to develop new drugs for treatment of HCV. Antiviral substances obtained from natural products, including medicinal plants, are potentially good targets to study. In this study, we evaluated Indonesian medicinal plants for their anti-HCV activities.MethodsEthanol extracts of 21 samples derived from 17 species of medicinal plants explored in the East Java region were tested. Anti-HCV activities were determined by a cell culture method using Huh7.5 cells and HCV strains of 9 different genotypes (1a to 7a, 1b and 2b).ResultsFour of the 21 samples tested showed antiviral activities against HCV: Toona sureni leaves (TSL) with 50% inhibitory concentrations (IC50) of 13.9 and 2.0 μg/ml against the HCV J6/JFH1-P47 and -P1 strains, respectively, Melicope latifolia leaves (MLL) with IC50 of 3.5 and 2.1 μg/ml, respectively, Melanolepis multiglandulosa stem (MMS) with IC50 of 17.1 and 6.2 μg/ml, respectively, and Ficus fistulosa leaves (FFL) with IC50 of 15.0 and 5.7 μg/ml, respectively. Time-of-addition experiments revealed that TSL and MLL inhibited both at the entry and post-entry steps while MMS and FFL principally at the entry step. TSL and MLL inhibited all of 11 HCV strains of all the genotypes tested to the same extent. On the other hand, FFL showed significantly weaker inhibitory activities against the HCV genotype 1a strain, and MMS against the HCV strains of genotypes 2b and 7a to a lesser extent, compared to the other HCV genotypes.ConclusionsEthanol extracts of TSL, MLL, MMS and FFL showed antiviral activities against all the HCV genotypes tested with the exception that some genotype(s) showed significant resistance to FFL and to MMS to a lesser extent. These plant extracts may be good candidates for the development of anti-HCV drugs.

Highlights

Hepatitis C virus (HCV) is a major cause of liver disease and a potential cause of substantial morbidity and mortality worldwide
Anti-HCV activities of ethanol extracts of Indonesian medicinal plants A total of 21 samples from 17 species of medicinal plants explored in the East Java region, Indonesia, were used in this study
Ethanol extracts of the plants were examined for antiviral activities against the J6/JFH1-P47 strain of HCV genotype 2a [14] in a cell culture system using Huh7.5 cells at a multiplicity of infection (MOI) of 0.5

Summary

Introduction

Hepatitis C virus (HCV) is a major cause of liver disease and a potential cause of substantial morbidity and mortality worldwide. Current standard treatment using pegylated interferon and ribavirin is effective in only 50% of the patients infected with HCV genotype 1, and is associated with significant side effects. A number of novel antivirals against HCV for clinical use are being tested, it is still of importance to develop complementary and/or alternative drugs for treatment of HCV infection from clinical and economical points of view. In this regard, antiviral substances obtained from natural products, including medicinal plants, are potentially good targets to study [6]

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Conclusion