TY - JOUR
T1 - Antiviral activities of Indonesian medicinal plants in the East Java region against hepatitis C virus
AU - Wahyuni, Tutik Sri
AU - Tumewu, Lydia
AU - Permanasari, Adita Ayu
AU - Apriani, Evhy
AU - Adianti, Myrna
AU - Rahman, Abdul
AU - Widyawaruyanti, Aty
AU - Lusida, Maria Inge
AU - Fuad, Achmad
AU - Soetjipto,
AU - Nasronudin,
AU - Fuchino, Hiroyuki
AU - Kawahara, Nobuo
AU - Shoji, Ikuo
AU - Deng, Lin
AU - Aoki, Chie
AU - Hotta, Hak
N1 - Funding Information:
The authors are grateful to Dr. C. M. Rice (The Rockefeller University, New York, NY) for providing Huh-7.5 cells and pFL-J6/JFH1 for the HCV genotype 2a. Thanks are also due to Dr. T. Wakita (National Institute of Infectious Diseases, Tokyo, Japan) for providing pFL-JFH1 and Dr. J. Bukh (Copenhagen University Hospital, Hvidovre, Denmark) for providing the plasmids for the other HCV genotypes; pH77C/JFH1 (1a), pJ4/JFH1 (1b), pJ8/JFH1 (2b), pS52/ JFH1 (3a), pED43/JFH1 (4a), pSA13/JFH1 (5a), pHK6a/JFH1 (6a) and pQC69/ JFH1 (7a). This study was supported in part by Science and Technology Research Partnerships for Sustainable Development (SATREPS) from Japan Science and Technology Agency (JST), Japan International Cooperation Agency (JICA) and the Ministry of Research and Technology (RISTEK), Republic of Indonesia. This study was also carried out as part of Japan Initiative for Global Research Network on Infectious Diseases (J-GRID), Ministry of Education, Culture, Sports, Science and Technology, Japan, and the Global Center of Excellence (G-COE) Program at Kobe University Graduate School of Medicine.
Publisher Copyright:
© 2013 Wahyuni et al.
PY - 2013/8/13
Y1 - 2013/8/13
N2 - Background: Hepatitis 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. Methods: Ethanol 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). Results: Four 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. Conclusions: Ethanol 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.
AB - Background: Hepatitis 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. Methods: Ethanol 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). Results: Four 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. Conclusions: Ethanol 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.
KW - Antiviral activity
KW - Entry inhibition
KW - HCV
KW - Hepatitis C virus
KW - Indonesia
KW - Medicinal plants
UR - http://www.scopus.com/inward/record.url?scp=84881305499&partnerID=8YFLogxK
U2 - 10.1186/1743-422X-10-259
DO - 10.1186/1743-422X-10-259
M3 - Article
C2 - 24089993
AN - SCOPUS:84881305499
SN - 1743-422X
VL - 10
JO - Virology Journal
JF - Virology Journal
IS - 1
M1 - 2247
ER -
