Vol 11, Issue 2, 2018 Online - 2455-3891 Print - 0974-2441 ANTIHEPATITIS C VIRUS ACTIVITY OF INDONESIAN MAHOGANY (TOONA SURENI) ACHMAD FUAD HAFID 1,2 *, TUTIK SRI WAHYUNI 1,2 , LIDYA TUMEWU 1 , EVHY APRYANI 1 , ADITA AYU PERMANASARI 1 , MYRNA ADIANTI 1,3 , CHIE AOKI UTSUBO 4 , ATY WIDYAWARUYANTI 1,2 , MARIA INGE LUSIDA 1 , SOETJIPTO 1 , HIROYUKI FUCHINO 6 , NOBUO KAWAHARA 6 , HAK HOTTA 5 1 Institute of Tropical Disease, Universitas Airlangga, Surabaya, Indonesia. 2 Department of Pharmacognosy and Phytochemistry, Faculty of Pharmacy, Universitas Airlangga, Surabaya, Indonesia. 3 Department of Health, Study Program Traditional Medicine, Vocational Faculty, Universitas Airlangga, Surabaya, Indonesia. 4 Department of International Health, Kobe University Graduate School of Health Sciences, 7-10-2, Tomogaoka, Suma-ku, Kobe 654-0142, Japan. 5 Department of Oral Vaccine and Drug Development, Kobe University Graduate School of Health Sciences, 1-5-6 Minatojima-minamimachi, Chou-ku, Kobe 650-0047, Japan. 6 Research Center for Medicinal Plant Resources, National Institute of Biomedical Innovation, Tsukuba, Ibaraki, Japan. Email: achmadfuad@ff.unair.ac.id, achmadfuad@yahoo.com Received: 24 February 2017, Revised and Accepted: 27 October 2017 ABSTRACT Objective: Toona sureni (Indonesian mahogany) is a member of Meliaceae family and locally known as suren. Previous study reported that T. sureni leaves extract exhibited antiviral activity with 50% inhibitory concentration (IC 50 ) value of 13.9 ± 1.6 µg/ml against hepatitis C virus (HCV) J6/JFH1. Cytotoxicity analysis of T. sureni leaves extract did not reveal any cytotoxicity effect; therefore, further study was taken to investigate the active substances from the extract. Methods: Bioassay-guided isolation of anti-HCV was conducted using Huh-7.5 cells infected with HCV J6/JFH1 in the presence of extracts, fractions, or compounds from the plant. Results: Ethyl acetate fraction (Fr E) exhibited high anti-HCV activity with IC 50 value of 1.7 µg/ml. Further, separation of Fr E by open column chromatography resulted in nine sub-fractions (sub-Fr E1-E9). Sub-Fr E3 and E4 have IC 50 value of 29.90 µg/ml and 7.68 µg/ml, respectively. Polyphenols compounds have been isolated from sub-Fr E3 and E4. The structures have been determined to be ethyl gallate (1), methyl gallate (2), catechin (3), gallic acid (4), and quercetin 3-O-rhamnoside (5). Among the isolated compounds, gallic acid showed to possess strong anti-HCV activity with IC 50 value of 15.9 µg/ml. Conclusion: T. sureni and its isolated compound, gallic acid, may be good candidates to develop for alternative and/or complementary agents of anti-HCV infection. Keywords: Toona sureni, Leaves extract, Polyphenols, Antihepatitis C virus, Gallic acid. INTRODUCTION Hepatitis C virus (HCV) is a major cause of liver disease and potential cause of substantial morbidity and mortality worldwide. Global prevention and control of HCV were met with difficulties due to the complexity and uncertainty related to the geographic distribution of HCV infection and chronic hepatitis C, determination of its associated risk factors, and evaluation of cofactors that accelerate its progression. No vaccine is available to prevent HCV infection, nor does immune globulin provide protection [1,2]. Hepatitis C is an RNA virus that mutates very rapidly, until now, there were seven genotypes (1–7) with more than 70 subtypes. HCV genome encodes structural protein (Core, E1, and E2) and non-structural protein (NS2, NS3, NS4A, NS4B, NS5A, and NS5B). Glycoproteins E1 and E2 were responsible for virus binding to the cell surface meanwhile the function of non-structural protein was RNA replication and virus particle construction [3-5]. The current standard interferon-free treatment regimens with a combination of direct-acting antiviral agents (DAAs) targeting the viral NS3 protease, NS5A multifunction protein, and NS5B RNA-dependent RNA polymerase result sustained virological responses >90%. However, the emergence of DAA-resistant HCV strains, limited access to the DAAs due to their high cost is also an important issue. Many therapies for HCV infection have been developed, but the therapeutic efficacy still needs to be improved [6]. In future, anti-HCV research should aim at the development of therapies for non-responder patient population and treatment regiments with short duration of treatment [7]. Many plants species are being tested for anti-HCV to find a possible cure for HCV. Some of them have shown significant inhibition in entry, replication, and assembly steps of the viral life cycle [8]. Moreover, some compounds have been isolated and tested for anti-HCV. Previous study reported that chalepin and pseudane IX which isolated from Ruta angustifolia leaves showed strong anti-HCV activities with 50% inhibitory concentration (IC 50 ) value of 1.7 ± 0.5 and 1.4 ± 0.2 µg/ml, respectively, without apparent cytotoxicity [9]. A major catabolite of chlorophyll A, which was isolated from Morinda citrifolia and identified as pheophorbide A, was reported to possess anti-HCV activity with IC 50 value of 0.3 µg/ml. It was reported also that pyropheophorbide A is an anti-HCV compound with IC 50 value of 0.2 µg/ml [10]. Adianti et al. suggested that glycycoumarin, glycerin, glycerol, and liquiritigenin isolated from Glycyrrhiza uralensis, as well as isoliquiritigenin, licochalcone A, and glabridin, would be good candidates for seed compounds to develop antivirals against HCV [11]. Quercetin and gallic acid isolated from Kalanchoe pinnata inhibited HCV production in a dose-dependent manner with IC 50 value of 1.5 and 6.1 µg/ml, respectively, without exhibiting cytotoxicity [12]. © 2018 The Authors. Published by Innovare Academic Sciences Pvt Ltd. This is an open access article under the CC BY license (http://creativecommons. org/licenses/by/4. 0/) DOI: http://dx.doi.org/10.22159/ajpcr.2018.v11i2.18126 Research Article