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      Anti‐hepatitis C virus compounds obtained from Glycyrrhiza uralensis and other Glycyrrhiza species

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          ABSTRACT

          Development of complementary and/or alternative drugs for treatment of hepatitis C virus (HCV) infection is still much needed from clinical and economic points of view. Antiviral substances obtained from medicinal plants are potentially good targets to study. Glycyrrhiza uralensis and G. glabra have been commonly used in both traditional and modern medicine. In this study, extracts of G. uralensis roots and their components were examined for anti‐HCV activity using an HCV cell culture system. It was found that a methanol extract of G. uralensis roots and its chloroform fraction possess anti‐HCV activity with 50%‐inhibitory concentrations (IC 50) of 20.0 and 8.0 μg/mL, respectively. Through bioactivity‐guided purification and structural analysis, glycycoumarin, glycyrin, glycyrol and liquiritigenin were isolated and identified as anti‐HCV compounds, their IC 50 being 8.8, 7.2, 4.6 and 16.4 μg/mL, respectively. However, glycyrrhizin, the major constituent of G. uralensis, and its monoammonium salt, showed only marginal anti‐HCV activity. It was also found that licochalcone A and glabridin, known to be exclusive constituents of G. inflata and G. glabra, respectively, did have anti‐HCV activity, their IC 50 being 2.5 and 6.2 μg/mL, respectively. Another chalcone, isoliquiritigenin, also showed anti‐HCV activity, with an IC 50 of 3.7 μg/mL. Time‐of‐addition analysis revealed that all Glycyrrhiza‐derived anti‐HCV compounds tested in this study act at the post‐entry step. In conclusion, the present results suggest that glycycoumarin, glycyrin, glycyrol and liquiritigenin isolated from G. uralensis, as well as isoliquiritigenin, licochalcone A and glabridin, would be good candidates for seed compounds to develop antivirals against HCV.

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          Most cited references30

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          Global epidemiology of hepatitis C virus infection: new estimates of age-specific antibody to HCV seroprevalence.

          In efforts to inform public health decision makers, the Global Burden of Diseases, Injuries, and Risk Factors 2010 (GBD2010) Study aims to estimate the burden of disease using available parameters. This study was conducted to collect and analyze available prevalence data to be used for estimating the hepatitis C virus (HCV) burden of disease. In this systematic review, antibody to HCV (anti-HCV) seroprevalence data from 232 articles were pooled to estimate age-specific seroprevalence curves in 1990 and 2005, and to produce age-standardized prevalence estimates for each of 21 GBD regions using a model-based meta-analysis. This review finds that globally the prevalence and number of people with anti-HCV has increased from 2.3% (95% uncertainty interval [UI]: 2.1%-2.5%) to 2.8% (95% UI: 2.6%-3.1%) and >122 million to >185 million between 1990 and 2005. Central and East Asia and North Africa/Middle East are estimated to have high prevalence (>3.5%); South and Southeast Asia, sub-Saharan Africa, Andean, Central, and Southern Latin America, Caribbean, Oceania, Australasia, and Central, Eastern, and Western Europe have moderate prevalence (1.5%-3.5%); whereas Asia Pacific, Tropical Latin America, and North America have low prevalence (<1.5%). The high prevalence of global HCV infection necessitates renewed efforts in primary prevention, including vaccine development, as well as new approaches to secondary and tertiary prevention to reduce the burden of chronic liver disease and to improve survival for those who already have evidence of liver disease. Copyright © 2012 American Association for the Study of Liver Diseases.
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            Review of Pharmacological Effects of Glycyrrhiza sp. and its Bioactive Compounds

            Abstract The roots and rhizomes of licorice (Glycyrrhiza) species have long been used worldwide as a herbal medicine and natural sweetener. Licorice root is a traditional medicine used mainly for the treatment of peptic ulcer, hepatitis C, and pulmonary and skin diseases, although clinical and experimental studies suggest that it has several other useful pharmacological properties such as antiinflammatory, antiviral, antimicrobial, antioxidative, anticancer activities, immunomodulatory, hepatoprotective and cardioprotective effects. A large number of components have been isolated from licorice, including triterpene saponins, flavonoids, isoflavonoids and chalcones, with glycyrrhizic acid normally being considered to be the main biologically active component. This review summarizes the phytochemical, pharmacological and pharmacokinetics data, together with the clinical and adverse effects of licorice and its bioactive components. Copyright © 2008 John Wiley & Sons, Ltd.
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              Development and characterization of hepatitis C virus genotype 1-7 cell culture systems: role of CD81 and scavenger receptor class B type I and effect of antiviral drugs.

              Six major hepatitis C virus (HCV) genotypes and numerous subtypes have been described, and recently a seventh major genotype was discovered. Genotypes show significant molecular and clinical differences, such as differential response to combination therapy with interferon-alpha and ribavirin. Recently, HCV research has been accelerated by cell culture systems based on the unique growth capacity of strain JFH1 (genotype 2a). By development of JFH1-based intergenotypic recombinants containing Core, envelope protein 1 and 2 (E1, E2), p7, and nonstructural protein 2 (NS2) of genotype 6a and 7a strains, as well as subtype 1b and 2b strains, we have completed a panel of culture systems for all major HCV genotypes. Efficient growth in Huh7.5 cells depended on adaptive mutations for HK6a/JFH1 (6a/2a, in E1 and E2) and J4/JFH1 (1b/2a, in NS2 and NS3); viability of J8/JFH1 (2b/2a) and QC69/JFH1 (7a/2a) did not require adaptation. To facilitate comparative studies, we generated virus stocks of genotype 1-7 recombinants with infectivity titers of 10(3.7) to 10(5.2) 50% tissue culture infectious dose/mL and HCV RNA titers of 10(7.0) to 10(7.9) IU/mL. Huh7.5 cultures infected with genotype 1-6 viruses had similar spread kinetics, intracellular Core, NS5A, and lipid amounts, and colocalization of Core and NS5A with lipids. Treatment with interferon-alpha2b but not ribavirin or amantadine showed a significant antiviral effect. Infection with all genotypes could be blocked by specific antibodies against the putative coreceptors CD81 and scavenger receptor class B type I in a dose-dependent manner. Finally, neutralizing antibodies in selected chronic phase HCV sera had differential effects against genotype 1-7 viruses. We completed and characterized a panel of JFH1-based cell culture systems of all seven major HCV genotypes and important subtypes and used these viruses in comparative studies of antivirals, HCV receptor interaction, and neutralizing antibodies.
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                Author and article information

                Journal
                Microbiol Immunol
                Microbiol. Immunol
                10.1111/(ISSN)1348-0421
                MIM
                Microbiology and Immunology
                John Wiley and Sons Inc. (Hoboken )
                0385-5600
                1348-0421
                March 2014
                05 March 2014
                : 58
                : 3 ( doiID: 10.1111/mim.v58.3 )
                : 180-187
                Affiliations
                [ 1 ] Division of Microbiology Kobe University Graduate School of Medicine 7‐5‐1 Kusunoki‐cho Chuo‐ku Kobe 650‐0017
                [ 2 ] Institute of Tropical Disease Airlangga University Jl. Mulyorejo Surabaya 60115
                [ 3 ] Japan Science and Technology/Japan International Cooperation Agency Science and Technology Research Partnership for Sustainable Development Laboratory (JST/JICA SATREPS), Faculty of Medicine University of Indonesia Jl. Salemba 4 Jakarta 10430 Indonesia
                [ 4 ] Research Center for Medicinal Plant Resources National Institute of Biomedical Innovation 1–2, Hachimandai Tsukuba City Ibaraki Prefecture 305‐0843 Japan
                Author notes
                [*] [* ] Correspondence

                Hak Hotta, Division of Microbiology, Kobe University Graduate School of Medicine, 7‐5‐1 Kusunoki‐cho, Chuo‐ku, Kobe, 650‐0017, Japan. Tel: +81 78 382 5500; fax: +81 78 382 5519; email: hotta@ 123456kobe-u.ac.jp

                Article
                MIM12127
                10.1111/1348-0421.12127
                7168410
                24397541
                90dbd3f3-ea5c-407a-9f79-ddb961f8756a
                © 2014 The Societies and Wiley Publishing Asia Pty Ltd

                This article is being made freely available through PubMed Central as part of the COVID-19 public health emergency response. It can be used for unrestricted research re-use and analysis in any form or by any means with acknowledgement of the original source, for the duration of the public health emergency.

                Page count
                Pages: 8
                Product
                Categories
                Original Article
                Original Articles
                Virology
                Custom metadata
                2.0
                March 2014
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.8.0 mode:remove_FC converted:15.04.2020

                antiviral substance,coumarin,hepatitis c virus
                antiviral substance, coumarin, hepatitis c virus

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