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

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 mg/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 mg/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 mg/mL, respectively. Another chalcone, isoliquiritigenin, also showed anti-HCV activity, with an IC 50 of 3.7 mg/mL. Time-ofaddition 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.

Isoliquiritigenin Inhibits Interferon-γ-Inducible Genes Expression in Hepatocytes through Down-Regulating Activation of JAK1/STAT1, IRF3/MyD88, ERK/MAPK, JNK/MAPK and PI3K/Akt Signaling Pathways

“…Many previous studies have demonstrated its variety of biological functions, such as anti-inflammatory [27], anti-oxidative [26], chemopreventive activities [29], and anti-platelet aggregation properties [28], and so on. Also, ISL has been reported to suppress replication of HCV in a dose-dependent manner [35]. IFN-γ/JAKs/ STAT1 pathway is the classical pathway to regulate IFN-inducible genes expression, and several studies showed that the expression of CXCL9-10 was induced via the activation of JAK1, JAK2/STAT1 [36].…”

Inhibition of hepatitis C virus replication by chalepin and pseudane IX isolated from Ruta angustifolia leaves

“…We tested ethanol extracts of Indonesia plants for their anti-HCV activities and reported that Toona sureni leaves, Melicope latifolia leaves, Melanolepis multiglandulosa stem and Ficus fistulosa leaves possessed anti-HCV activities [10]. We also reported that extracts of Glycyrrhiza uralensis root and isolated compounds, such as glycycoumarin, glycerin, glycyrol, and liquiritigenin, and extracts of Morinda citrifolia leaves, an isolated compound, pheophorbide a, and its related compound, pyropheophorbide a, exhibited anti-HCV activities [11,12]. Likewise, silymarin, iridoid, epigallocatechin-3-gallate were reported to inhibit HCV infection at the entry step while diosgenin, luteolin, quercetin, 3-hydroxy caruilignan C, excoecariphenol D and apigenin at the post-entry step [13,14].…”

“…Time-of-addition experiments were performed to assess the mode of action of the samples, as described previously [10][11][12]. In brief, three sets of experiments were done in parallel.…”

Antihepatitis C Virus Activity of Indonesian Mahogany (Toona Sureni)

“…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].…”