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

Abstract

Hepatitis C virus (HCV) infection is highly prevalent among global populations, with an estimated number of infected patients being 170 million. Approximately 70-80% of patients acutely infected with HCV will progress to chronic liver disease, such as liver cirrhosis and hepatocellular carcinoma, which is a substantial cause of morbidity and mortality worldwide. New therapies for HCV infection have been developed, however, the therapeutic efficacies still need to be improved. Medicinal plants are promising sources for antivirals against HCV. A variety of plants have been tested and proven to be beneficial as antiviral drug candidates against HCV. In this study, we examined extracts, their subfractions and isolated compounds of Ruta angustifolia leaves for antiviral activities against HCV in cell culture. We isolated six compounds, chalepin, scopoletin, γ-fagarine, arborinine, kokusaginine and pseudane IX. Among them, chalepin and pseudane IX showed strong anti-HCV activities with 50% inhibitory concentration (IC 50 ) of 1.7 ± 0.5 and 1.4 ± 0.2 μg/ml, respectively, without apparent cytotoxicity. Their anti-HCV activities were stronger than that of ribavirin (2.8 ± 0.4 μg/ml), which has been widely used for the treatment of HCV infection. Mode-of-action analyses revealed that chalepin and pseudane IX inhibited HCV at the post-entry step and decreased the levels of HCV RNA replication and viral protein synthesis. We also observed that arborinine, kokusaginine and γ-fagarine possessed moderate levels of anti-HCV activities with IC 50 values being 6.4 ± 0.7, 6.4 ± 1.6 and 20.4 ± 0.4 μg/ml, respectively, whereas scopoletin did not exert significant anti-HCV activities at 30 μg/ml.

Furochinoline alkaloids in plants from Rutaceae family – a review

“…What is more, these compounds were more active than ribavirin, the standard used in treatment. The IC 50 of γ-fagarine (3) was 20.4 μg/ml, but it was 2.8 μg/ml for ribavirin and 6.4 μg/ml for kokusaginine (13) [34].…”

Antiviral Phytochemicals: An Overview

“…To firmly establish the antiviral activity and adverse reactions like reactogenecity or toxicity of the purified phytomolecules, appropriate in vivo studies (animal models) and subsequent clinical trials are necessary. A bioactive flavonoid 'Baicalein' isolated from Chinese medicinal plant Scutellaria baicalensis Georgi showed antiviral properties using high-speed counter-current chromatography (HSCCC) technique [42][43][44][45][46][47][48][49][50][51][52][53][54][55][56][57][58].…”

Antihepatitis C Virus Activity of Indonesian Mahogany (Toona Sureni)

“…Time of addition experiment revealed that the extract inhibited both at the entry and postentry steps. T. sureni leaves extract was not toxic (cytotoxicity concentration [CC 50 ]>500 µg/ml, SI>35.9); therefore, further study was taken to investigate the active substances from T. sureni leaves extract [13].…”

“…The stock solutions were stored at −20°C until they were used. Analysis of anti-HCV method was described previously [9,13]. Huh-7.5 cells were seeded in 24-well plates (cell density 1.9×10 5 cells/well).…”