Abstract
Saponins are a group of naturally occurring plant glycosides which possess a wide range of pharmacological properties, including anti-tumorigenic and antiviral activities. To investigate whether saponin has anti-hepatitis C virus (HCV) activity, we examined the effect of saponin on HCV replication. HCV replication was efficiently inhibited at a concentration of 10 µg/ml of saponin in cell culture grown HCV (HCVcc)-infected cells. Inhibitory effect of saponin on HCV replication was verified by quantitative real-time PCR, reporter assay, and immunoblot analysis. In addition, saponin potentiated IFN-α-induced anti-HCV activity. Moreover, saponin exerted antiviral activity even in IFN-α resistant mutant HCVcc-infected cells. To investigate how cellular genes were regulated by saponin, we performed microarray analysis using HCVcc-infected cells. We demonstrated that suppressor of cytokine signaling 2 (SOCS2) protein level was distinctively increased by saponin, which in turn resulted in inhibition of HCV replication. We further showed that silencing of SOCS2 resurrected HCV replication and overexpression of SOCS2 suppressed HCV replication. These data imply that saponin inhibits HCV replication via SOCS2 signaling pathway. These findings suggest that saponin may be a potent therapeutic agent for HCV patients.
Highlights
Hepatitis C virus (HCV) is a major cause for chronic liver disease leading to liver cirrhosis and hepatocellular carcinoma (HCC) [1]
We found that 20 mg/ml of saponin exerted no cytotoxicity in HCVcc-infected cells
Because suppressor of cytokine signaling 2 (SOCS2) has been implicated in the negative regulation of cytokine signal transduction pathway, we investigated whether SOCS2 was involved in saponin-mediated inhibition of HCV replication
Summary
Hepatitis C virus (HCV) is a major cause for chronic liver disease leading to liver cirrhosis and hepatocellular carcinoma (HCC) [1]. A vaccine is not yet available and the only licensed therapy for patients infected with HCV is a combination of the pegylated interferon (IFN)-a and ribavirin. The therapy with these agents is associated with various adverse effects and achieves a sustained virological response (SVR) with significant differences among genotypes [5]. Two inhibitors of HCV protease, boceprevir (VictrelisTM) and telaprevir (IncivekTM), are recently approved by the Food and Drug Administration, these drugs are only effective in combination with peginterferon alpha and ribavirin. Hussein et al reported that medicinal plant extracts from Acacia nilotica, Boswellia carterii, Embelia schimperi, Piper cubeba, Quercus infectoria, Trachyspermum ammi, and Syzygium aromaticum significantly inhibited HCV protease activity in vitro [10]
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