Abstract
Hepatitis C virus (HCV) infection is a major cause of liver disease, including cirrhosis and hepatocellular carcinoma. Due to significant adverse effects and emergence of resistant strains of currently developed anti-HCV agents, plant extracts have been considered to be potential sources of new bioactive compounds against HCV. The aim of this study was to evaluate the functional effects of triterpenoid saponins contained in the root extract of Platycodon grandiflorum (PG) on viral enzyme activities and replication in both HCV replicon cells and cell culture grown HCV- (HCVcc-) infected cells. Inhibitory activities of triterpenoid saponins from PG were verified by NS5B RNA-dependent RNA polymerase assay and were further confirmed in the context of HCV replication. Six triterpenoid saponins (platycodin D, platycodin D2, platycodin D3, deapioplatycodin D, deapioplatycodin D2, and platyconic acid A), PG saponin mixture (PGSM), were identified as active components exerting anti-HCV activity. Importantly, PGSM exerted synergistic anti-HCV activity in combination with either interferon-α or NS5A inhibitors. We demonstrated that combinatorial treatment of PGSM and IFN-α efficiently suppressed colony formation with significant reduction in drug resistant variant of HCV. These data suggest that triterpenoid saponin may represent a novel anti-HCV therapeutic agent.
Highlights
Hepatitis C virus (HCV) currently affects nearly 170 million people worldwide, and 3-4 million people are newly infected each year
Cell lysates harvested at two days after PG saponin mixture (PGSM) treatment were immunoblotted with anti-NS5A antibody
We demonstrated that intracellular HCV RNA levels were significantly reduced by treatment of 2 μg of PGSM (Figure 1(b))
Summary
Hepatitis C virus (HCV) currently affects nearly 170 million people worldwide, and 3-4 million people are newly infected each year. The majority of these individuals will be chronically infected and may lead to fibrosis, cirrhosis, and hepatocellular carcinoma [1]. Therapeutic strategy using viral proteins is not fully successful due to error prone nature of HCV RNA replication. For these reasons, there is an urgent need to develop additional therapies that are less toxic, and inexpensive and result in higher sustained virological response (SVR) either as combination or replacement therapies. Discovery of a potent drug candidate from natural products would be useful in overcoming side effects and in generating more synergistic activity
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