Triterpenoid Saponins Isolated fromPlatycodon grandiflorumInhibit Hepatitis C Virus Replication

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.

Candidate Genes Involved in the Biosynthesis of Triterpenoid Saponins in Platycodon grandiflorum Identified by Transcriptome Analysis

“…It is a well-known medicinal plant in China and other East Asian countries and has been traditionally used as a medicine and food additive for various respiratory diseases, including bronchitis, asthma, tonsillitis, pulmonary tuberculosis and other inflammatory diseases ( Takagi and Lee, 1972 ; Kim et al, 1995 ; Shin and Lee, 2002 ). Oleanane-type triterpenoid saponins are the main chemical components of P. grandiflorum , mainly including platycodin D, D2, D3, deapioplatycodin D, D2, polygalacin D and platyconic acid A ( Kim J.W. et al, 2013 ).…”

The inhibition of Platycodin D on Mycoplasma pneumoniae proliferation and its effect on promoting cell growth after anti-Mycoplasma pneumoniae treatment

“…Platycodin D was also spermicidal, contraceptive (Lu et al, 2013 ), and anti-atherosclerotic (Wu et al, 2012 ). It has also been reported that platycodin D could be an alternative treatment of obesity by down-regulating lipid accumulation (Lee et al, 2012 ) and that platycodin D was identified as active component with anti-HCV activity (Kim et al, 2013 ). However, there was no report on the anti- M. pneumoniae property of Platycodin D.…”

Influence of sulfur fumigation on glycoside profile in Platycodonis Radix (Jiegeng)

“…Sulfur fumigation was reported to be able to cause chemical changes in herbs [ 16 , 17 ]. In this study, chemical changes were observed in Jiegeng subjected to sulfur fumigation.…”

“…Significant decrease and/or loss of these glycosides caused by sulfur fumigation may negatively affect the bioactivities of Jiegeng . It has been reported that platycodin D, platycodin D 2 and platycodin D 3 have anti-HCV activity [ 17 ]; platycodin D is a potent adjuvant of specific cellular and humoral immune responses against recombinant hepatitis B antigen [ 13 ], and can reduce pancreatic lipase activity significantly [ 18 ]. Whether the decrease in contents of these glycosides during sulfur fumigation will reduce the above mentioned bioactivities of Jiegeng remains to be explored.…”