Selected ginsenosides interfere efficiently with hepatitis B virus mRNA expression levels and suppress viral surface antigen secretion
Ganesh Selvaraj Duraisamy,
Eunji Jo,
Ivana Huvarová,
Kyu-Ho P. Park,
Zbyněk Heger,
Vojtěch Adam,
Daniel Růžek,
Marc P. Windisch,
Andrew D. Miller
Affiliations
Ganesh Selvaraj Duraisamy
Veterinary Research Institute, Hudcova 296/70, CZ-621 00, Brno, Czech Republic
Eunji Jo
Applied Molecular Virology Laboratory, Institut Pasteur Korea, 696 Sampyeong-dong, Bundang-gu, Seongnam-si, Gyeonggi-do, South Korea
Ivana Huvarová
Veterinary Research Institute, Hudcova 296/70, CZ-621 00, Brno, Czech Republic
Kyu-Ho P. Park
Screening Discovery Platform, Institut Pasteur Korea, 696 Sampyeong-dong, Bundang-gu, Seongnam-si, Gyeonggi-do, South Korea
Zbyněk Heger
Department of Chemistry and Biochemistry, Mendel University in Brno, Zemědělská 1665/1, CZ-613 00, Brno, Czech Republic
Vojtěch Adam
Department of Chemistry and Biochemistry, Mendel University in Brno, Zemědělská 1665/1, CZ-613 00, Brno, Czech Republic
Daniel Růžek
Veterinary Research Institute, Hudcova 296/70, CZ-621 00, Brno, Czech Republic; Institute of Parasitology, Biology Centre of the Czech Academy of Sciences, Branišovská 1160/31, CZ-370 05, České Budějovice, Czech Republic; Department of Experimental Biology, Faculty of Science, Masaryk University, Kamenice 735/5, CZ-625 00, Brno, Czech Republic
Marc P. Windisch
Applied Molecular Virology Laboratory, Institut Pasteur Korea, 696 Sampyeong-dong, Bundang-gu, Seongnam-si, Gyeonggi-do, South Korea; Division of Bio-Medical Science and Technology, University of Science and Technology, Daejeon, South Korea; Corresponding author.
Andrew D. Miller
Veterinary Research Institute, Hudcova 296/70, CZ-621 00, Brno, Czech Republic; Department of Chemistry and Biochemistry, Mendel University in Brno, Zemědělská 1665/1, CZ-613 00, Brno, Czech Republic; KP Therapeutics (Europe) s.r.o., Purkyňova 649/127, CZ-612 00, Brno, Czech Republic; Corresponding author.
Ginsenosides are a class of natural steroid glycosides and triterpene saponins found in Panax ginseng. After screening of a commercial ginsenoside compound library for low cellular cytotoxicity and the ability to mediate efficient reductions in hepatitis B virus (HBV) mRNA expression levels in HepG2.2.15 cells, three ginsenosides (Rg6, Rh4, and Rb3) are selected. Thereafter, using the same cellular model, all three ginsenosides are shown to mediate efficient, selective inhibition of HBV mRNA expression levels, and also interfere with the secretion of both HBV particles and hepatitis B surface antigen (HBsAg). Drug combination studies are performed in both HepG2.2.15 and HBV-infected HepG2-NTCPsec+ cell models with the selected ginsenosides and lamivudine (LMV), a nucleoside analogue used to treat chronic hepatitis B (CHB) infections. These studies, involving RT-qPCR and ELISA, suggest that Rh4/LMV combinations in particular act synergistically to inhibit the secretion of HBV particles and HBsAg. Therefore, on the assumption that appropriate in vivo data are in future agreement, Rh4, in particular, might be used in combination with nucleoside/nucleotide analogues (NUCs) to devise an effective, cost-efficient combination therapy for the treatment of patients with CHB infections.
