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.

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