Antiviral activity of ginsenoside Rg3 isomers against gammaherpesvirus through inhibition of p38- and JNK-associated pathways

Natural compounds from functional foods targeting viruses are considered to have important role for regulating virus-related diseases. Ginsenoside Rg3 is one of the active pharmaceutical components found in Panax ginseng C.A. Meyer which is widely used as a functional food in East Asia. In our present study, we have characterized the antiviral activities of the ginsenoside Rg3 isomers, 20(R)- and 20(S)-ginsenoside Rg3, against murine gammaherpesvirus 68 (MHV-68), a mouse model of human gammaherpesvirus which can cause various malignancies including cancer. We found that both 20(R)- and 20(S)-ginsenoside Rg3 inhibited lytic replication and viral proliferation of MHV-68, although 20(S)-ginsenoside Rg3 was more effective than 20(R)-ginsenoside Rg3. Furthermore, ginsenoside Rg3 isomers efficiently repressed chemically-induced lytic replication of human gammaherpesviruses in EBV-positive BC-3 and KSHV-positive Raji cell lines. Finally, our data showed that ginsenoside Rg3 isomers suppressed the p38 and/or the JNK-associated MAPK signaling pathways, thereby inhibiting viral replication.