Ginsenoside Rb1 Eliminates HIV-1 (D3)-Transduced Cytoprotective Human Macrophages by Inhibiting the AKT Pathway

Acquired immunodeficiency syndrome patients treated with red ginseng, which contains protopanxadiol and protopanaxatriol ginsenosides as its main constituents, have been reported to remain healthy for > 20 years in the absence of highly active antiretroviral therapy. Of these ginsenosides, ginsenoside Rh1, a protopanaxatriol ginsenoside, is known to eliminate cytoprotective HIV-1-infected macrophages by inhibiting pyruvate dehydrogenase lipoamide kinase isozyme 1 (PDK-1) phosphorylation. In this study, we investigated the capacity of ginsenoside Rb1, a protopanaxadiol ginsenoside, to eliminate cytoprotective primary human macrophages. We found that ginsenoside Rb1 could also eliminate cytoprotective primary human macrophages infected with HIV-1 D3. Ginsenoside Rb1 inhibited lipopolysaccharide/cycloheximide-induced AKT and glycogen synthase kinase-3 beta phosphorylation in the D3-transduced macrophages, but not the phosphorylation of PDK-1 and phosphoinositide-3-kinase (PI3K). Furthermore, we also observed that a combined treatment with ginsenoside Rb1 and miltefosine synergistically abolished the cytoprotective CHME5 cells expressing HIV-1 tat. Based on these findings, we can conclude that ginsenoside Rb1 can eliminate cytoprotective macrophages infected with HIV-1 by inhibiting the AKT pathway.