Ginsenoside Rh1 could possibly eliminate HIV-1 infected macrophages by inhibiting the PDK1/Akt pathway. - GreenMedInfo Summary

Red ginseng (the steamed root of Panax ginseng C.A. MEYER, Araliaceae), which contains ginsenosides as its main constituents, is frequently used to treat tumor, inflammation, diabetes, stress and acquired immunodeficiency syndrome in Asian countries. Of these ginsenosides, only protopanaxadiol compound K has been reported to abolish the cytoprotective phenotype of human immunodeficiency virus type 1 (HIV-1)-transfected human macrophages. Here, we investigated the anti-cytoprotective effect of protopanaxatriol ginsenoside Rh1 on Tat-expressing cytoprotective CHME5 cells and D3-infected human primary macrophages. Treatment with ginsenoside Rh1 in the presence of lipopolysaccharide/cycloheximide (LPS/CHX) potently abolished the cytoprotective phenotype of Tat-transduced CHME5 cells as well as D3-infected human primary macrophages. Ginsenoside Rh1 significantly inhibited LPS/CHX-induced Akt phosphorylation, as well as mammalian target of rapamycin and Bcl-2-associated death promoter activation in both cell types. Furthermore, ginsenoside Rh1 inhibited pyruvate dehydrogenase lipoamide kinase isozyme 1 (PDK-1) phosphorylation. However, ginsenoside Rh1 did not inhibit phosphoinositide 3-kinase phosphorylation. Ginsenosides Rh1 in the presence of miltefosine (5 µM) additively increased the anti-cytoprotective activity against HIV-1 Tat-expressing macrophages. On the basis of these findings, we propose that ginsenoside Rh1 could possibly eliminate HIV-1 infected macrophages by inhibiting the PDK1/Akt pathway.