Reactivation of latent HIV-1in vitrousing an alcoholic extract fromEuphorbia umbellata(Euphorbiaceae) latex

Euphorbia umbellata (E. umbellata)belongs toEuphorbiaceaefamily, popularly known as Janauba, and contains in its latex a combination of phorbol esters with biological activities described to different cellular protein kinase C (PKC) isoforms. Here, we identified deoxi-phorbol esters present inE. umbellatalatex alcoholic extract able to increase HIV transcription and reactivate HIV from latency models. This activity was mediated by NF-kB activation followed by nuclear translocation and binding to HIV LTR promoter. In addition,E. umbellatelatex extract induced the production of pro inflammatory cytokines together with IL21 inin vitrohuman PBMC cultures. Our latex extract activates latent HIV in human PBMCs isolated from HIV positive patients as well as latent SIV in non-human primate primary CD4+T lymphocytes. These results strongly indicate that the phorbol esters present inE. umbellatalatex are promising candidate compounds for future clinical trials forshock and killtherapy to promote HIV cure and eradication.