Despite remarkable advances in combination antiretroviral therapy (cART), human immunodeficiency virus type 1 (HIV-1) infection remains incurable due to the incomplete elimination of the replication-competent virus, which persists in latent reservoirs. Strategies for targeting HIV reservoirs for eradication that involves reactivation of latent proviruses while protecting uninfected cells by cART are urgently needed for cure of HIV infection. We screened medicinal plant extracts for compounds that could reactivate the latent HIV-1 provirus and identified a procyanidin trimer Cl derived from Theobroma cacao as a potent activator of the provirus in human T cells latently infected with HIV-1. This reactivation largely depends on the NF-kappa B and MAPK signaling pathways because either overexpression of a super-repressor form of I kappa B alpha or pretreatment with a MEK inhibitor U0126 diminished provirus reactivation by Cl. A pan-PKC inhibitor significantly blocked the phorbol ester-induced but not the Cl-induced HIV-1 reactivation. Although Cl-induced viral gene expression persisted for as long as 48 h post-stimulation, NF-kappa B-dependent transcription peaked at 12 h post-stimulation and then quickly declined, suggesting Tat-mediated self-sustainment of HIV-1 expression. These results suggest that procyanidin Cl trimer is a potential compound for reactivation of latent HIV-1 reservoirs. (C) 2015 Elsevier Inc. All rights reserved.