Chromatin　remodeling,　especially　in　relation　to　the　transactivator　Tat,　is　an　essential　event　for　human　immunodeficiency　virus-1　(HIV-1)　transcription.　Curcumin　has　been　shown　to　suppress　pathways　linked　to　HIV-1　replication.　We　investigated　whether　curcumin　had　the　potential　to　inhibit　Tat-induced　long　terminal　repeat　region　(LTR)　transactivation.　As　we　shown,　curcumin　inhibited　Tat-induced　LTR　transcativation,　while　knockdown　of　histone　deacetylase　1　(HDAC1)　by　siRNA　potentiated　Tat-induced　HIV-1　transcativation.　Curcumin　reversed　Tat-induced　down-regulation　of　HDAC1　expression　in　multinuclear　activation　of　galactosidase　indicator　(MAGI)　cells.　Treatment　with　curcumin　reversed　Tat-induced　dissociation　of　HDAC1　from　LTR;　and　curcumin　caused　a　decline　in　the　binding　of　p65/NF　kappa　B　to　LTR　promoters　stimulated　by　Tat.　Curcumin　attenuated　Tat-induced　p65　phosphorylation　and　IKK　phosphorylation.　Curcumin　reversed　Tat-mediated　reduction　in　AMPK　activation　and　downstream　acetyl-CoA　carboxylase　(ACC)　activation.　Collectively,　our　data　provide　new　insights　into　understanding　of　the　molecular　mechanisms　of　curcumin　inhibited　Tat-regulated　transcription,　suggesting　that　targeting　AMPK/HDAC1/NF　kappa　B　pathway　could　serve　as　new　anti-HIV-1　agents.　J.　Cell.　Physiol.　226:　3385-3391,　2011.　(C)　2011　Wiley　Periodicals,　Inc.