Tat　transactivating　activity　regulated　by　NAD+-dependent　histone　deacetylase　sirtuin1　(SIRT1)　connects　HIV　transcription　with　the　metabolic　state　of　the　cell.　Nicotinamide　phosphoribosyltransferase　(Nampt)　is　a　rate-limiting　enzyme　in　the　mammalian　NAD+　biosynthesis.　Nampt,　SIRT1,　and　AMPK　were　involved　in　inhibiting　HIV-1　transactivation　through　redox-regulated　pathway.　Tanshinone　II　A　is　a　main　lipid-soluble　monomer　derivative　from　the　root　of　Salvia　miltiorrhiza　(Danshen)　and　tanshinone　II　A　possess　a　variety　of　biological　activities　through　redox　signaling　pathway.　Here　we　investigated　the　effect　of　tanshinone　II　A　on　Tat-induced　HIV-1　transactivation　and　the　redox　signaling　pathway　involved　in　it.　As　the　results　were　shown,　tanshinone　II　A　reversed　Tat-induced　reactive　oxygen　species　(ROS)　production　and　down-regulation　of　glutathione　(GSH)　levels　in　TZM-bl　cells　through　up-regulation　of　Nrf2　expression.　Tanshinone　II　A　reversed　Tat-induced　inhibition　of　SIRT1　activity　but　not　SIRT1　protein　expression.　Tanshinone　II　A　reversed　Tat-induced　inhibition　of　Nampt　protein　expression　and　depletion　of　NAD+　levels　in　TZM-bl　cells　in　a　dose-dependent　manner.　Tanshinone　II　A-evoked　Nampt　expression　was　mediated　by　AMPK　signaling　pathway.　Tanshinone　II　A　inhibited　Tat-induced　HIV-1　LTR　transactivation　dependent　on　AMPK-Nampt　pathway.　Collectively,　our　data　provide　new　insights　into　understanding　of　the　molecular　mechanisms　of　tanshinone　II　A　inhibited　Tat-regulated　transcription,　suggesting　that　targeting　AMPK/Nampt/SIRT1　pathway　could　serve　as　new　anti-HIV-1　agents.　J.　Cell.　Physiol.　229:　1193-1201,　2014.　(c)　2014　Wiley　Periodicals,　Inc.