title: Preclinical development of the green tea catechin, epigallocatechin gallate, as an HIV-1 therapy.
abstract: BACKGROUND
  Previously, we presented evidence that at physiologic concentrations the green tea catechin, epigallocatechin gallate (EGCG), inhibited attachment of HIV-1 glycoprotein 120 to the CD4 molecule on T cells, but the downstream effects of EGCG on HIV-1 infectivity were not determined.
  
  
  OBJECTIVE
  To evaluate the inhibition of HIV-1 infectivity by EGCG and begin preclinical development of EGCG as a possible therapy.
  
  
  METHODS
  PBMCs, CD4(+) T cells, and macrophages were isolated from blood of HIV-1-uninfected donors. HIV-1 infectivity was assessed by an HIV-1 p24 ELISA. Cell survival was assessed by cell viability by Trypan blue exclusion assay, cell growth by thymidine incorporation, and apoptosis by flow-cytometric analysis of annexin-V binding.
  
  
  RESULTS
  Epigallocatechin gallate inhibited HIV-1 infectivity on human CD4(+) T cells and macrophages in a dose-dependent manner. At a physiologic concentration of 6 mumol/L, EGCG significantly inhibited HIV-1 p24 antigen production across a broad spectrum of both HIV-1 clinical isolates and laboratory-adapted subtypes (B [P < .001], C, D, and G [P < .01]). The specificity of the EGCG-induced inhibition was substantiated by the failure of EGCG derivatives lacking galloyl and/or pyrogallol side groups to alter HIV-1 p24 levels. EGCG-induced inhibition of HV-1 infectivity was not a result of cytotoxicity, cell growth inhibition, or apoptosis.
  
  
  CONCLUSIONS
  We conclude that by preventing the attachment of HIV-1-glycoprotein 120 to the CD4 molecule, EGCG inhibits HIV-1 infectivity. Because this inhibition can be achieved at physiologic concentrations, the natural anti-HIV agent EGCG is a candidate as an alternative therapy in HIV-1 therapy.
authors.affiliation: Department of Pediatrics, Baylor College of Medicine and Texas Children's Hospital, Houston, Tex, USA.
authors.forename: Christina L
authors.initials: CL
authors.lastname: Nance
authors.forename: Edward B
authors.initials: EB
authors.lastname: Siwak
authors.forename: William T
authors.initials: WT
authors.lastname: Shearer
mesh_terms: D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects; D028241:Camellia sinensis / Q000737:chemistry*; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016655:HIV Core Protein p24 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1 / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008264:Macrophages / Q000187:drug effects / Q000502:physiology
chemical_list: D000975:Antioxidants; D016655:HIV Core Protein p24; D002392:Catechin; C045651:epigallocatechin gallate