THE JOURNAL OF PHYSICAL CHEMISTRY

http://pubs.acs.org/journals/jpcbfk/index.html

 

Volume 110, Number 6, Pages 2910-2917 (February 2006)

 

Hamza A, Zhan CG.

 

How can (-)-epigallocatechin gallate from green tea prevent HIV-1 infection? Mechanistic insights from computational modeling and the implication for rational design of anti-HIV-1 entry inhibitors.


Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, Kentucky, USA.


Possible inhibitors preventing human immunodeficiency virus type 1 (HIV-1) entry into the cells are recognized as hopeful next-generation anti-HIV-1 drugs. It is highly desirable to develop a potent inhibitor blocking binding of glycoprotein CD4 of the cell with glycoprotein gp120 of HIV-1, because the gp120-CD4 binding is the initial step of HIV-1 entry into the cells. It has been recently reported that (-)-epigallocatechin gallate (EGCG) from green tea is an inhibitor blocking gp120-CD4 binding. But the inhibitory mechanism remains unknown. For understanding the inhibitory mechanism, extensive molecular docking, molecular dynamics simulations, and binding free-energy calculations have been performed in this study to predict the most favorable structures of CD4-EGCG, gp120-CD4, and gp120-CD4-EGCG binding complexes in water. The results reveal that EGCG binds with CD4 in such a way that the calculated binding affinity of gp120 with the CD4-EGCG complex is negligible. So, the favorable binding of EGCG with CD4 can effectively block gp120-CD4 binding. The calculated CD4-EGCG binding affinity (DeltaG(bind) = -5.5 kcal/mol, K(d) = 94 microM) is in excellent agreement with available experimental data suggesting IC(50) approximately 100 microM for EGCG-blocking CD4-gp120 binding. These results and insights provide a rational basis for future design of novel, more potent inhibitors to block gp120-CD4 binding.

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http://pubs.acs.org/cgi-bin/abstract.cgi/jpcbfk/2006/110/i06/abs/jp0550762.html

 

 

The official journal of Japanese Canser Association

http://www.blackwell-synergy.com/loi/CAS

 

Volume 95, Issue 7, Pages 596-601 (July 2004)

Sonoda J, Koriyama C, Yamamoto S, Kozako T, Li HC, Lema C, Yashiki S, Fujiyoshi T, Yoshinaga M, Nagata Y, Akiba S, Takezaki T, Yamada K, Sonoda S.

 

HTLV-1 provirus load in peripheral blood lymphocytes of HTLV-1 carriers is diminished by green tea drinking.


Department of Clinical Pharmacology, Faculty of Medicine, KagoshimaUniversity, Kagoshima, Japan.


Human T-cell lymphotropic virus type 1 (HTLV-1) is causatively associated with adult T-cell leukemia (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Since a high level of HTLV-1 provirus load in circulating lymphocytes is thought to be a risk for ATL and HAM/TSP, diminution of HTLV-1 provirus load in the circulation may prevent these intractable diseases. Our previous study (Jpn J Cancer Res 2000; 91: 34-40) demonstrated that green tea polyphenols inhibit in vitro growth of ATL cells, as well as HTLV-1-infected T-cells. The present study aimed to investigate the in vivo effect of green tea polyphenols on HTLV-1 provirus load in peripheral blood lymphocytes on HTLV-1 carriers. We recruited 83 asymptomatic HTLV-1 carriers to examine HTLV-1 provirus DNA with or without administration of capsulated green tea extract powder. Thirty-seven subjects were followed up for 5 months by measuring HTLV-1 provirus load after daily intake of 9 capsules of green tea extract powder per day (equivalent to 10 cups of regular green tea), and 46 subjects lived ad libitum without intake of any green tea capsule. The real-time PCR quantification of HTLV-1 DNA revealed a wide range of variation of HTLV-1 provirus load among asymptomatic HTLV-1 carriers (0.2-200.2 copies of HTLV-1 provirus load per 1000 peripheral blood lymphocytes). Daily intake of the capsulated green tea for 5 months significantly diminished the HTLV-1 provirus load as compared with the controls (P = 0.031). These results suggest that green tea drinking suppresses proliferation of HTLV-1-infected lymphocytes in vivo.

 

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http://www.blackwell-synergy.com/doi/pdf/10.1111/j.1349-7006.2004.tb02493.x

 

 

ELSEVIER

Cellular Immunology

Academic Press

http://www.elsevier.com/wps/find/journaldescription.cws_home/622804/description#description

 

 

Volume 237, Issue 1, Pages 7-16 (September 2005)

 

Watson JL, Vicario M, Wang A, Moreto M, McKay DM.

 

Immune cell activation and subsequent epithelial dysfunction by Staphylococcus enterotoxin B is attenuated by the green tea polyphenol (-)-epigallocatechin gallate.

 

Intestinal Disease Research Programme, Department of Pathology and Molecular Medicine, McMaster University, Ontario, Canada.

 

Bacterial superantigens (SAg) are potent T cell activators and when delivered systemically elicit a self-limiting enteropathy in mice. Also, SAg-stimulated human peripheral blood mononuclear cells (PBMC) increase enteric epithelial cell monolayer permeability in vitro. Epigallocatechin gallate (EGCG), the major polyphenol component of green tea (Camilla sinesis) leaf, has been presented as an anti-inflammatory agent. We tested the hypothesis that EGCG (10-100 microM) would block PBMC activation by the SAg, Staphylococcus aureus enterotoxin B (SEB, 1 microg/ml), thus preventing disruption of the epithelial barrier. Pretreatment or co-treatment of human PBMC or murine lymphnode cells with EGCG significantly reduced SEB-induced proliferation and IL-2, IFNgamma, and TNFalpha production. ConA-induced proliferation was also inhibited by EGCG (50 microM) co-treatment. These effects of EGCG were not due to induction of immune cell apoptosis, and were independent of EGCGs anti-oxidant activity, and inhibition of NF-kappaB or AP-1 activation. Moreover, addition of exogenous IL-2 (20 ng/ml) to the cultures could not overcome the immunosuppressive effect of EGCG. Culture supernatant from PBMC stimulated in the presence of EGCG failed to increase the permeability of T84 epithelial cell monolayers: a finding consistent with the reduced IFNgamma and TNFalpha production by SAg+EGCG treated PBMC. These data promote EGCG as a suppressor of T cell activation, and given the prominent role that bacteria and T cells play in inflammatory disease we suggest that EGCG could be a useful addition to current treatments for enteric immune disorders and T cell driven immunopathologies.

 

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CIS

Clinical Immunology Society

The official journal of CIS

http://129.35.76.177/wps/find/journaldescription.cws_home/622806/description#description

 

Volume 110, Issue 1, Pages 100-108 (January 2004)

 

Bayer J, Gomer A, Demir Y, Amano H, Kish DD, Fairchild R, Heeger PS.

Effects of green tea polyphenols on murine transplant-reactive T cell immunity.

The Transplantation Research Program, The Department of Immunology and The Glickman Urologic Institute, The Cleveland Clinic Foundation, Cleveland, Ohio, USA.

Green tea polyphenols (GrTP), the active ingredient of green tea, may have immunosuppressive properties, but whether and how GrTP affect transplant-reactive T cells is unknown. To address this, we tested the effects of GrTP on in vitro and in vivo transplant-reactive T cell immunity. GrTP inhibited IFNgamma secretion by cultured monoclonal T cells and by alloreactive T cells in mixed lymphocyte reactions. Oral GrTP significantly prolonged minor antigen-disparate skin graft survival and decreased the frequency of donor-reactive interferon gamma-producing T cells in recipient secondary lymphoid organs compared to controls. In contrast to other hypothesized actions, oral GrTP did not alter dendritic cell trafficking to lymph nodes or affect metalloproteinase activity in the graft. This is the first report of an immunosuppressive effect of GrTP on transplant-reactive T cell immunity. The results suggest that oral intake of green tea could act as an adjunctive therapy for prevention of transplant rejection in humans.

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http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14962801&dopt=Abstract