Preclinical development of the green tea catechin, epigallocatechin gallate, as an HIV-1 therapy - PubMed (original) (raw)

Preclinical development of the green tea catechin, epigallocatechin gallate, as an HIV-1 therapy

Christina L Nance et al. J Allergy Clin Immunol. 2009 Feb.

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.

Conclusion: 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.

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Figures

FIG 1

FIG 1

EGCG-induced inhibition of HIV-1 infectivity. HIV-1 p24 antigen production in freshly isolated human CD4+ T cells (●) and macrophages (▲) was measured by ELISA with subtype B, R5-HIV-1Ba-L for 7 days in the presence of EGCG, medium, control catechin, (−)-catechin, or ritonavir. The data are expressed as means ±SD of three separate experiments.

FIG 2

FIG 2

Effect of catechins on HIV-1 p24 antigen production in human lymphocytes. HIV-1 p24 antigen production was measured in the presence and absence of the green tea catechins, (−)-catechin, ECG, EGC, and EGCG at 50μM and the black tea catechin, theaflavin at 20μM. The data are expressed as means ±SD of three separate experiments.

FIG 3

FIG 3

EGCG inhibition of HIV-1 p24 antigen production in human macrophages using different HIV-1 subtypes; A) subtype B, R5-HIV-1SF162, B) subtype B, R5/X4-HIV-189.6, C) subtype D, X4-HIV-192UG038 and D) subtype G, R5-HIV-1JV1083. The data are expressed as means ±SD of three experiments for A) and B); of two experiments for C) and D)..

FIG 4

FIG 4

Effect of EGCG on apoptosis of human lymphocytes. Flow cytometric determination of apoptosis on PBMC after 24 hours in the presence or absence of EGCG. A) Representative histogram of Annexin-V (x-axis) and PI (y-axis) staining. Percent Annexin +/PI− are indicated in quadrant 4. B) Graphic representation of histogram data in A compared to baseline. A) representative of two experiments and B) expressed as means ±SD.

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