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

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 μmol/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.

Key words: EGCG, HIV, p24, subtypes, lymphocytes, alternative therapy, green tea, apoptosis, cytotoxicity, proliferation

Abbreviations used: CC₅₀, 50% Cytotoxicity concentration, ECG, Epicatechin gallate, EGCG, Epigallocatechin gallate, gp120, Glycoprotein 120, IC₅₀, 50% Inhibitory concentration, PI, Propidium iodide