Broad inhibition of plasmodium falciparum cytoadherence by (+)-epigallocatechin gallate
1 European Research Centre for Drug Discovery and Development, Department of Pharmaceutical and Applied Chemistry, University of Siena, via Aldo Moro 2, Siena 53100, Italy
2 Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK
3 Université Montpellier II Sciences et Techniques, Montpellier, France
Malaria Journal 2011, 10:348 doi:10.1186/1475-2875-10-348Published: 1 December 2011
The surface antigen PfEMP-1 is a key virulence factor of the human malaria parasite implicated in the cytoadherence of Plasmodium falciparum infected erythrocytes to a range of receptors on host endothelium. Among these host receptors, binding to ICAM-1 is related to cerebral malaria. The majority of the mortality in children with cerebral malaria is seen within 24 h of hospital admission despite the use of effective anti-parasite drugs, therefore, the development of adjunctive therapies is urgently needed.
The polyphenolic compound (+)-epigallocatechin gallate ((+)-EGCG) has been previously evaluated for anti-adhesive properties using a small number of laboratory parasite isolates. Here, this property is further explored using a new panel of ICAM-1-binding patient isolates of P. falciparum to ascertain if (+)-EGCG might be effective as a broad spectrum inhibitor of ICAM-1-based cytoadherence.
Plasmodium falciparum lines, including A4 and ItG as positive controls and nine new ICAM-1 binding patient isolates, were allowed to bind with ICAM-1-Fc protein under static assay conditions in the presence and absence of 50 μM (+)-EGCG. Adhesion levels of all the parasite strains were quantified by microscopy as the mean number of infected erythrocyte (IE) bound per mm2 of surface area and statistical comparisons were made to demonstrate the effect of (+)-EGCG on the binding of various parasite variants to human ICAM-1.
This study revealed that binding of patient isolates to ICAM-1 was reduced significantly with inhibition levels of 37% in patient isolate BC-12 up to a maximum of 80% in patient isolate 8146 at 50 μM (+)-EGCG.
Evaluation of the anti-adhesive property of (+)-EGCG against a new panel of ICAM-1-binding patient isolates of P. falciparum showed that this inhibitor, identified as potential mimic of the L43 loop of human ICAM-1, was effective at blocking cytoadherence.