Broad inhibition of plasmodium falciparum cytoadherence by (+)-epigallocatechin gallate
Broad inhibition of plasmodium falciparum cytoadherence by (+)-epigallocatechin gallate
复制标题
( )-表没食子儿茶素没食子酸酯广泛抑制恶性疟原虫细胞粘附
作者：
Pradeep R. Patil;S. Gemma;G. Campiani;A. Craig
背景恶性疟原虫表面抗原EMP-1是恶性疟原虫的一个重要毒力因子，参与恶性疟原虫感染红细胞与宿主内皮细胞上一系列受体的粘附。在这些宿主受体中，与ICAM-1的结合与脑型疟疾有关。尽管使用了有效的抗寄生虫药物，但大多数脑型疟疾患儿的死亡率在入院后24 h内出现，因此，迫切需要开发抗寄生虫药物，多酚化合物（+）-表没食子儿茶素没食子酸酯（（+）-EGCG）先前已使用少量实验室寄生虫分离株评估了其抗粘附特性。在此，使用一组新的ICAM-1结合恶性疟原虫患者分离株进一步探索该特性，以确定（+）-EGCG是否可能有效地作为基于ICAM-1的细胞粘附的广谱抑制剂。在存在和不存在50 μM（+）-EGCG的静态测定条件下，使其与ICAM-1-Fc蛋白结合。结果（+）-EGCG能显著降低患者分离株与人ICAM-1的结合，抑制率为37%（P <0.05）。（+）-EGCG能显著降低患者分离株与人ICAM-1的结合，抑制率为37%（P <0.05）。在50 μM（+）-EGCG时，在患者分离株BC-12中最高达80%，在患者分离株8146中最高达80%。结论（+）-EGCG对一组新的ICAM-1结合患者恶性疟原虫分离株的抗粘附特性的评价表明，这种被鉴定为人ICAM-1的L43环的潜在模拟物的抑制剂，能有效阻断细胞粘附。
BackgroundThe surface antigen Pf EMP-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.MethodsPlasmodium 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.ResultsThis 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.ConclusionEvaluation 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.