Research Article: Synergistic and Additive Effects of Epigallocatechin Gallate and Digitonin on Plasmodium Sporozoite Survival and Motility

Date Published: January 13, 2010

Publisher: Public Library of Science

Author(s): Janina K. Hellmann, Sylvia Münter, Michael Wink, Friedrich Frischknecht, Laurent Rénia.

Abstract: Most medicinal plants contain a mixture of bioactive compounds, including chemicals that interact with intracellular targets and others that can act as adjuvants to facilitate absorption of polar agents across cellular membranes. However, little is known about synergistic effects between such potential drug candidates and adjuvants. To probe for such effects, we tested the green tea compound epigallocatechin gallate (EGCG) and the membrane permeabilising digitonin on Plasmodium sporozoite motility and viability.

Partial Text: Plant-derived bioactive compounds are attractive candidates for drug development since they represent lead structures for new or existing drug targets. Currently, most medications including antibiotics, anticancer drugs and drugs directed against parasites are based on natural compounds [1], [2], [3]. The active substances in plants are mostly secondary metabolites, which are used as defense compounds against predators or parasites, for interspecies competition or as signal compounds to attract insects or other animals [4]. Plants usually produce and store complex mixtures of compounds from different structural classes to simultaneously interfere with several targets, which is thought to amplify their efficiency and reduce the risk of resistance development by pathogens [5]. While many classes of secondary metabolites interfere with specific molecular targets members of one major secondary metabolite class called polyphenols interact non-selectively like “protein glue” affecting any protein they encounter [1], [2]. Thus, they influence amongst others catalysis, transport, ion exchange or signal transduction pathways of the targeted organism [6], [7].

Here we tested (i) a recently developed assay for its utility in screening for inhibitors of Plasmodium sporozoite motility and (ii) for possible effects of the secondary plant metabolite EGCG together with the saponin digitonin on cytotoxicity and inhibition of motility. This revealed that such a combination of natural compounds results in a more efficient effect on a target cell than application of a single drug as monotherapy. While digitonin showed an additive effect to EGCG on inhibiting motility, it showed a synergistic effect on inhibiting sporozoite survival. However, EGCG inhibited the motility rapidly after 40 minutes, while causing sporozoite death only after several hours.



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