Planta Med 2006; 72(7): 640-642
DOI: 10.1055/s-2006-931575
Original Paper
Biochemistry and Molecular Biology
© Georg Thieme Verlag KG Stuttgart · New York

Loading of Erythrocyte Membrane with Pentacyclic Triterpenes Inhibits Plasmodium falciparum Invasion

Hanne L. Ziegler1 , Trine Staalsø2 , Jerzy W. Jaroszewski1
  • 1Department of Medicinal Chemistry, The Danish University of Pharmaceutical Sciences, Copenhagen, Denmark
  • 2Centre for Medical Parasitology, Copenhagen University Hospital, Copenhagen, Denmark
Further Information

Publication History

Received: October 8, 2005

Accepted: February 3, 2006

Publication Date:
29 May 2006 (online)

Abstract

Lupeol and betulinic acid inhibit the proliferation of Plasmodium falciparum parasites by inhibition of the invasion of merozoites into erythrocytes. This conclusion is based on experiments employing parasite cultures synchronized by magnetic cell sorting (MACS). Identical inhibitory effects were observed upon incubation of synchronous parasite cultures in the presence of the triterpenoids, and when the parasite cultures were grown in a triterpenoid-free medium with erythrocytes preloaded with the triterpenoids.

References

  • 1 Ziegler H L, Stærk D, Christensen J, Hviid L, Hägerstrand H, Jaroszewski J W. In vitro Plasmodium falciparum drug sensitivity assay: inhibition of parasite growth by incorporation of stomatocytogenic amphiphiles into erythrocyte membrane.  Antimicrob Agents Chemother. 2002;  46 1441-6
  • 2 Sairafianpour M, Bahreininejad B, Witt M, Ziegler H L, Jaroszewski J W, Stærk D. Terpenoids of Salvia hydrangea: Two new, rearranged 20-norabietanes and the effect of oleanolic acid on erythrocyte membranes.  Planta Med. 2003;  69 846-50
  • 3 Ziegler H L, Franzyk H, Sairafianpour M, Tabatabai M, Tehrani M D, Bagherzadeh K. et al . Erythrocyte membrane modifying agents and the inhibition of Plasmodium falciparum growth: structure-activity relationships for betulinic acid analogues.  Bioorg Med Chem. 2004;  12 119-27
  • 4 Paul F, Roath S, Melville D, Warhurst D C, Osisanya J O. Separation of malaria-infected erythrocytes from whole blood: use of a selective high-gradient magnetic separation technique.  Lancet. 1981;  2 70-1
  • 5 Miltenyi S, Müller W, Weichel W, Radbruch A. High gradient magnetic cell separation with MACS.  Cytometry. 1990;  11 231-8
  • 6 Staalsoe T, Giha H A, Dodoo D, Theander T G, Hviid L. Detection of antibodies to variant antigens on Plasmodium falciparum infected erythrocytes by flow cytometry.  Cytometry. 1999;  35 329-36
  • 7 Ziegler H L, Hansen H S, Stærk D, Christensen S B, Hägerstrand H, Jaroszewski J W. The antiparasitic compound licochalcone A is a potent echinocytogenic agent that modifies the erythrocyte membrane in the concentration range where antiplasmodial activity is observed.  Antimicrob Agents Chemother. 2004;  48 4067-71
  • 8 Murphy S C, Samuel B U, Harrison T, Speicher K D, Speicher D W, Reid M E. et al . Erythrocyte detergent-resistant membrane proteins: their characterization and selective uptake during malarial infection.  Blood. 2004;  103 1920-8
  • 9 Parker P D, Tilley L, Klonis N. Plasmodium falciparum induces reorganization of host membrane proteins during intraerythrocytic growth.  Blood. 2004;  103 2404-6
  • 10 Thomas S L, Lew V L. Plasmodium falciparum and the permeation pathway of the host red blood cell.  Trends Parasitol. 2004;  20 122-5
  • 11 Cooke B M, Mohandas N, Coppel R L. Malaria and the red blood cell membrane.  Semin Hematol. 2004;  41 173-88
  • 12 Pei X, An X, Guo X, Tarnawski M, Coppel R, Mohandas N. Structural and functional studies of interaction between Plasmodium falciparum knob-associated histidine-rich protein (KAHRP) and erythrocyte spectrin.  J Biol Chem. 2005;  280 31 166-71
  • 13 Tiffert T, Lew V L, Ginsburg H, Krugalik M, Croisille L, Mohandas N. The hydration state of human red blood cells and their susceptibility to invasion by Plasmodium falciparum .  Blood. 2005;  105 4853-60
  • 14 Nguyen D H, Espinoza J C, Taub D D. Cellular cholesterol enrichment impairs T cell activation and chemotaxis.  Mech Ageing Dev. 2004;  125 641-50
  • 15 Breusegem S Y, Halaihel N, Inoue M, Zajicek H, Lederer E, Barry N P. et al . Acute and chronic changes in cholesterol modulate Na-Pi cotransport activity in OK cells.  Am J Physiol Renal Physiol. 2005;  289 F154-65
  • 16 Brambillasca S, Yabal M, Soffientini P, Stefanovic S, Makarow M, Hedge R S. et al . Transmembrane topogenesis of a tail-anchored protein is modulated by membrane lipid composition.  EMBO J. 2005;  24 2533-42

Prof. Jerzy W. Jaroszewski

Department of Medicinal Chemistry

The Danish University of Pharmaceutical Sciences

Universitetsparken 2

2100 Copenhagen

Denmark

Fax: +45-3530-6040

Email: jj@dfuni.dk