Last Updated: 17/09/2024
Study on the antimalarial mechanism of artemisinins based on red blood cell membrane Plasmodium-induced anion channels (PSAC)
Objectives
*The title and abstract were machine translated from Mandarin
The study propose to identify the mechanisms of antimalarial action that allow artemisinins to exert its dual benefit through plasmodial surface anion channel (PSAC), further to illuminate the relationship between PSAC channel activity and the main ion channel activity of erythrocyte membrane, to provide a mechanistic overview of the action of artemisinins.
Artemisinin, discovered by Chinese scientists in the early 1970s, is an effective antimalarial drug with low toxicity. Although intensive efforts have been devoted to explore the mode of action of this class of drugs, its exact mechanism remains an enigma. Many hypotheses have been proposed, such as iron and heme model, mitochondria model, PfATP6 model, and so forth. Recent studies have demonstrated that malaria infected erythrocytes show increased permeability to a number of ions and various nutrient solutes important for parasite growth as mediated by the Plasmodial Surface Anion Channel (PSAC). The hypothesis is that antimalarial action of artemisinins on parasite growth and proliferation is performed through inhibiting clag3-induced PSAC activity. Previous study showed that Dihydroartemisinin (DHA) possess potent inhibitory activities on parasite viability: Here, to investigate the effects of artemisinins on the main ion channel, PSAC channel activity and the P. falciparum clag3 gene of iRBC membrane, this project applied the relevant experimental techniques such as whole-cell patch-clamp configuration and gene silencing and switched etc. The hope is that these findings provide a useful starting point for deciphering mechanisms of antimalarial action of artemisinins in the malaria infected erythrocyte.
Jan 2019 — Dec 2021
$31,116
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