Ferroptosis plays an essential role in the antimalarial mechanism of low-dose dihydroartemisinin.

The activation of artemisinin and its derivatives (ARTs) to generate ROS and other free radicals is mainly heme- or ferrous iron-dependent. ARTs induce ferroptosis in tumor cells, although the involvement of ferroptosis in malaria remains unclear. We found that three typical inducers of ferroptosis (erastin, RSL3 and sorafenib) could effectively mimic DHA inhibition on the growth of blood-stage parasites, which exhibited synergistic or nearly additive interactions in vitro with DHA, while the combination of DHA with ferroptosis inhibitors (deferoxamine, liproxstatin-1) had an obvious antagonistic effect.

[Reasearch on lipid metabolism of Plasmodium and antimalarial mechanism of artemisinin].

As a unicellular organism, Plasmodium displays a panoply of lipid metabolism pathways that are seldom found together in a unicellular organism. These pathways mostly involve the Plasmodium-encoded enzymatic machinery and meet the requirements of membrane synthesis during the rapid cell growth and division throughout the life cycle. Different lipids have varied synthesis and meta-bolism pathways.

[Research progress on energy metabolism of Plasmodium at erythrocytic stage].

As a single-cell organism, Plasmodium has a large and complex metabolic network system. There is a close relationship between various metabolic pathways to maintain the transformation of Plasmodium's own energy and substances. Plasmodium energy metabolism pathways mainly include glycolysis and oxidative phosphorylation.

[Research progress of effect of artemisinin family drugs on T lymphocytes immunomodulation].

Artemisinin was isolated from traditional Chinese herb Artemisia annua for treating malaria. A series of derivatives,like dihydroartemisinin,artesunate,artemether,artether,had the same core chemical structure,and sesquiterpene lactone containing peroxide bridge constitute the basic chemical structure. Besides anti-malaria,artemisinin family drugs were found to ameliorate many different diseases,which have attracted wide attention in recent years.

Effect of Dihydroartemisinin on NADH-Dependent Glutamate Synthase: The Implication in Malaria Management.

Artemisinin and its analogues (ARTs) are currently the most effective anti-malarial drugs, but the precise mechanism of action is still highly controversial. Effects of ARTs on genes expression are studied in our Lab. The overexpression of an interesting amidotransferase, NADH-dependent glutamate synthase (NADH-GltS) was found in treated by dihydroartemisinin (DHA).

[Ferroptosis pathway and its intervention regulated by Chinese materia medica].

Ferroptosis is a new form of regulated cell death which is different from apoptosis, necrosis and autophagy, and results from iron-dependent lipidperoxide accumulation. Now, it is found that ferroptosis is involved in multiple physiological and pathological processes, such as cancer, arteriosclerosis, neurodegenerative diseases, diabetes, antiviral immune response, acute renal failure, hepatic and heart ischemia/reperfusion injury. On the one hand, it could be found the appropriate drugs to promote ferroptosis to clear cancer cells and virus infected cells, etc.

[Research progress on heme metabolism in intraerythrocytic plasmodium].

Heme is a key metabolic factor in all life. Malaria parasite has de novo heme-biosynthetic pathway, however the growth and development of parasite depend on the hemoglobin-derived heme metabolism process during the intraerythrocytic stages, such as the ingestion and degradation of hemoglobin in the food vacuole. The hemoglobin metabolism in the food vesicles mainly includes four aspects: hemoglobin transport and intake, hemoglobin enzymolysis to produce heme, heme polymerization into malarial pigment, and heme transport via the food vacuole.

[Effect of dihydroartemisinin on permeability of human erythrocyte membrane infected plasmodium].

In view of the fact that the antimalarial effects of artemisinins are significant but the mechanism has not yet been clarified and there are many different opinions, it is possible that artemisinins can produce high anti-malarial efficacy through various mechanisms and multiple pathways. In addition, the researches on the pathogenesis of malaria "erythrocyte membrane plasmodial surface anion channel (PSAC)" in the past few years have provided more positive findings, which may confirm and discover the new antimalarial mechanism of artemisinins. This paper was as to study the effect of dihydroartemisinin (DHA) in vitro on erythrocyte membrane permeability of HB3 plasmodium infection, with using the mechanism of 5% sorbitol can be used to kill the Plasmodium falciparum in red blood cell membrane selectively, the effectual difference of sorbitol on the killing of P.

[Effect of dihydroartemisinin at low concentration on intervention of Plasmodium falciparum 3D7 strain].

Malaria is still the most severe strain of the human malaria parasites, and malaria disease is life-threatening which can result in severe anemia and cerebral malaria, especially in children in tropical Africa. Previous studies have shown that artemisinin and its derivatives could selectively kill erythrocytic stage of malaria and have a greater impact on the ring period. In recent years, there have been new findings of its mechanism continually.

[Protective effects of artesunate combination on experimental cerebral malaria and nerve injury].

Cerebral malaria (CM) is the leading cause of death in children under 5 years in Africa, severe neurological sequelae may occur in surviving children. Although artesunate has made breakthrough progress in the clinical treatment of CM, the clinical problems of high mortality and high morbidity have not yet been completely resolved. In this study, an experimental cerebral malaria (ECM) model was established by infecting C57BL/6 mice with Pb ANKA (Plasmodium berghei ANKA) to compare parasitemia level, survival rates, and rapid murine coma behavior scale scores, cerebral microvascular obstruction, haemozoin deposition in the liver, body temperature and weight to investigate the anti-cerebral malaria effect of the artesunate compound combination.