Plasmodium yoelii

Publication Title: 
The American Journal of Clinical Nutrition

Young female mice were fed torula-yeast-based diets deficient in vitamin E or selenium or supplemented with cod-liver oil to determine the effect of host antioxidant status on the therapeutic efficacy of the Chinese traditional antimalarial drug qinghaosu (QHS), a sesquiterpene endoperoxide. Vitamin E deficiency enhanced the antimalarial action of QHS against Plasmodium yoelii, both in terms of decreased parasitemia and improved survival but Se deficiency did not.

Author(s): 
Levander, O. A.
Ager, A. L.
Morris, V. C.
May, R. G.
Publication Title: 
Zhongguo Yao Li Xue Bao = Acta Pharmacologica Sinica

The effects of alpha-dimethylamino-cyclohexoxyl-dimethyl gallium (DCDG), a new antimalarial drug developed in China, on the ultrastructure of murine malaria parasites in vivo was studied in comparison with those of chloroquine (CQ) and artemisinin (Art). All these 3 antimalarials were administered ig to mice at dosages of 1-3, 40-80, and 200-400 mg.kg-1 for DCDG, CQ, and Art respectively, based on a similar intensity of morphological changes in the parasites. Blood samples were collected for electron microscopy from 15 min to 48 h after medication.

Author(s): 
Yan, G. H.
Wang, G. J.
Li, Y. C.
Publication Title: 
Tropical medicine & international health: TM & IH

Glutathione-S-transferase (GST) activity has been detected in rodent (Plasmodium berghei, P. yoelii), simian (P. knowlesi) and human (P. falciparum) malarial parasites, and in different intraerythrocytic stages of P. knowlesi (schizont > ring > trophozoite). In chloroquine-resistant strains of rodent and human malarial parasites GST activity significantly increases compared to sensitive strains. Further, the increase in enzyme activity is directly related to drug pressure of resistant P. berghei. Complete inhibition of chloroquine-sensitive and resistant P.

Author(s): 
Srivastava, P.
Puri, S. K.
Kamboj, K. K.
Pandey, V. C.
Publication Title: 
The Journal of Biological Chemistry

Endoperoxide antimalarials based on the ancient Chinese drug Qinghaosu (artemisinin) are currently our major hope in the fight against drug-resistant malaria. Rational drug design based on artemisinin and its analogues is slow as the mechanism of action of these antimalarials is not clear. Here we report that these drugs, at least in part, exert their effect by interfering with the plasmodial hemoglobin catabolic pathway and inhibition of heme polymerization. In an in vitro experiment we observed inhibition of digestive vacuole proteolytic activity of malarial parasite by artemisinin.

Author(s): 
Pandey, A. V.
Tekwani, B. L.
Singh, R. L.
Chauhan, V. S.
Publication Title: 
Antimicrobial Agents and Chemotherapy

Artemisinin and its derivatives are important new antimalarials which are now used widely in Southeast Asia. Clinically relevant artemisinin resistance has not yet been reported but is likely to occur. In order to understand how the malaria parasite might become resistant to this drug, we studied artemisinin resistance in the murine malaria parasite Plasmodium yoelii. The artemisinin-resistant strain (ART), which is approximately fourfold less sensitive to artemisinin than the sensitive NS strain, accumulated 43% less radiolabeled drug in vitro (P < 0.01).

Author(s): 
Walker, D. J.
Pitsch, J. L.
Peng, M. M.
Robinson, B. L.
Peters, W.
Bhisutthibhan, J.
Meshnick, S. R.
Publication Title: 
Chemistry & Biology

A lack of molecular understanding of the targets and mechanisms of artemisinin action has impeded the improvisation of more efficient antimalarials based on this class of endoperoxide drugs. We have synthesized a heme-artemisinin adduct designated as "hemart" to discover if it mediates the ability of artemisinin to inhibit heme polymerization. Hemart mimics heme in binding to Plasmodium falciparum histidine-rich protein II (PfHRP II) but cannot self-polymerize.

Author(s): 
Kannan, R.
Sahal, Dinkar
Chauhan, V. S.
Publication Title: 
Tropical Biomedicine

Eurycoma longifolia, locally known as 'Tongkat Ali' is a popular local medicinal plant that possess a lot of medicinal properties as claimed traditionally, especially in the treatment of malaria. The claims have been proven scientifically on isolated compounds from the plant. The present study is to investigate the anti malaria properties of Eurycoma longifolia standardized extract (root) (TA164) alone and in combination with artemisinin in vivo. Combination treatment of the standardized extract (TA164) with artemisinin suppressed P. yoelii infection in the experimental mice.

Author(s): 
Mohd Ridzuan, M. a. R.
Sow, A.
Noor Rain, A.
Mohd Ilham, A.
Zakiah, I.
Publication Title: 
FASEB journal: official publication of the Federation of American Societies for Experimental Biology

Malarial parasites have evolved resistance to all previously used therapies, and recent evidence suggests emerging resistance to the first-line artemisinins. To identify antimalarials with novel mechanisms of action, we have developed a high-throughput screen targeting the apicoplast organelle of Plasmodium falciparum. Antibiotics known to interfere with this organelle, such as azithromycin, exhibit an unusual phenotype whereby the progeny of drug-treated parasites die.

Author(s): 
Ekland, Eric H.
Schneider, Jessica
Fidock, David A.
Publication Title: 
PloS One

Plasmodium falciparum malaria is a major global health problem, causing approximately 780,000 deaths each year. In response to the spreading of P. falciparum drug resistance, WHO recommended in 2001 to use artemisinin derivatives in combination with a partner drug (called ACT) as first-line treatment for uncomplicated falciparum malaria, and most malaria-endemic countries have since changed their treatment policies accordingly. Currently, ACT are often the last treatments that can effectively and rapidly cure P.

Author(s): 
Witkowski, Benoit
Lelièvre, Joel
Nicolau-Travers, Marie-Laure
Iriart, Xavier
Njomnang Soh, Patrice
Bousejra-Elgarah, Fatima
Meunier, Bernard
Berry, Antoine
Benoit-Vical, Françoise
Publication Title: 
Antimicrobial Agents and Chemotherapy

Evidence of artemisinin (ART) resistance in all of the Greater Mekong Region is currently of major concern. Understanding of the mechanisms of resistance developed by Plasmodium against artemisinin and its derivatives is urgently needed. We here demonstrated that ART was able to alkylate heme in mice infected by the ART-susceptible strain of Plasmodium yoelii nigeriensis, Y-control. After long-term drug pressure, the parasite strain (Y-ART3) was 5-fold less susceptible to ART than Y-control. In the blood of mice infected by Y-ART3, no heme-artemisinin adducts could be detected.

Author(s): 
Robert, Anne
Claparols, Catherine
Witkowski, Benoit
Benoit-Vical, Françoise

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