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

GUO Yuan1 LI Kai2,3 JIANG Xiao-hui2,3 YANG Ting1,2 ZHENG Zhong-yuan1,2 CHEN Li-na2,3 LI Yu-jie2,3 ZHENG Xiao-jun4

(1.College of Pharmacy, Shanxi Medical University, Taiyuan, China 030001)
(2.Research Center of Artemisinin, China Academy of Chinese Medical Sciences, Beijing, China 100700)
(3.Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China 100700)
(4.Pharmacy Department, First Hospital of Shanxi Medical University, Taiyuan, China 030001)

【Abstract】Malaria is an infectious disease affecting humans especially for children in tropical Africa. Previous studies have shown that artemisinin and its derivatives could selectively kill erythrocytic stage of malaria parasite and have a greater impact on the ring stage. In recent years, there have been new findings of its mechanism. However, the concentrations of artemisinin and its derivatives used in these studies can reach 50 to 80 times the half-inhibitory concentration in vitro. In this study, the international standard strain 3D7 of Plasmodium falciparum was cultured in vitro. After the strain was treated with half-inhibitory concentration of dihydroartemisinin (DHA), the morphological changes of intraerythrocytic P. falciparum were observed, and then the 3D7 life cycle and effects of DHA on this strain at different developmental stages were explored. The 3D7 strain of P. falciparum was continuously synchronised for more than three times, and DHA at half maximal inhibitory concentration (10 nmol·L−1) was administered for 6 h after the last synchronization, and three life cycles were continuously observed (132 h). The results showed that compared with the parasites untreated by DHA, there was a noticeable delay in the life cycle of at least 36 h, indicating that the growth of 3D7 was significantly inhibited by DHA (P < 0.001), and the rate of ring formation was significantly reduced (P < 0.05). The trophozoites were abnormal in shape, such as shrink in size, and the number of merozoites in schizonts was significantly decreased (P < 0.05). These results suggest that non-killing (meaning parasites can be inhibited but not killed) concentration of DHA can significantly inhibit the growth of P. falciparum, which may not only affect the ring stage, but also have an impact on other stages of P. falciparum.

【Keywords】 dihydroartemisinin; Plasmodium falciparum; erythrocytic stage of malaria; life cycle;

【Funds】 National Natural Science Foundation of China (81641002) Key Project of China Academy of Chinese Medical Sciences during the 13th Five-Year Plan of China (Z2017021) National Major Scientific and Technological Special Project for “Significant New Drugs Development” (2017ZX09101002)

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This Article

ISSN:1001-5302

CN: 11-2272/R

Vol 43, No. 16, Pages 3397-3403

August 2018

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Article Outline

Abstract

  • 1 Materials
  • 2 Methods
  • 3 Results
  • 4 Discussion
  • References