Hong-Ping Hou1, Guang-Ping Zhang1, Li-Na Ma1, Ping Su1, Zhong-Xiu Zhang1, Bao-Qiang Dai1, Zu-Guang Ye2. 1. Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China. 2. Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China. zgye@icmm.ac.cn.
Abstract
OBJECTIVE: To study the antimalarial effects and mechanisms of artemisinin (Qinghaosu in Chinese, QHS) on mitochondria in mice infected with Plasmodium berghei. METHODS: A total of 108 C57 mice infected with Plasmodium berghei were randomly divided into 3 groups by weight: the control group, 200 and 400 mg/kg QHS groups. The two QHS treatment groups were further divided into 4 sub-groups with 12 animals each time according to the treatment time, 0.5, 1, 2, and 4 h. Normal saline was intragastrically (i.g.) administered to the control group. The other two groups received different doses of QHS by i.g. administration. Animals were treated once with QHS for different detection time as follows: 0.5, 1, 2, and 4 h. The mitochondrial energy metabolism, oxidative damage, membrane potential, and membrane permeability and other indexes were detected. RESULTS: After administration of 200 and 400 mg/kg QHS, adenosine triphosphate (ATP) levels in Plasmodium and its mitochondria were reduced (P<0.05), the levels of reactive oxygen species (ROS) and malondialdehyde (MDA) were increased (P<0.05), and the activity of superoxide dismutase (SOD) was also increased (P<0.05). At the same time, the membrane potential of the mitochondria was reduced and the degree to which the membrane permeability transition pore was opened was irreversibly increased (P<0.05). CONCLUSIONS: Mitochondria in Plasmodium were the targets of QHS, which can adversely affect mitochondrial energy metabolism, oxidative damage, membrane potential, and membrane opening, and ultimately exert an antimalarial effect.
OBJECTIVE: To study the antimalarial effects and mechanisms of artemisinin (Qinghaosu in Chinese, QHS) on mitochondria in miceinfected with Plasmodium berghei. METHODS: A total of 108 C57 miceinfected with Plasmodium berghei were randomly divided into 3 groups by weight: the control group, 200 and 400 mg/kg QHS groups. The two QHS treatment groups were further divided into 4 sub-groups with 12 animals each time according to the treatment time, 0.5, 1, 2, and 4 h. Normal saline was intragastrically (i.g.) administered to the control group. The other two groups received different doses of QHS by i.g. administration. Animals were treated once with QHS for different detection time as follows: 0.5, 1, 2, and 4 h. The mitochondrial energy metabolism, oxidative damage, membrane potential, and membrane permeability and other indexes were detected. RESULTS: After administration of 200 and 400 mg/kg QHS, adenosine triphosphate (ATP) levels in Plasmodium and its mitochondria were reduced (P<0.05), the levels of reactive oxygen species (ROS) and malondialdehyde (MDA) were increased (P<0.05), and the activity of superoxide dismutase (SOD) was also increased (P<0.05). At the same time, the membrane potential of the mitochondria was reduced and the degree to which the membrane permeability transition pore was opened was irreversibly increased (P<0.05). CONCLUSIONS: Mitochondria in Plasmodium were the targets of QHS, which can adversely affect mitochondrial energy metabolism, oxidative damage, membrane potential, and membrane opening, and ultimately exert an antimalarial effect.
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