Department of Pharmacology, Faculty of Science, Mahidol University, Bangkok 10400, Thailand.
Biol Pharm Bull. 2012;35(1):29-33. doi: 10.1248/bpb.35.29.
Artemisinin exerts the antimalarial activity through activation by heme. The hemolysis in malaria results in the elevated levels of plasma heme which may affect the activity of artemisinin. We hypothesized that the extracellular heme would potentiate the antimalarial activity of artemisinin. Hemin (ferric heme) at the pathologic concentrations enhanced the activity of artemisinin against Plasmodium falciparum in vitro and increased the levels of the lipid peroxidation products in the presence of artemisinin. The antimalarial activity of artemisinin and potentiation by hemin was decreased by vitamin E. Hemin had no effect on the activity of quinoline drugs (chloroquine, quinine and mefloquine). Furthermore, the oxidative effect of hemin in the presence of artemisinin or quinoline drugs was studied using low-density lipoprotein (LDL) oxidation as a model. Artemisinin enhanced the effects of hemin on lipid peroxidation and a decrease of tryptophan fluorescence in LDL whereas the quinoline drugs inhibited the oxidation by hemin. In conclusion, the extracellular hemin enhances the antimalarial activity of artemisinin as a result of the increasing oxidative effect of hemin.
青蒿素通过血红素激活发挥抗疟作用。疟疾导致的溶血会使血浆血红素水平升高，这可能会影响青蒿素的活性。我们假设细胞外血红素可以增强青蒿素的抗疟活性。病理浓度的血红素（三价血红素）增强了青蒿素在体外对抗恶性疟原虫的活性，并在青蒿素存在的情况下增加了脂质过氧化产物的水平。维生素 E 降低了青蒿素和血红素的增效作用。血红素对喹啉类药物（氯喹、奎宁和甲氟喹）无作用。此外，还使用低密度脂蛋白（LDL）氧化作为模型研究了血红素在青蒿素或喹啉类药物存在下的氧化作用。青蒿素增强了血红素对脂质过氧化的作用，并降低了 LDL 中色氨酸的荧光，而喹啉类药物抑制了血红素的氧化作用。总之，细胞外血红素通过增加血红素的氧化作用来增强青蒿素的抗疟活性。
