Golenser Jacob, Waknine Judith H, Krugliak Miriam, Hunt Nicholas H, Grau Georges E
Department of Parasitology - The Kuvin Centre for the Study of Infectious and Tropical Diseases, The Hebrew University of Jerusalem, Jerusalem 91120, Israel.
Int J Parasitol. 2006 Dec;36(14):1427-41. doi: 10.1016/j.ijpara.2006.07.011. Epub 2006 Sep 12.
Artemisinin derivatives are the most recent single drugs approved and introduced for public antimalarial treatment. Although their recommended use is for treatment of Plasmodium falciparum infection, these drugs also act against other parasites, as well as against tumor cells. The mechanisms of action attributed to artemisinin include interference with parasite transport proteins, disruption of parasite mitochondrial function, modulation of host immune function and inhibition of angiogenesis. Artemisinin combination therapies are currently the preferred treatment for malaria. These combinations may prevent the induction of parasite drug resistance. However, in view of the multiple mechanisms involved, especially when additional drugs are used, the combined therapy should be carefully examined for antagonistic effects. It is now a general theory that the crucial mechanism is interference with plasmodial SERCA. Therefore, future development of resistance may be associated with overproduction or mutations of this transporter. However, a general mechanism, such as alterations in general drug transport pathways, is feasible. In this article, we review the evidence for each mechanism of action suggested.
青蒿素衍生物是最近被批准并用于公共抗疟治疗的单一药物。尽管它们的推荐用途是治疗恶性疟原虫感染，但这些药物也对其他寄生虫以及肿瘤细胞有作用。青蒿素的作用机制包括干扰寄生虫转运蛋白、破坏寄生虫线粒体功能、调节宿主免疫功能以及抑制血管生成。青蒿素联合疗法目前是疟疾的首选治疗方法。这些联合疗法可能会防止寄生虫产生耐药性。然而，鉴于涉及多种机制，特别是当使用其他药物时，应仔细检查联合疗法是否存在拮抗作用。现在有一种普遍的理论认为，关键机制是干扰疟原虫的肌浆网钙ATP酶（SERCA）。因此，未来耐药性的发展可能与该转运蛋白的过度产生或突变有关。然而，诸如一般药物转运途径改变等普遍机制也是可行的。在本文中，我们综述了所提出的每种作用机制的证据。
