Fishwick J, McLean W G, Edwards G, Ward S A
Department of Pharmacology and Therapeutics, University of Liverpool, UK.
Chem Biol Interact. 1995 Jun 14;96(3):263-71. doi: 10.1016/0009-2797(94)03597-2.
The antimalarial drug artemisinin and a number of its derivatives were tested for their effects on proliferation of undifferentiated neuroblastoma Nb2a cells and glioma C6 cells in culture as well as their ability to inhibit neurite outgrowth from Nb2a cells differentiated by removal of serum and addition of dibutyryl cyclic AMP. In the Nb2a and C6 cell cultures, all drugs except desoxyartemisinin significantly inhibited cell proliferation in a dose-related manner with the lowest effective concentration being that of artemisinin at 0.1 microM. Artemether, arteether, artemisinin and dihydroartemisinin also produced a dose-related decrease in the number of neurites/extensions formed by differentiating Nb2a cells, with an effect of dihydroartemisinin at a concentration as low as 1 nM. Desoxyartemisinin had no effect on extension/neurite formation. We propose a potential mechanism for neurotoxicity of artemisinin and its derivatives that involves the endoperoxide bridge which is also known to be necessary for their antimalarial action.
对抗疟药物青蒿素及其多种衍生物进行了测试，观察它们对培养中的未分化神经母细胞瘤Nb2a细胞和胶质瘤C6细胞增殖的影响，以及它们抑制血清去除并添加二丁酰环磷腺苷后分化的Nb2a细胞长出神经突的能力。在Nb2a和C6细胞培养物中，除脱氧青蒿素外，所有药物均以剂量相关方式显著抑制细胞增殖，最低有效浓度为青蒿素的0.1微摩尔。蒿甲醚、蒿乙醚、青蒿素和双氢青蒿素还使分化的Nb2a细胞形成的神经突/延伸数量呈剂量相关减少，双氢青蒿素在低至1纳摩尔的浓度时即有作用。脱氧青蒿素对延伸/神经突形成无影响。我们提出了青蒿素及其衍生物神经毒性的一种潜在机制，该机制涉及内过氧化物桥，而这也是其抗疟作用所必需的。
