常山酮抗原虫作用研究进展

Research Progress on Antiprotozoal Activity of Halofuginone

寄生虫病是世界上最具破坏性和普遍性的传染病之一,造成每年数万人死亡的同时也导致巨大经济损失。常山酮(halofuginone)是从植物常山中分离提取的活性成分常山碱的卤代衍生物,具有强大的抗原虫活性。与常山碱相比,常山酮毒副作用更小的特点使其在疾病治疗上更有优势。近年来,常山酮在癌症、纤维化和自身免疫性疾病等方面的生物活性引起广泛关注。在人医临床上,常山酮针对杜兴氏肌肉营养不良症、实体瘤等的作用研究已进入临床试验阶段。在兽医临床上,常山酮氢溴酸盐和常山酮乳酸盐已分别被FDA和欧盟授权用于预防和治疗家禽球虫病和反刍动物隐孢子虫病。据报道,常山酮对疟原虫、弓形虫、泰勒虫、利什曼原虫等原虫的感染也有高效的治疗作用。氨酰-tRNA合成酶是寄生虫病治疗的新兴靶点,本文归纳总结了常山酮对多种原虫的作用以及抑制脯氨酰-tRNA合成酶的相关机制,以期为后续常山酮抗原虫的理论研究和临床应用提供参考依据。

Parasitic diseases are the most destructive and pervasive infectious diseases in the world,killing tens of thousands of people annually and causing huge economic losses.Halofuginone is a halogenated derivative of febrifugine isolated and extracted from the plant Changshan,which has strong antiprotozoal activity.Compared with febrifugine,halofuginone has less toxic and side effects,which makes it more advantageous in disease treatment.In recent years,the biological activities of halofuginone in cancer,fibrosis and autoimmune diseases have attracted extensive attention.In human clinical practice,the research on the effects of halofuginone on Duchenne muscular dystrophy and solid tumors has entered the stage of clinical trials.In veterinary clinical practice,halofuginone hydrobromide and halofuginone lactate have been authorized by the FDA and the EU for the prevention and treatment of poultry coccidiosis and ruminant cryptosporidiosis,respectively.Moreover,halofuginone also has efficient inhibition on protozoa parasites such as Plasmodium,Toxoplasma,Theileria,and Leishmania.Aminoacyl-tRNA synthetases are emerging targets for the treatment of parasitic diseases,this review summarizes the effect of halofuginone on various protozoa parasites and the related mechanisms of inhibiting prolyl-tRNA synthetase,and hope to provide a reference for the subsequent theoretical research and clinical application of halofuginone antiprotozoal.