Núcleo de Pesquisa em Doenças Negligenciadas, Universidade Guarulhos, Praça Tereza Cristina, 229, Centro, Guarulhos, SP 07023-070, Brazil.
Departamento de Biologia Animal, Instituto de Biologia, Universidade Estadual de Campinas, Campinas, SP, Brazil.
Int J Antimicrob Agents. 2017 Sep;50(3):467-472. doi: 10.1016/j.ijantimicag.2017.06.005. Epub 2017 Jun 27.
Schistosomiasis is a major public health problem worldwide, especially in poor communities. Since praziquantel is currently the only drug available to treat schistosomiasis, there is an urgent need to identify new antischistosomal drugs. Nerolidol is a sesquiterpene present as an essential oil in several plants that has been approved by the FDA. This study evaluated the in vivo antischistosomal activity of nerolidol in a mouse model of schistosomiasis infected with either adult or juvenile stages of Schistosoma mansoni. A single dose of nerolidol (100, 200 or 400 mg/kg) administered orally to mice infected with adult schistosomes resulted in a reduction in worm burden and egg production. Treatment with the highest nerolidol dose (400 mg/kg) caused significant reduction in a total worm burden of 70.06% (P < 0.001). Additionally, the technique of quantitative and qualitative oograms showed that a single 400 mg/kg nerolidol dose achieved an immature egg reduction of 84.6% (P < 0.001). In faecal samples, the Kato-Katz method also revealed a reduction of 75.2% in eggs/g at a dose of 400 mg/kg (P < 0.001). Furthermore, scanning electron microscopy revealed that nerolidol-mediated worm killing was associated with tegumental damage. In contrast to activity against adult S. mansoni infection, oral treatment with nerolidol 400 mg/kg had low efficacy in mice harbouring juvenile schistosomes. Since nerolidol is already in use globally as a food additive and has a proven safety record, evaluation of this natural compound's potential for treatment of schistosomiasis could be entirely cost effective in the near future.
血吸虫病是全球主要的公共卫生问题,特别是在贫困社区。由于目前只有吡喹酮可用于治疗血吸虫病,因此迫切需要寻找新的抗血吸虫药物。橙花叔醇是一种倍半萜烯,存在于几种植物的精油中,已被 FDA 批准使用。本研究评估了橙花叔醇在感染曼氏血吸虫成虫或幼虫的小鼠血吸虫病模型中的体内抗血吸虫活性。单次口服给予感染成虫的小鼠 100、200 或 400mg/kg 橙花叔醇可降低虫体负荷和产卵量。最高剂量(400mg/kg)的橙花叔醇处理导致总虫体负荷减少 70.06%(P<0.001)。此外,定量和定性卵图技术表明,单次给予 400mg/kg 橙花叔醇可使未成熟卵减少 84.6%(P<0.001)。在粪便样本中,Kato-Katz 法也显示 400mg/kg 剂量可使卵/g 减少 75.2%(P<0.001)。此外,扫描电子显微镜显示,橙花叔醇介导的杀蠕虫作用与表皮损伤有关。与针对成年 S. mansoni 感染的活性相反,口服给予 400mg/kg 橙花叔醇对携带幼虫的小鼠疗效较低。由于橙花叔醇已经作为食品添加剂在全球范围内使用,并且具有已证明的安全性记录,因此评估这种天然化合物治疗血吸虫病的潜力在不久的将来可能具有完全的成本效益。