Zhang Jili, Si Hongfei, Li Bing, Zhou Xuzheng, Zhang Jiyu
Key Laboratory of Veterinary Pharmaceutical Development, Ministry of Agriculture, Lanzhou, China.
Key Laboratory of New Animal Drug Project of Gansu Province, Lanzhou, China.
Front Microbiol. 2019 Sep 18;10:2152. doi: 10.3389/fmicb.2019.02152. eCollection 2019.
is a widespread obligatory parasitic protozoon that infects nearly all warm-blooded animals and causes toxoplasmosis. However, the current treatments for toxoplasmosis are limited by severe side effects. Myrislignan is a natural product from Houtt with wide pharmacological activities. In the current study, we tested the anti- activity of myrislignan both and and explored its potential mechanism of action. The cytotoxicity of myrislignan in African green monkey kidney (Vero) cells was assessed using Cell Counting Kit-8 (CCK-8) assays. The effects of myrislignan on were determined by quantitative PCR and Giemsa staining. An murine model of infection was used to determine the efficacy of myrislignan. The changes in tachyzoites after myrislignan exposure were examined by electron microscopy. The impact of myrislignan on mitochondrial function in tachyzoites was assessed by MitoTracker Red CMXRos staining and an ATP detection kit. , myrislignan inhibited tachyzoite proliferation with a 50% effective concentration of 32.41 μg/ml, and reduced the invasion of cells by tachyzoites (14.63 and 1.92% invasion rates for control and 70 μg/ml myrislignan, respectively). Importantly, myrislignan had no significant cytotoxicity against Vero cells at concentrations less than 132 μg/ml. In addition, surface shrinkage and mitochondrial damage were observed in tachyzoites after myrislignan exposure. The reduced Δ and ATP levels in tachyzoites treated with myrislignan further confirmed mitochondrial damage. In the murine model, myrislignan treatment significantly reduced the parasite burden in tissues compared to no treatment. In conclusion, myrislignan had potent anti- activities both and and these activities might involve the interruption of mitochondrial function. These data suggest that myrislignan might be a useful compound for the treatment of toxoplasmosis.
是一种广泛存在的 obligatory 寄生原生动物,可感染几乎所有温血动物并引起弓形虫病。然而,目前治疗弓形虫病的方法受到严重副作用的限制。肉豆蔻木脂素是一种从胡桐属植物中提取的天然产物,具有广泛的药理活性。在本研究中,我们测试了肉豆蔻木脂素对 和 的抗活性,并探讨了其潜在的作用机制。使用细胞计数试剂盒 -8(CCK -8)测定法评估肉豆蔻木脂素在非洲绿猴肾(Vero)细胞中的细胞毒性。通过定量 PCR 和吉姆萨染色确定肉豆蔻木脂素对 的影响。使用 感染的 小鼠模型来确定肉豆蔻木脂素的疗效。通过电子显微镜检查肉豆蔻木脂素暴露后速殖子的变化。通过 MitoTracker Red CMXRos 染色和 ATP 检测试剂盒评估肉豆蔻木脂素对速殖子线粒体功能的影响。 ,肉豆蔻木脂素抑制 速殖子增殖,50%有效浓度为 32.41 μg/ml,并降低速殖子对细胞的侵袭(对照组和 70 μg/ml 肉豆蔻木脂素的侵袭率分别为 14.63%和 1.92%)。重要的是,肉豆蔻木脂素在浓度低于 132 μg/ml 时对 Vero 细胞没有明显的细胞毒性。此外,肉豆蔻木脂素暴露后在速殖子中观察到表面收缩和线粒体损伤。用肉豆蔻木脂素处理的速殖子中 Δ 和 ATP 水平降低进一步证实了线粒体损伤。在 小鼠模型中,与未治疗相比,肉豆蔻木脂素治疗显著降低了组织中的寄生虫负荷。总之,肉豆蔻木脂素在 和 方面均具有强大的抗 活性,这些活性可能涉及线粒体功能的中断。这些数据表明肉豆蔻木脂素可能是一种治疗弓形虫病的有用化合物。
(注:原文中部分“ obligatory ”“ ”“ ”等表述可能存在信息缺失或错误,导致译文部分语句不太通顺,但按照要求忠实翻译。)