Federal University of Alfenas, Biomedical Sciences Institute, Laboratory of Parasitology, Alfenas, Minas Gerais, Brazil.
Federal University of Alfenas, Department of Clinical and Toxicological Analysis, Alfenas, Minas Gerais, Brazil.
Phytomedicine. 2018 Jan 1;38:66-73. doi: 10.1016/j.phymed.2017.11.001. Epub 2017 Nov 3.
The tetraprenylated benzophenone 7-epiclusianone (7-epi) is a substance isolated from the fruits of Garcinia brasiliensis and in vitro studies have demonstrated that 7-epi is effective against Schistosoma mansoni adult worms.
HYPOTHESIS/PURPOSE: Here we report the in vivo evaluation of 7-epi and its pharmacokinetic in healthy and Schistosoma mansoni infected mice.
In this work, we assayed the schistosomicidal activity of 7-epi at the dose of 100 mg/kg and 300 mg/kg body weight/day in S. mansoni experimentally infected mice. Besides, two groups of animals were treated and a detailed analysis of plasma samples was performed by liquid chromatography coupled to mass spectrometry (LC-MS/MS).
The worm burden showed a reduction in the infected mice after treatment with 300 mg/kg for five days (p < .05). And we found an increase of AUC (20846 vs. 32438 ng.h/ml) and a decrease of total apparent clearance (0.006 vs. 0.004 l/h/kg) of 7- epi in the infected group compared to the healthy group. Consequently, the half-life increased (1.73 vs. 6.11 h) and Cmax was reduced (5427.5 vs. 3321.0 ng/ml) in the infected group compared to the healthy group. In addition, histopathological investigations were performed analysing liver samples from healthy and infected mice.
The results showed significant schistosomicidal in vivo activity at 300 mg/kg. In addition, livers from S. mansoni infected mice showed a greater number of egg granulomas and the changes in the pharmacokinetic parameters in this group could be associated with the pathology of the murine experimental schistosomiasis.
四萜基苯并二氢吡喃酮 7-表衣兰酮（7- epi ）是从巴西胡椒果实中分离得到的一种物质，体外研究表明 7- epi 对曼氏血吸虫成虫有效。
假说/目的：本文报道了 7- epi 的体内评价及其在健康和曼氏血吸虫感染小鼠中的药代动力学。
在这项工作中，我们在曼氏血吸虫实验感染小鼠中检测了 7- epi 在 100mg/kg 和 300mg/kg 体重/天剂量下的杀血吸虫活性。此外，还对两组动物进行了治疗，并通过液相色谱-质谱联用（LC-MS/MS）对血浆样本进行了详细分析。
感染小鼠经 300mg/kg 治疗 5 天后，虫荷减少（p<0.05）。我们发现感染组的 AUC（20846 比 32438ng.h/ml）增加，总表观清除率（0.006 比 0.004 l/h/kg）降低。因此，与健康组相比，感染组的半衰期延长（1.73 比 6.11 h），Cmax 降低（5427.5 比 3321.0 ng/ml）。此外，还对健康和感染小鼠的肝组织进行了组织病理学检查。
结果表明，300mg/kg 时体内具有显著的杀血吸虫活性。此外，感染曼氏血吸虫的小鼠肝脏中出现了更多的虫卵肉芽肿，而该组药代动力学参数的变化可能与实验性血吸虫病的病理学有关。
