Milagre Matheus Marques, Torchelsen Fernanda Karoline Vieira da Silva, Pedrosa Tamiles Caroline Fernandes, Teixeira Gabriel Marques, Sampaio Larissa Silva, Saúde-Guimarães Dênia Antunes, Branquinho Renata Tupinambá, Mosqueira Vanessa Carla Furtado, Lana Marta de
Universidade Federal de Ouro Preto, Escola de Farmácia, Programa de Pós-Graduação em Ciências Farmacêuticas, Ouro Preto, Minas Gerais, 35400-000, Brazil.
Universidade Federal de Ouro Preto, Instituto de Ciências Exatas e Biológicas, Programa de Pós-Graduação em Ciências Biológicas, Brazil.
Exp Parasitol. 2023 Dec;255:108647. doi: 10.1016/j.exppara.2023.108647. Epub 2023 Oct 30.
Chagas disease (CD) remains neglected and causes high morbidity and mortality. The great difficulty is the lack of effective treatment. The current drugs cause side effects and have limited therapeutic efficacy in the chronic phase. This study aims to fulfil some gaps in studies of the natural substance lychnopholide nanoencapsulated LYC-PLA-PEG-NC (LYC-NC) and free (Free-LYC): the activity in epimastigotes and amastigotes to determine its selectivity index (SI), the therapeutic efficacy in mice infected with Colombian Trypanosoma cruzi strain and insight of the mechanism of LYC-NC action on T. cruzi. The SI was obtained by calculation of the ratio between the IC value toward H9c2 cells divided by the IC value in the anti-T. cruzi test. Infected Swiss mice were treated with 2 and 12 mg/kg/day via intravenous and oral, respectively, and the therapeutic efficacy was determined. The IC of LYC-NC and Free-LYC for epimastigotes of T. cruzi were similar. Both were active against amastigotes in cell culture, particularly Free-LYC. The SI of LYC-NC and Free-LYC were 45.38 and 32.11, respectively. LYC-NC 2 and 12 mg/kg/day cured parasitologically, 62.5% and 80% of the animals, respectively, infected with a strain resistant to treatment. The fluorescent NC was distributed in the cardiomyocyte cytoplasm, infected or not, and interacted with the trypomastigotes. Together, these results represent advances in demonstrating LYC as a potent new therapeutic option for treating CD.
恰加斯病（CD）仍然被忽视，并且导致高发病率和死亡率。最大的困难在于缺乏有效的治疗方法。目前的药物会产生副作用，并且在慢性期的治疗效果有限。本研究旨在填补关于天然物质lychnopholide纳米包封的LYC-PLA-PEG-NC（LYC-NC）和游离型（游离LYC）研究中的一些空白：在无鞭毛体和无鞭毛体中的活性以确定其选择性指数（SI），对感染哥伦比亚克氏锥虫菌株的小鼠的治疗效果以及对LYC-NC作用于克氏锥虫机制的深入了解。通过计算对H9c2细胞的IC值与抗克氏锥虫试验中的IC值之比来获得SI。分别通过静脉内和口服给予感染的瑞士小鼠2和12mg/kg/天，并确定治疗效果。LYC-NC和游离LYC对克氏锥虫无鞭毛体的IC相似。两者在细胞培养中均对无鞭毛体有活性，特别是游离LYC。LYC-NC和游离LYC的SI分别为45.38和32.11。LYC-NC 2和12mg/kg/天分别使62.5%和80%感染了耐药菌株的动物在寄生虫学上得到治愈。荧光纳米包封物分布在心肌细胞质中，无论是否被感染，并与锥鞭毛体相互作用。总之，这些结果代表了在证明LYC作为治疗恰加斯病的一种有效的新治疗选择方面取得的进展。
