Pardo-Rodriguez Daniel, Lasso Paola, Mateus José, Mendez John, Puerta Concepción J, Cuéllar Adriana, Robles Jorge, Cuervo Claudia
Grupo de Enfermedades Infecciosas, Pontificia Universidad Javeriana, Bogotá, Colombia.
Grupo de Investigación Fitoquímica, Pontificia Universidad Javeriana, Bogotá, Colombia.
Heliyon. 2022 Mar 25;8(3):e09182. doi: 10.1016/j.heliyon.2022.e09182. eCollection 2022 Mar.
Chagas disease, a worldwide public health concern, is a chronic infection caused by . Considering chronic persistence correlates with CD4 and CD8 T cell dysfunction and the safety and efficacy profiles of Benznidazol and Nifurtimox, the two drugs currently used for its etiological treatment, are far from ideal, the search of new trypanocidal treatment options is a highly relevant issue. Therefore, the objective of this work was to evaluate the trypanocidal effect and cytokine production induction of three extracts (hexane, dichloromethane and hydroalcoholic) obtained from , a plant traditionally used as a febrifuge in Colombia. Additionally, the extracts' major components with the highest trypanocidal activity were determined. It was evidenced hexane extract exhibited the highest activity capable of inhibiting the three parasite developmental stages with an IC/EC of 153.9 ± 29.5 (epimastigotes), 39.3 ± 7.2 (trypomastigotes), and 45.6 ± 10.5 (amastigotes) μg/mL, presenting a low cytotoxicity in VERO cells with a selectivity index ranging from 6.49 to 25.4. Moreover, this extract induced trypomastigote apoptotic death and inhibited parasite cell infection. The extract also induced IFN-γ and TNF production in CD4 and CD8 T cells, as well as production of the cytotoxic molecules granzyme B and perforin in CD8 T cells from healthy donors. Fatty acids and terpenes represented key compounds. Thus, the trypanocidal activity and cytokine production induction of the hexane extract may be associated with terpene presence, particularly, triterpenes.
恰加斯病是一个全球公共卫生问题，是由……引起的慢性感染。鉴于慢性持续性与CD4和CD8 T细胞功能障碍相关，且目前用于其病原治疗的两种药物苯硝唑和硝呋替莫的安全性和有效性并不理想，寻找新的杀锥虫治疗方案是一个高度相关的问题。因此，本研究的目的是评估从……中获得的三种提取物（己烷、二氯甲烷和水醇提取物）的杀锥虫效果和诱导细胞因子产生的能力，……是一种在哥伦比亚传统上用作退烧药的植物。此外，还确定了具有最高杀锥虫活性的提取物的主要成分。结果表明，己烷提取物表现出最高活性，能够抑制寄生虫的三个发育阶段，其对前鞭毛体、锥鞭毛体和无鞭毛体的半数抑制浓度/半数有效浓度分别为153.9±29.5、39.3±7.2和45.6±10.5μg/mL，在VERO细胞中具有低细胞毒性，选择性指数范围为6.49至25.4。此外，该提取物可诱导锥鞭毛体凋亡死亡并抑制寄生虫细胞感染。该提取物还可诱导健康供体CD4和CD8 T细胞产生IFN-γ和TNF，以及CD8 T细胞产生细胞毒性分子颗粒酶B和穿孔素。脂肪酸和萜类是关键化合物。因此，己烷提取物的杀锥虫活性和诱导细胞因子产生的能力可能与萜类的存在有关，特别是三萜类。
