Grupo de Enfermedades Infecciosas, Facultad de Ciencias, Pontificia Universidad Javeriana, Bogotá, Colombia.
Grupo de Inmunobiología y Biología Celular, Pontificia Universidad Javeriana, Bogotá, Colombia.
Exp Parasitol. 2021 Apr;223:108079. doi: 10.1016/j.exppara.2021.108079. Epub 2021 Jan 29.
Chagas disease is caused by Trypanosoma cruzi, and it is an important cause of morbidity and mortality in Latin America. There are no vaccines, and the chemotherapy available to treat this infection has serious side effects. In a search for alternative treatments, we determined the in vitro susceptibility of epimastigote and trypomastigote forms of T. cruzi and the cytotoxic effects on peripheral blood mononuclear cells (PBMCs) of ethanolic extracts obtained from six different plant species. The ethanolic extracts of Ageratina vacciniaefolia, Clethra fimbriata and Siparuna sessiliflora showed antiprotozoal activity against epimastigotes and low cytotoxicity in mammalian cells. However, only the ethanolic extract of C. fimbriata showed activity against T. cruzi trypomastigotes, and it had low cytotoxicity in PBMCs. An analysis on the phytochemical composition of C. fimbriata extract showed that its metabolites were primarily represented by two families of compounds: flavonoids and terpenoids. Lastly, we analyzed whether the A. vacciniaefolia, C. fimbriata, or S. sessiliflora ethanolic extracts induced IFN-γ or TNF-α production. Significantly, ethanolic extracts of C. fimbriata induced TNF-α production and S. sessiliflora induced both cytokines. In addition, C. fimbriata and S. sessiliflora induced the simultaneous secretion of IFN-γ and TNF-α in CD8 T cells. The antiprotozoal and immunomodulatory activity of C. fimbriata may be related to the presence of flavonoid and triterpene compounds in the extract. Thus, these findings suggest that C. fimbriata may represent a valuable source of new bioactive compounds for the therapeutic treatment of Chagas disease that combines trypanocidal activity with the capacity to boost the immune response.
克氏锥虫病是由克氏锥虫引起的,是拉丁美洲发病率和死亡率的重要原因。目前尚无疫苗可用,可用于治疗这种感染的化疗药物有严重的副作用。在寻找替代治疗方法的过程中,我们确定了克氏锥虫的前鞭毛体和变形体形式的体外敏感性,以及从六种不同植物物种获得的乙醇提取物对外周血单核细胞(PBMC)的细胞毒性作用。Ageratina vacciniaefolia、Clethra fimbriata 和 Siparuna sessiliflora 的乙醇提取物对前鞭毛体具有抗原生动物活性,对哺乳动物细胞的细胞毒性低。然而,只有 C. fimbriata 的乙醇提取物对克氏锥虫变形体具有活性,并且对 PBMC 的细胞毒性低。C. fimbriata 提取物的植物化学成分分析表明,其代谢物主要由两类化合物组成:类黄酮和萜类化合物。最后,我们分析了 A. vacciniaefolia、C. fimbriata 或 S. sessiliflora 乙醇提取物是否诱导 IFN-γ 或 TNF-α 的产生。值得注意的是,C. fimbriata 的乙醇提取物诱导 TNF-α 的产生,而 S. sessiliflora 诱导两种细胞因子。此外,C. fimbriata 和 S. sessiliflora 诱导 CD8 T 细胞同时分泌 IFN-γ 和 TNF-α。C. fimbriata 的抗原生动物和免疫调节活性可能与其提取物中存在类黄酮和三萜化合物有关。因此,这些发现表明 C. fimbriata 可能是一种有价值的新生物活性化合物来源,可用于治疗锥虫病,其结合了杀锥虫活性和增强免疫反应的能力。