Instituto de Farmacologia y Morfofisiologia, Facultad de Ciencias Veterinarias, Universidad Austral de Chile, Valdivia, Chile; Institute of Parasitology, Department of Pathobiology, University of Veterinary Medicine Vienna, 1210 Vienna, Austria.
Instituto de Farmacologia y Morfofisiologia, Facultad de Ciencias Veterinarias, Universidad Austral de Chile, Valdivia, Chile.
Int J Parasitol Drugs Drug Resist. 2022 Dec;20:43-53. doi: 10.1016/j.ijpddr.2022.08.002. Epub 2022 Aug 13.
Chagas disease, caused by the protozoa Trypanosoma cruzi, is a potentially life-threatening parasitic zoonosis infecting 6-7 million people worldwide, mainly in Latin America. Due to the limited numbers of drugs available against this neglected disease and their frequent adverse effects, novel anti-chagasic agents are urgently needed. Cichorium intybus L. (chicory) is a bioactive plant with potent activity against parasitic nematodes, but its effects on protozoans are poorly known and no studies have explored its trypanocidal potential. Here, we investigated the activity of C. intybus against extracellular and intracellular stages of T. cruzi, including the prediction of trypanocidal compounds by metabolomic analyses and bioactivity-based molecular networking. Purified C. intybus extracts were prepared from leaves and roots of five C. intybus cultivars (cv. 'Benulite', 'Goldine', 'Larigot', 'Maestoso' and 'Spadona'). All C. intybus extracts induced concentration-dependent effects against T. cruzi trypomastigotes. C. intybus leaf extracts had higher trypanocidal selectivity and lower cytotoxicity on mammalian cells than root extracts. The leaf extract of C. intybus cv. Goldine also significantly reduced the number of mammalian cells infected with T. cruzi amastigotes. Metabolomic and bioactivity-based molecular networking analyses revealed 11 compounds in C. intybus leaves strongly linked with activity against trypomastigotes, including the sesquiterpene lactone lactucin, and flavonoid- and fatty acid-derivatives. Furthermore, seven distinct C. intybus molecules (including two sesquiterpene lactone-derivatives) were predicted to be involved in reducing the number of mammalian cells infected with amastigotes. This is the first report of the anti-protozoal activity of C. intybus against trypanosomatid parasites and expands our understanding of the anti-parasitic effects of this plant and its bioactive metabolites. Further studies to elucidate the anti-protozoal compound(s) in C. intybus and their mode(s) of action will improve our knowledge of using this bioactive plant as a promising source of novel broad-spectrum anti-parasitic compounds with associated health benefits and biomedical potential.
克氏锥虫病由原生动物克氏锥虫引起，是一种潜在的危及生命的寄生虫性动物传染病，全球有 600 至 700 万人感染，主要分布在拉丁美洲。由于针对这种被忽视疾病的药物数量有限，且其经常产生不良反应，因此迫切需要新型抗锥虫药物。菊苣（菊苣）是一种具有强效抗寄生虫线虫活性的生物活性植物，但人们对其原生动物的作用知之甚少，也没有研究探索其杀锥虫潜力。在这里，我们研究了菊苣对克氏锥虫的细胞外和细胞内阶段的活性，包括通过代谢组学分析和基于生物活性的分子网络预测杀锥虫化合物。从菊苣的五种栽培品种（cv。'Benulite'、'Goldine'、'Larigot'、'Maestoso'和'Spadona'）的叶和根部分离出纯化的菊苣提取物。所有菊苣提取物均能诱导克氏锥虫游离体浓度依赖性的杀锥虫作用。菊苣叶提取物对哺乳动物细胞的杀锥虫选择性和细胞毒性均高于根提取物。菊苣 cv。Goldine 的叶提取物还显著减少了感染克氏锥虫无鞭毛体的哺乳动物细胞数量。代谢组学和基于生物活性的分子网络分析表明，菊苣叶中 11 种化合物与抗游离体活性密切相关，包括倍半萜内酯乳浆素以及黄酮类和脂肪酸衍生物。此外，预测有七种不同的菊苣分子（包括两种倍半萜内酯衍生物）参与减少感染无鞭毛体的哺乳动物细胞数量。这是首次报道菊苣对原生动物寄生虫的抗原生动物活性，并扩展了我们对这种植物及其生物活性代谢物的抗寄生虫作用的认识。进一步研究阐明菊苣中的抗原生动物化合物及其作用方式，将提高我们对将这种生物活性植物作为新型广谱抗寄生虫化合物的有希望来源的认识，这种化合物具有相关的健康益处和生物医学潜力。
