Barbosa Flávia Eduarda Vidal, de Lima Dimas Batista, Dos Santos Ana Lúcia Estevam, de Sousa Valéria Carlos, de Cássia Viana Carvalho Rita, de Moraes Alves Michel Mualém, de Lima Marcos Antônio Pereira, da Silva Souza Racquel Oliveira, da Silva Cláudio Gleidiston Lima, Teixeira Claudener Souza
Faculty of Medicine, Federal University of Cariri, CE, Brazil.
Laboratory of anti-leishmanial activity, Federal University of Piauí, PI, Brazil.
Int J Biol Macromol. 2024 Sep 14;280(Pt 1):135665. doi: 10.1016/j.ijbiomac.2024.135665.
Despite promising advancements in leishmaniasis treatment, existing therapies often face limitations and significant side effects, stimulating the search for novel therapeutic alternatives. In this context, lectins, such as DVL extracted from Dioclea violacea seeds, have emerged as potential candidates due to their diverse biological activities. This study represents the first investigation of the leishmanicidal potential of DVL in vitro against Leishmania infantum. Our results demonstrate that DVL exhibits a leishmanicidal effect (IC/24 h = 49.37 μg/mL or 2 μM), binding to glycans on L. infantum. Fluorescence assays revealed that DVL can induce the production of reactive oxygen species (ROS) and cause damage to the parasite's membrane. DVL demonstrated a modulating effect when combined with amphotericin B and glucantime, enhancing the activity of these drugs by 40 % and 80 %, respectively. It also showed no cytotoxicity in Raw 264.7 cells and was able to override the toxic effect of amphotericin B on cells and reduce the survival rate of macrophages infected with amastigote forms, as well as their percentage of infection by 31 %. Therefore, DVL shows promise as a treatment for visceral leishmaniasis caused by L. infantum. Our findings provide valuable insights for future therapeutic development targeting leishmania glycans.
尽管利什曼病治疗取得了有前景的进展,但现有疗法常常面临局限性和显著的副作用,这促使人们寻找新的治疗选择。在此背景下,诸如从紫花蝶豆种子中提取的DVL等凝集素,因其多样的生物活性而成为潜在的候选物。本研究首次调查了DVL体外对婴儿利什曼原虫的杀利什曼原虫潜力。我们的结果表明,DVL表现出杀利什曼原虫作用(IC/24小时 = 49.37 μg/mL或2 μM),与婴儿利什曼原虫上的聚糖结合。荧光测定显示,DVL可诱导活性氧(ROS)的产生并对寄生虫膜造成损伤。DVL与两性霉素B和葡糖胺锑联合使用时表现出调节作用,分别将这些药物的活性提高了40%和80%。它在Raw 264.7细胞中也未显示出细胞毒性,并且能够克服两性霉素B对细胞的毒性作用,降低感染无鞭毛体形式的巨噬细胞的存活率及其感染百分比31%。因此,DVL有望成为治疗由婴儿利什曼原虫引起的内脏利什曼病的药物。我们的研究结果为未来针对利什曼原虫聚糖的治疗开发提供了有价值的见解。