Nápoles Rodríguez Rachel, Arreguez María Laura, Corlatti Aldana M, Bach Hernán G, Catalán César A N, Laurella Laura C, Barroso Paola A, Sülsen Valeria P
CONICET-Universidad de Buenos Aires, Instituto de Química y Metabolismo del Fármaco (IQUIMEFA), Autonomous City of Buenos Aires C1113AAD, Argentina.
CONICET-Universidad Nacional de Salta, Instituto de Patología Experimental (IPE), Salta A4400, Argentina.
Molecules. 2025 Feb 24;30(5):1039. doi: 10.3390/molecules30051039.
Leishmaniasis is a neglected tropical disease caused by protozoan parasites of the genus . An estimated 700,000 to 1 million new cases occur annually. Current therapies are limited by high toxicity, cost, prolonged treatment period, and rising resistance in endemic regions. The Asteraceae family has emerged as a promising source of bioactive compounds with proven leishmanicidal activity. In this study, the assessment of the antileishmanial activity of and extracts, the isolation of the sesquiterpene lactones heliangin and glaucolide A, respectively, and the evaluation of the activity of the compounds were conducted. Dichloromethane extracts of and were active on promastigotes, inhibiting the replication of the parasites in 97.2 ± 3.1% and 89.1 ± 1.1%, respectively, at 100 μg/mL. Heliangin was active against promastigotes of (IC = 9.3 μM) and intracellular amastigotes (IC = 0.8 μM), while glaucolide A exhibited moderate activity against promastigotes (IC = 46.7 μM) and did not show activity against intracellular amastigotes. Based on these results, heliangin was further evaluated in an animal model of cutaneous leishmaniasis using BALB/c mice infected with . Heliangin (8 mg/Kg), when administered in combination with Glucantime, significantly reduced lesion progression and parasite load compared to the vehicle-treated group ( < 0.001). These findings show that heliangin is a potential candidate for leishmaniasis treatment, especially in combination with therapeutic drugs.
利什曼病是一种由利什曼原虫属原生动物寄生虫引起的被忽视的热带疾病。据估计，每年有70万至100万新病例出现。目前的治疗方法受到高毒性、高成本、治疗期延长以及流行地区耐药性上升的限制。菊科已成为具有已证实的杀利什曼活性的生物活性化合物的有前景的来源。在本研究中，对[植物名称1]和[植物名称2]提取物的抗利什曼活性进行了评估，分别分离出倍半萜内酯海良内酯和格劳可内酯A，并对这些化合物的活性进行了评估。[植物名称1]和[植物名称2]的二氯甲烷提取物对[利什曼原虫种类1]前鞭毛体有活性，在100μg/mL时分别抑制寄生虫复制97.2±3.1%和89.1±1.1%。海良内酯对[利什曼原虫种类1]前鞭毛体（IC50 = 9.3μM）和细胞内无鞭毛体（IC50 = 0.8μM）有活性，而格劳可内酯A对前鞭毛体表现出中等活性（IC50 = 46.7μM），对细胞内无鞭毛体无活性。基于这些结果，使用感染[利什曼原虫种类1]的BALB/c小鼠在皮肤利什曼病动物模型中对海良内酯进行了进一步评估。与赋形剂处理组相比，海良内酯（8mg/Kg）与葡糖胺联合给药时，显著降低了病变进展和寄生虫载量（P < 0.001）。这些发现表明，海良内酯是利什曼病治疗的潜在候选药物，特别是与治疗药物联合使用时。
