Carrillo-Aké Ana G, Delgado-Domínguez José, Cervantes-Sarabia Rocely Buenaventura, Ruiz-Remigio Adriana, Zamora-Chimal Jaime, Salaiza-Suazo Norma, Torres-Tapia Luis W, Peraza-Sánchez Sergio R, Becker Ingeborg
Unidad de Medicina Experimental, Facultad de Medicina, Universidad Nacional Autónoma de México (UNAM), Hospital General de México Dr. Balmis 148, Ciudad de México 06720, Mexico.
Centro de Investigación Científica de Yucatán (CICY), Unidad de Biotecnología, Calle 43 #130, Col. Chuburná de Hidalgo, Mérida, Yucatán 97205, Mexico.
J Nat Prod. 2025 Apr 25;88(4):959-966. doi: 10.1021/acs.jnatprod.4c01411. Epub 2025 Apr 3.
Pentavalent antimonials are the first-line treatment for localized cutaneous leishmaniasis. However, they have disadvantages such as their elevated toxicity, high costs, and parenteral application. Plant-derived compounds may be an alternative treatment against this disease. Previous studies have shown that (3)-16,17-didehydrofalcarinol (), a polyacetylene oxylipin isolated from , is active against . We have analyzed the mechanism of action of compound , evaluating reactive oxygen species production, apoptosis of , cytotoxicity in murine macrophages, and its efficacy in controlling the disease progression and parasite load when applied topically in C57BL/6 mice infected with . Results show that parasites incubated with 1.6 μM compound significantly increased reactive oxygen species production ( ≤ 0.05). The percentage of apoptosis also increased significantly ( ≤ 0.05) and did not affect the viability of macrophages. The application of the topical formulations with 0.5% and 0.75% compound for 7 weeks reduced disease progression and parasite load. We demonstrate that compound generates the death of by apoptosis through reactive oxygen species production. We conclude that compound can be used a possible alternative treatment for localized cutaneous leishmaniasis, enabling a less painful and more accessible therapy.
五价锑化合物是局部皮肤利什曼病的一线治疗药物。然而,它们存在一些缺点,如毒性较高、成本高昂以及需要肠胃外给药。植物衍生化合物可能是治疗这种疾病的一种替代方法。先前的研究表明,从[具体植物]中分离出的一种聚乙炔氧化脂质(3)-16,17-二脱氢法卡林醇([化合物名称])对[病原体名称]具有活性。我们分析了化合物[化合物名称]的作用机制,评估了活性氧的产生、[细胞名称]的凋亡、对小鼠巨噬细胞的细胞毒性,以及在局部应用于感染[病原体名称]的C57BL/6小鼠时,其在控制疾病进展和寄生虫负荷方面的功效。结果表明,用1.6 μM化合物[化合物名称]孵育的寄生虫显著增加了活性氧的产生(P≤0.05)。凋亡百分比也显著增加(P≤0.05),且未影响巨噬细胞的活力。使用含0.5%和0.75%化合物[化合物名称]的局部制剂治疗7周可减轻疾病进展并降低寄生虫负荷。我们证明化合物[化合物名称]通过产生活性氧诱导[细胞名称]凋亡而死亡。我们得出结论,化合物[化合物名称]可作为局部皮肤利什曼病的一种可能替代治疗方法,提供一种痛苦较小且更易获得的治疗方式。