Departament of Microbiology and Parasitology, School of Pharmacy, Universidad Complutense de Madrid, Plaza Ramón y Cajal s/n, 28040 Madrid, Spain.
Laboratorio de Parasitología y Entomología INLASA, Pasaje Rafael Zubieta #1889, (Lado Estado Mayor del ejército) Zona Miraflores, La Paz, Bolivia.
Molecules. 2020 Mar 19;25(6):1394. doi: 10.3390/molecules25061394.
Leishmaniasis affects around 12 million people worldwide and is estimated to cause the ninth-largest disease burden. There are three main forms of the disease, visceral (VL), cutaneous (CL), and mucocutaneous (MCL), leading to more than one million new cases every year and several thousand deaths. Current treatments based on chemically synthesized molecules are far from ideal. In this study, we have tested the in vitro and in vivo efficacy of ursolic acid (UA), a multifunctional triterpenoid with well-known antitumoral, antioxidant, and antimicrobial effects on different strains. The in vitro antileishmanial activity against the intracellular forms was six and three-fold higher compared to extracellular forms of and respectively. UA also showed to be a potent antileishmanial drug against both VL and CL manifestations of the disease in experimental models. UA parenterally administered at 5 mg/kg for seven days significantly reduced the parasite burden in liver and spleen not only in murine acute infection but also in a chronic-infection model against . In addition, UA ointment (0.2%) topically administered for four weeks diminished (50%) lesion size progression in a chronic infection model of CL caused by which was much greater than the effect of UA formulated as an O/W emulsion. UA played a key role in the immunological response modulating the Th1 response. The exposure of infected macrophages to UA led to a significant different production in the cytokine levels depending on the strain causing the infection. In conclusion, UA can be a promising therapy against both CL and VL.
利什曼病影响全球约 1200 万人，估计其疾病负担在全球第九位。该病有三种主要形式，即内脏利什曼病（VL）、皮肤利什曼病（CL）和黏膜皮肤利什曼病（MCL），每年导致超过 100 万例新发病例和数千人死亡。目前基于化学合成分子的治疗方法远非理想。在这项研究中，我们测试了熊果酸（UA）的体外和体内疗效，UA 是一种具有多种功能的三萜类化合物，对不同菌株具有众所周知的抗肿瘤、抗氧化和抗菌作用。与 和 分别的细胞外形式相比，其对细胞内形式的抗利什曼原虫活性高 6 倍和 3 倍。UA 还显示出对实验模型中 VL 和 CL 表现形式的疾病具有强大的抗利什曼原虫作用。UA 以 5mg/kg 的剂量经肠胃外给药 7 天，不仅显著降低了肝和脾中的寄生虫负担，而且在针对 的慢性感染模型中也降低了寄生虫负担。此外，UA 软膏（0.2%）局部给药 4 周，显著减少了 CL 慢性感染模型（由 引起）中病变大小的进展（50%），这比 UA 制成 O/W 乳剂的效果大得多。UA 在调节 Th1 反应的免疫反应中发挥了关键作用。感染的巨噬细胞暴露于 UA 会导致根据引起感染的 菌株导致细胞因子水平产生显著不同的产生。总之，UA 可能是一种针对 CL 和 VL 的有前途的治疗方法。
