College of Pharmacy, University of Al-Muthana, Samawa, Almuthana, Iraq.
Department of Biology, College of Science, University of Baghdad, Al-Jaderiya Campus, Baghdad 10071, Iraq.
Cytokine. 2024 Nov;183:156757. doi: 10.1016/j.cyto.2024.156757. Epub 2024 Sep 16.
Visceral leishmaniasis is a neglected tropical disease that can be lethal if not treated. The available medicines have severe side effects, such as toxicity and drug resistance. Various investigations are looking into new anti-leishmanial compounds from natural products that have little impact on host cells. Lupeol, a triterpenoid present in the flora of many edible plants, has been shown to have antimicrobial properties. The present study investigated the immunomodulatory effects of lupeol on U937 macrophages infected with Leishmania donovani, focusing on the expression of key cytokines and enzymes involved in the immune response.
U937 macrophages were infected with Leishmania donovani amastigotes and treated with varying concentrations of lupeol throughout three days. The expression levels of inducible nitric oxide synthase (iNOS), tumor necrosis factor-alpha (TNF-α), and interleukin-10 (IL-10) were measured using real-time polymerase chain reaction (RT-PCR). A positive simulation of gene expression was estimated using ΔΔCT to assess relative expression.
The results demonstrated that lupeol significantly upregulated iNOS and TNF-α expression, especially at higher concentrations, indicating enhanced pro-inflammatory and anti-leishmanial activity. Interestingly, IL-10 expression also increased, suggesting a complex immunomodulatory role of lupeol that involves both pro-inflammatory and anti-inflammatory pathways. Pearson correlation analysis revealed a strong association between iNOS and TNF-α (0.97692), as well as a moderate correlation between iNOS and IL-10 (0.51603).
These findings suggest that lupeol may promote a balanced immune response, enhancing the body's ability to combat L. donovani while potentially mitigating excessive inflammation. Lupeol can potentially serve as a novel therapeutic agent against visceral leishmaniasis.
内脏利什曼病是一种被忽视的热带病，如果不治疗可能致命。现有的药物有严重的副作用，如毒性和耐药性。各种研究都在从天然产物中寻找新的抗利什曼原虫化合物，这些化合物对宿主细胞的影响较小。存在于许多食用植物中的三萜类化合物羽扇醇已被证明具有抗菌特性。本研究调查了羽扇醇对感染利什曼原虫的 U937 巨噬细胞的免疫调节作用，重点研究了参与免疫反应的关键细胞因子和酶的表达。
用利什曼原虫无鞭毛体感染 U937 巨噬细胞，在三天内用不同浓度的羽扇醇处理。用实时聚合酶链反应（RT-PCR）测量诱导型一氧化氮合酶（iNOS）、肿瘤坏死因子-α（TNF-α）和白细胞介素-10（IL-10）的表达水平。用 ΔΔCT 估计基因表达的正模拟，以评估相对表达。
结果表明，羽扇醇显著上调了 iNOS 和 TNF-α的表达，特别是在较高浓度下，表明增强了促炎和抗利什曼原虫活性。有趣的是，IL-10 的表达也增加了，这表明羽扇醇具有复杂的免疫调节作用，涉及促炎和抗炎途径。Pearson 相关分析显示 iNOS 和 TNF-α（0.97692）之间存在很强的相关性，iNOS 和 IL-10（0.51603）之间存在中度相关性。
这些发现表明，羽扇醇可能促进了平衡的免疫反应，增强了机体对抗 L. donovani 的能力，同时可能减轻过度炎症。羽扇醇可能成为治疗内脏利什曼病的一种新的治疗剂。
