Aksoy Tülay, Kilimcioğlu Ali Ahmet
Inonu University, Medical Faculty, Department of Parasitology, Malatya, Türkiye.
Manisa Celal Bayar University, Medical Faculty, Department of Parasitology, Manisa, Türkiye.
Parasitol Int. 2026 Feb;110:103139. doi: 10.1016/j.parint.2025.103139. Epub 2025 Aug 6.
Cutaneous leishmaniasis (CL) is a neglected tropical disease associated with significant morbidity, primarily due to chronic skin lesions, scarring, and psychosocial consequences. This study aimed to investigate the in vitro and ex vivo antileishmanial effects of thymol (1-500 μM) against Leishmania tropica (MHOM/TR/2012/CBCL-LT) infection. Thymol's in vitro efficacy was assessed on both promastigote (Haemocytometry and CellTiter-Glo assays) and amastigote (Giemsa staining and Parasite Rescue Transformation Assay) forms of L. tropica. Additionally, its immunomodulatory effects were evaluated by analyzing cytokine secretion (IFN-γ, IL-12, IL-10, and IL-4) and infectivity in THP-1 macrophages using ELISA. Cytotoxicity was determined by calculating the 50 % cytotoxic concentration (CC) in THP-1 cells. The in vitro inhibitory concentration (IC) value against L. tropica promastigotes was determined as 79.41 μM, while the ex vivo IC value against amastigotes was 105.2 μM. Incubation of infected macrophages with thymol resulted in a dose-dependent increase in IFN-γ and IL-12 levels, along with a significant reduction in IL-10 and IL-4 secretion (p < 0.05). The CC value of thymol in THP-1 cells was 160.7 μM, indicating low cytotoxicity. Moreover, the selectivity index (SI) values greater than 1 confirmed the compound's preferential action against amastigotes while exhibiting minimal toxicity toward macrophages. These findings highlight thymol's potential as an antileishmanial agent by effectively eliminating and controlling Leishmania parasites in both in vitro and ex vivo models. Due to its immunomodulatory properties and low cytotoxicity, thymol represents a promising starting point for the development of novel antileishmanial agents and alternative therapeutic strategies against CL caused by L. tropica.
皮肤利什曼病（CL）是一种被忽视的热带疾病，主要因慢性皮肤损伤、瘢痕形成及社会心理后果而导致显著的发病率。本研究旨在调查百里香酚（1 - 500 μM）对热带利什曼原虫（MHOM/TR/2012/CBCL-LT）感染的体外和离体抗利什曼作用。通过血细胞计数法和CellTiter-Glo检测法评估百里香酚对热带利什曼原虫前鞭毛体的体外疗效，通过吉姆萨染色和寄生虫拯救转化试验评估对无鞭毛体的疗效。此外，通过酶联免疫吸附测定（ELISA）分析细胞因子分泌（IFN-γ、IL-12、IL-10和IL-4）以及在THP-1巨噬细胞中的感染性来评估其免疫调节作用。通过计算THP-1细胞中的50%细胞毒性浓度（CC）来确定细胞毒性。对热带利什曼原虫前鞭毛体的体外抑制浓度（IC）值确定为79.41 μM，而对无鞭毛体的离体IC值为105.2 μM。用百里香酚孵育感染的巨噬细胞导致IFN-γ和IL-12水平呈剂量依赖性增加，同时IL-10和IL-4分泌显著减少（p < 0.05）。百里香酚在THP-1细胞中的CC值为160.7 μM，表明细胞毒性较低。此外，大于1的选择性指数（SI）值证实了该化合物对无鞭毛体具有优先作用，同时对巨噬细胞表现出最小毒性。这些发现突出了百里香酚作为一种抗利什曼原虫剂的潜力，即在体外和离体模型中有效消除和控制利什曼原虫寄生虫。由于其免疫调节特性和低细胞毒性，百里香酚是开发新型抗利什曼原虫剂以及针对热带利什曼原虫引起的皮肤利什曼病的替代治疗策略的一个有前景的起点。
