Alanazi Abdullah D, Alghabban Areej Jameel
Department of Biological Sciences, Faculty of Science and Humanities, Shaqra University, P.O. Box 1040, Ad-Dawadimi, 11911, Saudi Arabia.
Department of Biology, Faculty of Science, University of Tabuk, Saudi Arabia.
Int J Parasitol Drugs Drug Resist. 2024 Dec;26:100571. doi: 10.1016/j.ijpddr.2024.100571. Epub 2024 Nov 16.
Cutaneous leishmaniasis (CL) is a widespread disease affecting both humans and animals globally. Currently, common treatments (e.g., glucantime (GC) for CL treatment have many side effects that limit their use. The current experimental study aims to assess the in vitro, in vivo, and potential mechanisms of action of Rhanterium epapposum essential oil (REE) and its main compounds β-Myrcene (MC), camphene (CP), and limonene (LN) alone and in combination against Leishmania major. In vitro effects of REE and its main compounds were evaluated on amastigote forms, infection in macrophages cells stimulation of nitric oxide (NO), and stimulation of the cellular immunity in macrophages. In vivo efficacy of REE and its main constituents was also assessed in mice with CL through evaluating parasite burden, oxidative stress and proinflammatory-related genes. A concentration-dependent reduction in the average number of amastigotes was observed, with statistical significance (p < 0.001); whereas the results revealed synergistic effects when REE, MC and LN were combined with GC. REE and main compounds mainly in combination elicited a dose-dependent elevation in NO production and the expression levels of inducible nitric oxide synthase (iNOS), interferon gamma (IFN-γ), and tumor necrosis factor (TNF-α) genes in macrophages. Notably, mice treated with a combination of REE, MC, and GC showed the complete recovery of CL lesions after 28 days of treatment and resulted in a reduction of tissue malondialdehyde levels and a significant increase (p < 0.001) in the gene expression levels of the antioxidant enzymes. Topical treating CL-infected mice with REE and its main compounds alone particularly in conjunction with GC, significantly increased (p < 0.001) the expression levels of IFN-γ and interleukin (IL-12), while also causing a notable reduction in IL-4 expression. The findings of the current experimental research revealed the high in vitro and in vivo antileishmanial efficacy of REE and its main compounds MC, CP, and LN mainly in combination with GC; which indicated the high synergic effects of these compounds.
皮肤利什曼病（CL）是一种在全球范围内影响人类和动物的广泛疾病。目前，常见的治疗方法（如用于治疗CL的葡糖胺聚糖（GC））有许多副作用，限制了它们的使用。当前的实验研究旨在评估刺山柑精油（REE）及其主要化合物β-月桂烯（MC）、莰烯（CP）和柠檬烯（LN）单独及联合作用于硕大利什曼原虫的体外、体内作用及潜在作用机制。评估了REE及其主要化合物对无鞭毛体形式、巨噬细胞感染、一氧化氮（NO）刺激以及巨噬细胞细胞免疫刺激的体外作用。还通过评估寄生虫负荷、氧化应激和促炎相关基因，在CL小鼠中评估了REE及其主要成分的体内疗效。观察到无鞭毛体平均数量呈浓度依赖性减少，具有统计学意义（p < 0.001）；而结果显示，当REE、MC和LN与GC联合使用时具有协同作用。REE及其主要化合物主要联合使用可引起巨噬细胞中NO产生以及诱导型一氧化氮合酶（iNOS）、干扰素γ（IFN-γ）和肿瘤坏死因子（TNF-α）基因表达水平呈剂量依赖性升高。值得注意的是，用REE、MC和GC联合治疗的小鼠在治疗28天后CL病变完全恢复，导致组织丙二醛水平降低，抗氧化酶基因表达水平显著升高（p < 0.001）。单独用REE及其主要化合物局部治疗CL感染的小鼠，特别是与GC联合使用时，显著提高（p < 0.001）了IFN-γ和白细胞介素（IL-12）的表达水平，同时也使IL-4表达显著降低
