Department of Parasitology, Microbiology and Immunology, Federal University of Juiz de Fora, Juiz de Fora, MG, 36036-900, Brazil.
Bioactive Natural Products Laboratory, Department of Biochemistry, Biological Sciences Institute, Federal University of Juiz de Fora, Juiz de Fora, Minas Gerais, CEP 36036-900, Brazil.
J Ethnopharmacol. 2025 Jan 30;337(Pt 1):118766. doi: 10.1016/j.jep.2024.118766. Epub 2024 Sep 1.
Lantana camara L. is a species known for its broad spectrum of bioactivities and is commonly used in folk therapy to address inflammatory, dermatological, gastrointestinal, intestinal worms and protozoan diseases. It boasts a diverse array of secondary metabolites such as terpenes, flavonoids, and saponins. However, despite its rich chemical profile, there remains a scarcity of studies investigating its antileishmanial properties.
This research aims to explore the antileishmanial potential of L. camara, focusing also on its mechanism of action against Leishmania amazonensis.
The ethanolic extract of L. camara leaves (LCE) was obtained through static maceration, and its phytoconstituents were identified using UFLC-QTOF-MS. The colorimetric MTT method was conducted to determine the effect of LCE on promastigotes of L. amazonensis and murine macrophages. The anti-amastigote activity was evaluated by counting intracellular parasites in macrophages after Giemsa staining. Additionally, investigations into the mechanisms underlying its action were conducted using cellular and biochemical approaches.
LCE exhibited significant activity against both promastigotes and intracellular amastigotes of L. amazonensis, with IC values of 12.20 μg/mL ± 0.12 and 7.09 μg/mL ± 1.24, respectively. These IC values indicate very promising antileishmanial activity, comparable to those found for the positive control miltefosine (5.10 μg/mL ± 1.79 and 8.96 μg/mL ± 0.50, respectively). Notably, LCE exhibited negligible cytotoxicity on macrophages (IC = 223.40 μg/mL ± 47.02), demonstrating selectivity towards host cells (SI = 31.50). The antileishmanial activity of LCE involved a multi-targeted cell death process, characterized by morphological and ultrastructural alterations observed through SEM and TEM analyses, as well as oxidative effects evidenced by the inhibition of trypanothione reductase, elevation of ROS and lipid levels, and mitochondrial dysfunction evaluated using DTNB, HDCFDA, Nile red, and JC-1 assays. Additionally, extraction of ergosterol and double labeling with annexin V and PI revealed modifications to the organization and permeability of the treated parasite's plasma membrane. LCE was found to consist predominantly of terpenes, with lantadenes A, B, and C being among the eleven compounds identified through UFLC-QTOF-MS analysis.
The extract of L. camara presents a diverse array of chemical constituents, prominently featuring high terpene content, which may underlie its antileishmanial properties through a combination of apoptotic and non-apoptotic mechanisms of cell death induced by LCE. This study underscores the therapeutic potential of L. camara as a candidate for antileishmanial treatment, pending further validation.
马缨丹属植物因具有广泛的生物活性而闻名，常用于民间疗法来治疗炎症、皮肤病、胃肠道、肠道蠕虫和原生动物疾病。它拥有多种多样的次生代谢产物，如萜类、类黄酮和皂苷。然而，尽管其化学物质种类丰富，但对于其抗利什曼原虫的特性研究仍然相对较少。
本研究旨在探索马缨丹属植物的抗利什曼原虫潜力，同时关注其对利什曼原虫亚马逊亚种的作用机制。
通过静态浸提法从马缨丹属植物的叶子中提取乙醇提取物（LCE），并使用 UFLC-QTOF-MS 鉴定其植物成分。采用 MTT 比色法测定 LCE 对利什曼原虫亚马逊亚种的前鞭毛体和鼠源巨噬细胞的影响。通过吉姆萨染色后对巨噬细胞内的内寄生虫进行计数来评估抗内寄生虫活性。此外，还通过细胞和生化方法研究其作用机制。
LCE 对利什曼原虫亚马逊亚种的前鞭毛体和内寄生虫均表现出显著的活性，IC 值分别为 12.20μg/mL±0.12 和 7.09μg/mL±1.24。这些 IC 值表明其具有非常有前景的抗利什曼原虫活性，与阳性对照米替福新（5.10μg/mL±1.79 和 8.96μg/mL±0.50）相当。值得注意的是，LCE 对巨噬细胞的细胞毒性可忽略不计（IC=223.40μg/mL±47.02），表现出对宿主细胞的选择性（SI=31.50）。LCE 的抗利什曼原虫活性涉及多靶点细胞死亡过程，通过 SEM 和 TEM 分析观察到形态和超微结构的改变，以及通过抑制三磷酸鸟苷还原酶、升高 ROS 和脂质水平以及使用 DTNB、HDCFDA、尼罗红和 JC-1 测定评估线粒体功能来证明氧化作用。此外，从麦角固醇的提取和与 annexin V 和 PI 的双重标记揭示了处理后的寄生虫质膜的组织和通透性的改变。通过 UFLC-QTOF-MS 分析，发现 LCE 主要由萜类化合物组成，其中包括 11 种化合物，分别为 lan-tadenes A、B 和 C。
马缨丹属植物的提取物含有多种化学物质，其中萜类化合物含量较高，这可能是通过 LCE 诱导的凋亡和非凋亡细胞死亡机制的组合，为其抗利什曼原虫特性提供了基础。本研究强调了马缨丹属植物作为抗利什曼原虫治疗候选物的治疗潜力，但仍需进一步验证。
