Lantana camara L. induces a multi-targeted cell death process in Leishmania amazonensis

• Published in: Journal of ethnopharmacology 2025-01, Vol.337 (Pt 1), p.118766, Article 118766
• Main Authors: Lemos, Ari Sérgio de Oliveira, Granato, Juliana da Trindade, Antinarelli, Luciana Maria Ribeiro, Machado, Patrícia de Almeida, Campos, Lara Melo, Bastos, João Pedro Reis Costa, Midlej, Victor do Valle, Silva Neto, Adolfo Firmino da, Fabri, Rodrigo Luiz, Coimbra, Elaine Soares
• Format: Article
• Language: English
• Subjects: Animals; Antiprotozoal Agents - isolation & purification; Antiprotozoal Agents - pharmacology; Cell Death - drug effects; Cellular death; Lantana - chemistry; Lantana camara; Leishmania - drug effects; Leishmania mexicana - drug effects; Leishmaniasis; Lipid metabolism; Macrophages - drug effects; Macrophages - parasitology; Mice; Mice, Inbred BALB C; Oxidative stress; Plant Extracts - chemistry; Plant Extracts - pharmacology; Plant Leaves - chemistry; Reactive Oxygen Species - metabolism; Verbenaceae
• ISSN: 0378-8741; 1872-7573; 1872-7573
• DOI: 10.1016/j.jep.2024.118766

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 IC50 values of 12.20 μg/mL ± 0.12 and 7.09 μg/mL ± 1.24, respectively. These IC50 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 (IC50 = 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, H2DCFDA, 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 un