The cytotoxic and anti-leishmanial activity of Oregano (Origanum vulgare) essential oil: An in vitro, in vivo, and in silico study

This study was aimed at investigating the leishmanicidal and immunomodulatory of oregano essential oil (OEO) from Origanum vulgare on experimental Leishmania amazonensis-model through in silico, in vitro, and in vivo approaches. For this purpose, drug-likeness prediction of OEO main components in silico was assessed, the leishmanicidal activity against promastigotes and amastigote-infected macrophages, as well its microbicide and immunomodulatory mechanisms in vitro, and the in vivo treatment on L. amazonensis-infected mice. It was demonstrated that OEO containing carvacrol, thymol, gamma-terpinene, p-cymene, and beta-caryophyllene as the main components is a good candidate for oral and topical drug development according to the in silico study, acting against L. amazonensis in vitro and in vivo in murine model. OEO acted on promastigote forms, triggering a combination of autophagic, apoptotic, and necrotic events, as well as in intramacrophagic amastigote forms, without triggering a pro-inflammatory response, showing reduced TNF-alpha, reactive oxygen species, and nitric oxide levels with high arginase-1/iNOS ratio. The in vivo study confirmed the OEO anti-leishmanial potential, reducing the lesions of infected mice. Computational docking analysis suggested the arginase-carvacrol interactions by spontaneous binding proposing probable antileishmanial targets of OEO. The study provided new perspectives to the OEO treatment, showing its effect against L. amazonensis, providing support for further studies of antileishmanial drugs.