In Vitro and In Vivo Effectiveness of Carvacrol, Thymol and Linalool against Leishmania infantum

香芹酚、百里酚和芳樟醇对利什曼原虫的体外和体内疗效

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作者:Mohammad Reza Youssefi, Elham Moghaddas, Mohaddeseh Abouhosseini Tabari, Ali Akbar Moghadamnia, Seyed Mohammad Hosseini, Bibi Razieh Hosseini Farash, Mohammad Amin Ebrahimi, Niki Nabavi Mousavi, Abdolmajid Fata, Filippo Maggi, Riccardo Petrelli, Stefano Dall'Acqua, Giovanni Benelli, Stefania Sut6

Background

One of the most important causative agents of visceral leishmaniasis (VL) is Leishmania infantum, which is mainly spread by Phlebotomus and Lutzomyia sandflies in the Old and New World, respectively. Novel and effective drugs to manage this neglected vector-borne disease are urgently required. In this study, we evaluated the toxicity of carvacrol, thymol and linalool, three common essential oil constituents, on amastigotes and promastigotes of L. infantum.

Conclusions

Overall, thymol and carvacrol are highly promising candidates for the development of effective and safe drugs in the fight against VL.

Methods

in vitro experiments were performed by 24 h MTT assay. Carvacrol, thymol and linalool at concentrations ranging from 1.3 to 10 μg/mL were tested on promastigotes of L. infantum. For in vivo test, two groups of hamsters (Mesocricetus auratus) received 100 mg/kg of body weight/day of carvacrol and thymol as intraperitoneal injection on day 7 post-infection, followed by a 48 h later injection. The third group was treated with the glucantime as standard drug (500 mg/kg) and the last group (control) just received normal saline. On the 16th day, the number of parasites and histopathological changes in liver and spleen were investigated.

Results

24 h MTT assay showed promising antileishmanial activity of thymol and carvacrol, with IC50 values of 7.2 (48 μM) and 9.8 μg/mL (65 μM), respectively. Linalool at all concentrations did not affect L. infantum promastigote viability. In vivo toxicity data of carvacrol and thymol showed that the former at 100 mg/kg was the safest and most effective treatment with little side effects on the liver. Conclusions: Overall, thymol and carvacrol are highly promising candidates for the development of effective and safe drugs in the fight against VL.

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