In Vitro and In Vivo Effectiveness of Carvacrol, Thymol and Linalool against <i>Leishmania infantum</i>

Background: One of the most important causative agents of visceral leishmaniasis (VL) is <i>Leishmania infantum</i>, which is mainly spread by <i>Phlebotomus</i> and <i>Lutzomyia</i> sandflies in the Old and New World, respectively. Novel and effective drugs to ma...

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Main Authors: 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 Sut
Format: Article
Language:English
Published: MDPI AG 2019-05-01
Series:Molecules
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Online Access:https://www.mdpi.com/1420-3049/24/11/2072
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author 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 Sut
author_facet 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 Sut
author_sort Mohammad Reza Youssefi
collection DOAJ
description Background: One of the most important causative agents of visceral leishmaniasis (VL) is <i>Leishmania infantum</i>, which is mainly spread by <i>Phlebotomus</i> and <i>Lutzomyia</i> 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 <i>L. infantum</i>. <i>Methods</i>: in vitro experiments were performed by 24 h MTT assay. Carvacrol, thymol and linalool at concentrations ranging from 1.3 to 10 &#956;g/mL were tested on promastigotes of <i>L. infantum</i>. For in vivo test, two groups of hamsters (<i>Mesocricetus auratus</i>) 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 IC<sub>50</sub> values of 7.2 (48 &#956;M) and 9.8 &#956;g/mL (65 &#956;M), respectively. Linalool at all concentrations did not affect <i>L. infantum</i> 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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spelling doaj.art-c4f61827c77d4dabb056cd266d9a3c362022-12-21T22:21:11ZengMDPI AGMolecules1420-30492019-05-012411207210.3390/molecules24112072molecules24112072In Vitro and In Vivo Effectiveness of Carvacrol, Thymol and Linalool against <i>Leishmania infantum</i>Mohammad Reza Youssefi0Elham Moghaddas1Mohaddeseh Abouhosseini Tabari2Ali Akbar Moghadamnia3Seyed Mohammad Hosseini4Bibi Razieh Hosseini Farash5Mohammad Amin Ebrahimi6Niki Nabavi Mousavi7Abdolmajid Fata8Filippo Maggi9Riccardo Petrelli10Stefano Dall’Acqua11Giovanni Benelli12Stefania Sut13Department of Veterinary Parasitology, Babol-Branch, Islamic Azad University, Babol 8415683111, IranDepartment of Parasitology and Mycology, School of Medicine, Mashhad University of Medical Sciences, Mashhad 9177899191, IranFaculty of Veterinary Medicine, Amol University of Special Modern Technologies, Amol 46131, IranDepartment of Pharmacology, Babol University of Medical Sciences, Babol 8415683111, IranDepartment of Veterinary Pathology, Babol-Branch Islamic Azad University, Babol 8415683111, IranDepartment of Parasitology and Mycology, School of Medicine, Mashhad University of Medical Sciences, Mashhad 9177899191, IranYoung Researcher and Elite Club, Islamic Azad University, Babol-Branch, Babol 8415683111, IranYoung Researcher and Elite Club, Islamic Azad University, Babol-Branch, Babol 8415683111, IranDepartment of Parasitology and Mycology, School of Medicine, Mashhad University of Medical Sciences, Mashhad 9177899191, IranSchool of Pharmacy, University of Camerino, 62032 Camerino, ItalySchool of Pharmacy, University of Camerino, 62032 Camerino, ItalyDepartment of Pharmaceutical and Pharmacological Sciences, University of Padova, 35121 Padova, ItalyDepartment of Agriculture, Food and Environment, University of Pisa, via del Borghetto 80, 56124 Pisa, ItalyDepartment of Agronomy, Food, Natural Resources, Animals and Environment (DAFNAE), University of Padova, 35020 Legnaro, ItalyBackground: One of the most important causative agents of visceral leishmaniasis (VL) is <i>Leishmania infantum</i>, which is mainly spread by <i>Phlebotomus</i> and <i>Lutzomyia</i> 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 <i>L. infantum</i>. <i>Methods</i>: in vitro experiments were performed by 24 h MTT assay. Carvacrol, thymol and linalool at concentrations ranging from 1.3 to 10 &#956;g/mL were tested on promastigotes of <i>L. infantum</i>. For in vivo test, two groups of hamsters (<i>Mesocricetus auratus</i>) 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 IC<sub>50</sub> values of 7.2 (48 &#956;M) and 9.8 &#956;g/mL (65 &#956;M), respectively. Linalool at all concentrations did not affect <i>L. infantum</i> 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.https://www.mdpi.com/1420-3049/24/11/2072insect vectorsneglected tropical diseasesprotozoan parasitessandfliesvisceral leishmaniasis
spellingShingle 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 Sut
In Vitro and In Vivo Effectiveness of Carvacrol, Thymol and Linalool against <i>Leishmania infantum</i>
Molecules
insect vectors
neglected tropical diseases
protozoan parasites
sandflies
visceral leishmaniasis
title In Vitro and In Vivo Effectiveness of Carvacrol, Thymol and Linalool against <i>Leishmania infantum</i>
title_full In Vitro and In Vivo Effectiveness of Carvacrol, Thymol and Linalool against <i>Leishmania infantum</i>
title_fullStr In Vitro and In Vivo Effectiveness of Carvacrol, Thymol and Linalool against <i>Leishmania infantum</i>
title_full_unstemmed In Vitro and In Vivo Effectiveness of Carvacrol, Thymol and Linalool against <i>Leishmania infantum</i>
title_short In Vitro and In Vivo Effectiveness of Carvacrol, Thymol and Linalool against <i>Leishmania infantum</i>
title_sort in vitro and in vivo effectiveness of carvacrol thymol and linalool against i leishmania infantum i
topic insect vectors
neglected tropical diseases
protozoan parasites
sandflies
visceral leishmaniasis
url https://www.mdpi.com/1420-3049/24/11/2072
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