Antileishmanial Activity and Synergistic Effects of Amphotericin B Deoxycholate with Allicin and Andrographolide against <i>Leishmania martiniquensis</i> In Vitro

<i>Leishmania</i> (<i>Mundinia</i>) <i>martiniquensis</i> is a causative agent of visceral leishmaniasis, but in HIV-infected patients both visceral and disseminated cutaneous leishmaniasis are presented. Recurrence of the disease after treatment has been reported...

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Main Authors: Nuchpicha Intakhan, Wetpisit Chanmol, Pradya Somboon, Michelle D. Bates, Vanessa Yardley, Paul A. Bates, Narissara Jariyapan
Format: Article
Language:English
Published: MDPI AG 2020-01-01
Series:Pathogens
Subjects:
Online Access:https://www.mdpi.com/2076-0817/9/1/49
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author Nuchpicha Intakhan
Wetpisit Chanmol
Pradya Somboon
Michelle D. Bates
Vanessa Yardley
Paul A. Bates
Narissara Jariyapan
author_facet Nuchpicha Intakhan
Wetpisit Chanmol
Pradya Somboon
Michelle D. Bates
Vanessa Yardley
Paul A. Bates
Narissara Jariyapan
author_sort Nuchpicha Intakhan
collection DOAJ
description <i>Leishmania</i> (<i>Mundinia</i>) <i>martiniquensis</i> is a causative agent of visceral leishmaniasis, but in HIV-infected patients both visceral and disseminated cutaneous leishmaniasis are presented. Recurrence of the disease after treatment has been reported in some cases indicating that improved chemotherapy is required. In this study, the susceptibility of <i>L. martiniquensis</i> to Amphotericin B deoxycholate (AmB), allicin, and andrographolide was evaluated and the synergistic effects of allicin or andrographolide combined with AmB against <i>L. martiniquensis</i> intracellular amastigotes in mouse peritoneal exudate macrophages (PEMs) were investigated in vitro for the first time. The results showed that <i>L. martiniquensis</i> was highly susceptible to AmB as expected, but allicin and andrographolide had selectivity index (SI) values greater than 10, indicating promise in both compounds for treatment of host cells infected with <i>L. martiniquensis</i>. Four AmB/allicin combinations presented combination index (CI) values less than 1 (0.58&#8722;0.68) for intracellular amastigotes indicating synergistic effects. The combination with the highest dose reduction index (DRI) allowed an approximately four-fold reduction of AmB use in that combination. No synergistic effects were observed in AmB/andrographolide combinations. The data provided in this study leads for further study to develop novel therapeutic agents and improve the treatment outcome for leishmaniasis caused by this <i>Leishmania</i> species.
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spelling doaj.art-9ddd8fa9a05a4d1facc85677c2141e5e2022-12-22T02:53:24ZengMDPI AGPathogens2076-08172020-01-01914910.3390/pathogens9010049pathogens9010049Antileishmanial Activity and Synergistic Effects of Amphotericin B Deoxycholate with Allicin and Andrographolide against <i>Leishmania martiniquensis</i> In VitroNuchpicha Intakhan0Wetpisit Chanmol1Pradya Somboon2Michelle D. Bates3Vanessa Yardley4Paul A. Bates5Narissara Jariyapan6Faculty of Medicine, Graduate PhD Degree Program in Parasitology, Chiang Mai University, Chiang Mai 50200, ThailandDepartment of Parasitology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, ThailandDepartment of Parasitology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, ThailandFaculty of Health and Medicine, Division of Biomedical and Life Sciences, Lancaster University, Lancaster LA1 4YG, UKFaculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UKFaculty of Health and Medicine, Division of Biomedical and Life Sciences, Lancaster University, Lancaster LA1 4YG, UKDepartment of Parasitology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand<i>Leishmania</i> (<i>Mundinia</i>) <i>martiniquensis</i> is a causative agent of visceral leishmaniasis, but in HIV-infected patients both visceral and disseminated cutaneous leishmaniasis are presented. Recurrence of the disease after treatment has been reported in some cases indicating that improved chemotherapy is required. In this study, the susceptibility of <i>L. martiniquensis</i> to Amphotericin B deoxycholate (AmB), allicin, and andrographolide was evaluated and the synergistic effects of allicin or andrographolide combined with AmB against <i>L. martiniquensis</i> intracellular amastigotes in mouse peritoneal exudate macrophages (PEMs) were investigated in vitro for the first time. The results showed that <i>L. martiniquensis</i> was highly susceptible to AmB as expected, but allicin and andrographolide had selectivity index (SI) values greater than 10, indicating promise in both compounds for treatment of host cells infected with <i>L. martiniquensis</i>. Four AmB/allicin combinations presented combination index (CI) values less than 1 (0.58&#8722;0.68) for intracellular amastigotes indicating synergistic effects. The combination with the highest dose reduction index (DRI) allowed an approximately four-fold reduction of AmB use in that combination. No synergistic effects were observed in AmB/andrographolide combinations. The data provided in this study leads for further study to develop novel therapeutic agents and improve the treatment outcome for leishmaniasis caused by this <i>Leishmania</i> species.https://www.mdpi.com/2076-0817/9/1/49<i>leishmania</i> <i>martiniquensis</i><i>mundinia</i>amphotericin b deoxycholateallicinandrographolidesynergistic effectdrug combination
spellingShingle Nuchpicha Intakhan
Wetpisit Chanmol
Pradya Somboon
Michelle D. Bates
Vanessa Yardley
Paul A. Bates
Narissara Jariyapan
Antileishmanial Activity and Synergistic Effects of Amphotericin B Deoxycholate with Allicin and Andrographolide against <i>Leishmania martiniquensis</i> In Vitro
Pathogens
<i>leishmania</i> <i>martiniquensis</i>
<i>mundinia</i>
amphotericin b deoxycholate
allicin
andrographolide
synergistic effect
drug combination
title Antileishmanial Activity and Synergistic Effects of Amphotericin B Deoxycholate with Allicin and Andrographolide against <i>Leishmania martiniquensis</i> In Vitro
title_full Antileishmanial Activity and Synergistic Effects of Amphotericin B Deoxycholate with Allicin and Andrographolide against <i>Leishmania martiniquensis</i> In Vitro
title_fullStr Antileishmanial Activity and Synergistic Effects of Amphotericin B Deoxycholate with Allicin and Andrographolide against <i>Leishmania martiniquensis</i> In Vitro
title_full_unstemmed Antileishmanial Activity and Synergistic Effects of Amphotericin B Deoxycholate with Allicin and Andrographolide against <i>Leishmania martiniquensis</i> In Vitro
title_short Antileishmanial Activity and Synergistic Effects of Amphotericin B Deoxycholate with Allicin and Andrographolide against <i>Leishmania martiniquensis</i> In Vitro
title_sort antileishmanial activity and synergistic effects of amphotericin b deoxycholate with allicin and andrographolide against i leishmania martiniquensis i in vitro
topic <i>leishmania</i> <i>martiniquensis</i>
<i>mundinia</i>
amphotericin b deoxycholate
allicin
andrographolide
synergistic effect
drug combination
url https://www.mdpi.com/2076-0817/9/1/49
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