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

1
Faculty of Medicine, Graduate PhD Degree Program in Parasitology, Chiang Mai University, Chiang Mai 50200, Thailand
2
Department of Parasitology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand
3
Faculty of Health and Medicine, Division of Biomedical and Life Sciences, Lancaster University, Lancaster LA1 4YG, UK
4
Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK
5
Department of Parasitology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand
*
Author to whom correspondence should be addressed.
Pathogens 2020, 9(1), 49; https://doi.org/10.3390/pathogens9010049
Received: 9 December 2019 / Revised: 3 January 2020 / Accepted: 7 January 2020 / Published: 9 January 2020
(This article belongs to the Section Human Pathogens)
Leishmania (Mundinia) martiniquensis 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 L. martiniquensis to Amphotericin B deoxycholate (AmB), allicin, and andrographolide was evaluated and the synergistic effects of allicin or andrographolide combined with AmB against L. martiniquensis intracellular amastigotes in mouse peritoneal exudate macrophages (PEMs) were investigated in vitro for the first time. The results showed that L. martiniquensis 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 L. martiniquensis. Four AmB/allicin combinations presented combination index (CI) values less than 1 (0.58–0.68) 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 Leishmania species. View Full-Text
Keywords: Leishmania martiniquensis; Mundinia; Amphotericin B deoxycholate; allicin; andrographolide; synergistic effect; drug combination Leishmania martiniquensis; Mundinia; Amphotericin B deoxycholate; allicin; andrographolide; synergistic effect; drug combination
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MDPI and ACS Style

Intakhan, N.; Chanmol, W.; Somboon, P.; Bates, M.D.; Yardley, V.; Bates, P.A.; Jariyapan, N. Antileishmanial Activity and Synergistic Effects of Amphotericin B Deoxycholate with Allicin and Andrographolide against Leishmania martiniquensis In Vitro. Pathogens 2020, 9, 49.

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