Assessment of the antileishmanial activity of diallyl sulfide combined with meglumine antimoniate on Leishmania major: Molecular docking, in vitro, and animal model.

Autor: Zarrinkar F; Leishmaniasis Research Center, Kerman University of Medical Sciences, Kerman, Iran., Sharifi I; Leishmaniasis Research Center, Kerman University of Medical Sciences, Kerman, Iran., Salarkia E; Leishmaniasis Research Center, Kerman University of Medical Sciences, Kerman, Iran., Keyhani A; Leishmaniasis Research Center, Kerman University of Medical Sciences, Kerman, Iran., Babaei Z; Leishmaniasis Research Center, Kerman University of Medical Sciences, Kerman, Iran., Khamesipour A; Center for Research and Training in Skin Diseases and Leprosy, Tehran University of Medical Sciences, Tehran, Iran., Hakimi Parizi M; Leishmaniasis Research Center, Kerman University of Medical Sciences, Kerman, Iran., Molaakbari E; Leishmaniasis Research Center, Kerman University of Medical Sciences, Kerman, Iran., Sharifi F; Research Center of Tropical and Infectious Diseases, Kerman University of Medical Sciences, Kerman, Iran., Dabiri S; Afzalipour School of Medicine and Pathology and Stem Cells Research Center, Kerman University of Medical Sciences, Kerman, Iran., Bamorovat M; Leishmaniasis Research Center, Kerman University of Medical Sciences, Kerman, Iran.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2024 Aug 30; Vol. 19 (8), pp. e0307537. Date of Electronic Publication: 2024 Aug 30 (Print Publication: 2024).
DOI: 10.1371/journal.pone.0307537
Abstrakt: Currently, no safe vaccine against leishmaniasis is available. So far, different control strategies against numerous reservoir hosts and biological vectors have not been environment-friendly and feasible. Hence, employing medicinal components and conventional drugs could be a promising approach to developing novel therapeutic alternatives. This study aimed to explore diallyl sulfide (DAS), a dynamic constituent of garlic, alone and in a mixture with meglumine antimoniate (MAT as standard drug) using in vitro and animal model experiments against Leishmania major stages. The binding affinity of DAS and four major defense elements of the immune system (iNOS, IFN-ɣ, IL-12, and TNF-α) was used to predict the predominant binding mode for molecular docking configurations. Herein, we conducted a broad range of experiments to monitor and assess DAS and MAT potential treatment outcomes. DAS, combined with MAT, displayed no cytotoxicity and employed a powerful anti-leishmanial activity, notably against the clinical stage. The function mechanism involved immunomodulation through the induction of Th1 cytokine phenotypes, triggering a high apoptotic profile, reactive oxygen species (ROS) production, and antioxidant enzymes. This combination significantly decreased cutaneous lesion diameter and parasite load in BALB/c mice. The histopathological findings performed the infiltration of inflammatory cells associated with T-lymphocytes, particularly CD4+ phenotypes, as determined by biochemical markers in alleviating the amastigote stage and improving the pathological changes in L. major infected BALB/c mice. Therefore, DAS and MAT deserve further advanced therapeutic development and should be considered as possible candidates for treating volunteer cases with cutaneous leishmaniasis in designing an upcoming clinical trial.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2024 Zarrinkar et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
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