Abstract
A significant barrier to optimal antileishmanial treatment is low efficacy and the emergence of drug resistance. Multiple approaches were used to monitor and assess crocin (a central component of saffron) mixed with amphotericin B (AmpB) potential in silico and in vitro consequences. The binding behavior of crocin and iNOS was the purpose of molecular docking. The results showed that crocin coupled with AmpB demonstrated a safe combination, extremely antileishmanial, suppressed Leishmania arginase absorption, and increased parasite death. This natural flower component is a robust antioxidant, significantly promoting the expression of the Th1-connected cytokines (IL12p40, IFN-γ, and TNF- α), iNOS, and transcription factors (Elk-1, c-Fos, and STAT-1). In comparison, the expression of the Th2-associated phenotypes (IL-10, IL-4, and TGF-β) was significantly reduced. The leishmanicidal effect of this combination was also mediated through programmed cell death (PCD), as confirmed by the manifestation of phosphatidylserine and cell cycle detention at the sub-GO/G1 phase. In conclusion, crocin with AmpB synergistically exerted in vitro antileishmanial action, generated nitric oxide and reactive oxygen species, modulated Th1, and Th2 phenotypes and transfer factors, enhanced PCD profile and arrested the cell cycle of Leishmania major promastigotes. The main action of crocin and AmpB involved wide-ranging mechanistic insights for conducting other clinical settings as promising drug candidates for cutaneous leishmaniasis. Therefore, this combination could be esteemed as a basis for a potential bioactive component and a logical source for leishmanicidal drug development against CL in future advanced clinical settings.
Funder
Vice-Chancellor for Research and Technology, Kerman University of Medical Sciences, Kerman, Iran
Publisher
Public Library of Science (PLoS)
Reference72 articles.
1. From infection to vaccination: reviewing the global burden, history of vaccine development, and recurring challenges in global leishmaniasis protection;G Volpedo;Expert Rev Vaccines,2021
2. A spatio-temporal agent-based approach for modeling the spread of zoonotic cutaneous leishmaniasis in northeast Iran;M Tabasi;Parasit Vectors,2020
3. WHO. Leishmaniasis. In: World Health Organization [Internet]. 2022. https://www.who.int/leishmaniasis/en/
4. Leishmaniasis: a review;E Torres-Guerrero;F1000Research,2017
5. Global leishmaniasis surveillance: 2019–2020, a baseline for the 2030 roadmap/Surveillance mondiale de la leishmaniose: 2019–2020, une periode de reference pour la feuille de route a l’horizon 2030;JA Ruiz-Postigo;Wkly Epidemiol Rec,2021