In silico and experimental potentials of 6-shogaol and meglumine antimoniate on Leishmania major: multiple synergistic combinations through modulation of biological properties.
Leishmania major
6-shogaol
Combination therapy
Mechanism of actions
Medicinal plant
Meglumine antimoniate
Journal
Immunologic research
ISSN: 1559-0755
Titre abrégé: Immunol Res
Pays: United States
ID NLM: 8611087
Informations de publication
Date de publication:
18 Aug 2024
18 Aug 2024
Historique:
received:
12
05
2024
accepted:
12
08
2024
medline:
19
8
2024
pubmed:
19
8
2024
entrez:
18
8
2024
Statut:
aheadofprint
Résumé
Conventional therapeutic agents are no longer adequate against leishmaniasis. This complex condition continues to have a high mortality rate and public health impact. The present study aimed to explore an extensive array of experiments to monitor the biological activities of 6-shogaol, a major component of ginger, and meglumine antimoniate (MA or Glucantime®). The binding affinity of 6-shogaol and inducible nitric oxide synthase (iNOS), a major enzyme catalyzing nitric oxide (NO) from L-arginine was the source for the docking outline. The inhibitory effects of 6-shogaol, MA, and mixture were assessed using colorimetric and macrophage assays. Antioxidant activity was inferred by UV-visible spectrophotometry. Variably expressed genes were measured by quantifiable real-time polymerase chain reaction. Apoptotic and cell cycle profiles were analyzed by flow cytometry. Moreover, a DNA fragmentation assay was performed by electrophoresis and antioxidant metabolites include superoxide dismutase (SOD), catalase (CAT), and also nitric oxide (NO) by enzyme-linked immunosorbent assay. 6-shogaol and MA exhibited multiple synergistic mechanisms of action. These included a remarkable leishmanicidal effect, potent antioxidative activity, a high safety index, upregulation of M1 macrophages/Th1-associated cytokines (including, γ-interferon, interleukin-12p40, tumor necrotizing factor-alpha, and associated iNOS), significant cell division capture at the sub-G0/G1 phase, a high profile of apoptosis through DNA fragmentation of the nuclear components. In addition, the activity of NO was substantially elevated by treated intracellular amastigotes, while SOD and CAT activities were significantly diminished. This study is exclusive because no similar investigation has inclusively been conducted before. These comprehensive mechanistic actions form a logical foundation for additional advanced study.
Identifiants
pubmed: 39155331
doi: 10.1007/s12026-024-09530-4
pii: 10.1007/s12026-024-09530-4
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Kerman University of Medical Sciences
ID : 99001204
Informations de copyright
© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
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