In vitro and in vivo therapeutic potentials of 6-gingerol in combination with amphotericin B for treatment of Leishmania major infection: Powerful synergistic and multifunctional effects.
Amphotericin B
/ therapeutic use
Animals
Apoptosis
Catechols
/ therapeutic use
Cell Line
Cytokines
/ metabolism
Drug Synergism
Drug Therapy, Combination
Fatty Alcohols
/ therapeutic use
Zingiber officinale
Leishmania major
/ physiology
Leishmaniasis, Cutaneous
/ drug therapy
Macrophages
/ immunology
Mice
Mice, Inbred BALB C
STAT1 Transcription Factor
/ genetics
Th1 Cells
/ immunology
Th1-Th2 Balance
6-Gingerol
Amphotericin B
Combination therapy
Leishmania major
Pathological profiles
Journal
International immunopharmacology
ISSN: 1878-1705
Titre abrégé: Int Immunopharmacol
Pays: Netherlands
ID NLM: 100965259
Informations de publication
Date de publication:
Dec 2021
Dec 2021
Historique:
received:
19
07
2021
revised:
11
10
2021
accepted:
12
10
2021
pubmed:
24
10
2021
medline:
25
3
2022
entrez:
23
10
2021
Statut:
ppublish
Résumé
The ongoing conventional drugs for leishmaniasis treatment are insufficient. The present study aimed to assess 6-gingerol alone and in combination with amphotericin B on Leishmania major stages using experimental and in vivo murine models. Here, arrays of experimental approaches were designed to monitor and evaluate the 6-gingerol potential therapeutic outcomes. The binding affinity of 6-gingerol and IFN-γ was the basis for docking conformations. 6-Gingerol combined with amphotericin B represented a safe mixture, extremely leishmanicidal, a potent antioxidant, induced a remarkable apoptotic index, significantly increased the expression of the Th1-related cytokines (IL-12p40, IFN-γ, and TNF- α), iNOS, and transcription factors (STAT1, c-Fos, and Elk-1). In contrast, the expression of the Th2-related cytokines was significantly downregulated (p < 0.001). This combination was also potent when the lesion appearance was evaluated following three weeks of treatment. The histopathological and immunohistochemical patterns of the murine model represented clusters of CD4
Identifiants
pubmed: 34688150
pii: S1567-5769(21)00910-3
doi: 10.1016/j.intimp.2021.108274
pii:
doi:
Substances chimiques
Catechols
0
Cytokines
0
Fatty Alcohols
0
STAT1 Transcription Factor
0
Amphotericin B
7XU7A7DROE
gingerol
925QK2Z900
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
108274Informations de copyright
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