Lupeol and amphotericin B mediate synergistic anti-leishmanial immunomodulatory effects in Leishmania donovani-infected BALB/c mice.
Amphotericin B
/ pharmacology
Animals
Antiprotozoal Agents
/ pharmacology
Cells, Cultured
Cytokines
/ genetics
Drug Synergism
Gene Expression
/ drug effects
Immunoblotting
Immunomodulation
/ drug effects
Leishmania donovani
/ drug effects
Leishmaniasis, Visceral
/ drug therapy
Mice, Inbred BALB C
Nitrites
/ immunology
Pentacyclic Triterpenes
/ pharmacology
Reverse Transcriptase Polymerase Chain Reaction
Spleen
/ drug effects
Amphotericin B
Inflammatory cytokine
Leishmania donovani
Lupeol
p38 MAPK
Journal
Cytokine
ISSN: 1096-0023
Titre abrégé: Cytokine
Pays: England
ID NLM: 9005353
Informations de publication
Date de publication:
01 2021
01 2021
Historique:
received:
29
04
2020
accepted:
22
09
2020
pubmed:
2
10
2020
medline:
28
12
2021
entrez:
1
10
2020
Statut:
ppublish
Résumé
Leishmania donovani, a protozoan parasite, inflicts the disease Visceral leishmaniasis (VL) Worldwide. The only orally bioavailable drug miltefosine is toxic, whereas liposomal amphotericin B (AmpB) is expensive. Lupeol, a triterpenoid from Sterculia villosa bark, was exhibited immunomodulatory and anti-leishmanial activity in experimental VL. Herein, we evaluated synergism between sub-optimum dose of AmpB and lupeol in anti-leishmanial and immunomodulatory effects in L. donovani-infected BALB/c mice. We observed that a combination of sub-optimum dose of lupeol and AmpB significantly reduced the hepatic and splenic parasitic burden accompanied by enhanced nitric oxide production, robust induction of Th1 cytokines (IL-12 and IFN-γ) but suppressed Th2 cytokine (IL-10 and TGF- β) production. The treatment with the lupeol-AmpB combination enhanced p38mitogen-activated protein kinase (p38MAPK), but reduced extracellular signal-related kinase (ERK-1/2), phosphorylation and up-regulated pro-inflammatory response. The present work thus indicates a lupeol-AmpB-mediated immunotherapeutic approach for eliminating the parasite-induced immunosuppression.
Identifiants
pubmed: 33002744
pii: S1043-4666(20)30335-5
doi: 10.1016/j.cyto.2020.155319
pii:
doi:
Substances chimiques
Antiprotozoal Agents
0
Cytokines
0
Nitrites
0
Pentacyclic Triterpenes
0
Amphotericin B
7XU7A7DROE
lupeol
O268W13H3O
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
155319Informations de copyright
Copyright © 2020 Elsevier Ltd. All rights reserved.