Standardized extract of Zingiber zerumbet suppresses LPS-induced pro-inflammatory responses through NF-κB, MAPK and PI3K-Akt signaling pathways in U937 macrophages.
Anti-Inflammatory Agents, Non-Steroidal
/ chemistry
Biomarkers
/ metabolism
Chromatography, Liquid
Humans
Inflammation
/ drug therapy
Lipopolysaccharides
/ pharmacology
Mitogen-Activated Protein Kinases
/ metabolism
NF-kappa B
/ metabolism
Phosphatidylinositol 3-Kinases
/ metabolism
Plant Extracts
/ chemistry
Proto-Oncogene Proteins c-akt
/ metabolism
Sesquiterpenes
/ analysis
Signal Transduction
/ drug effects
Tandem Mass Spectrometry
U937 Cells
Zingiberaceae
/ chemistry
Anti-inflammatory effects
MAPKs
NF-Κb
PI3K-Akt
Pro-inflammatory cytokines
Zingiber zerumbet
Journal
Phytomedicine : international journal of phytotherapy and phytopharmacology
ISSN: 1618-095X
Titre abrégé: Phytomedicine
Pays: Germany
ID NLM: 9438794
Informations de publication
Date de publication:
15 Feb 2019
15 Feb 2019
Historique:
received:
16
04
2018
revised:
21
06
2018
accepted:
17
09
2018
pubmed:
23
1
2019
medline:
14
6
2019
entrez:
23
1
2019
Statut:
ppublish
Résumé
Zingiber zerumbet rhizome has been used as spices and in traditional medicine to heal various immune-inflammatory related ailments. Although the plant was reported to have potent anti-inflammatory and immunosuppressive properties by several studies, the molecular mechanisms underlying the effects have not been well justified. The study was carried out to investigate the molecular mechanisms underlying the anti-inflammatory properties of the standardized 80% ethanol extract of Z. zerumbet through its effect on mitogen-activated protein kinase (MyD88)-dependent nuclear factor-kappa B (NF-кB), mitogen activated protein kinase (MAPK) and phosphatidylinositol 3-kinase/Akt (PI3K-Akt) signaling pathways in lipopolysaccharide (LPS)-induced U937 human macrophages. Standardization of the 80% ethanol extract of Z. zerumbet was performed by using a validated reversed-phase HPLC method, while LC-MS/MS was used to profile the secondary metabolites. The release of pro-inflammatory markers, tumor necrosis factor (TNF)-α, interleukin (IL)-1β and prostaglandin E The quantitative and qualitative analyses of Z. zerumbet extract showed the presence of several compounds including the major chemical marker zerumbone. Z. zerumbet extract suppressed the release of pro-inflammatory mediators, COX-2 protein expression and downregulated the mRNA expression of pro-inflammatory markers. Z. zerumbet-treatment also blocked NF-κB activation by preventing the phosphorylation of IKKα/β and NF-κB (p65) as well as the phosphorylation and degradation of IκBα. Z. zerumbet extract concentration-dependently inhibited the phosphorylation of respective MAPKs (JNK, ERK, and p38) as well as Akt. Correspondingly, Z. zerumbet extract suppressed the upstream signaling adaptor molecules, TLR4 and MyD88 prerequisite for the NF-κB, MAPKs, and PI3K-Akt activation. The findings suggest that Z. zerumbet has impressive role in suppressing inflammation and related immune disorders by inhibition of various pro-inflammatory markers through the imperative MyD88-dependent NF-κB, MAPKs, and PI3K-Akt activation.
Sections du résumé
BACKGROUND
BACKGROUND
Zingiber zerumbet rhizome has been used as spices and in traditional medicine to heal various immune-inflammatory related ailments. Although the plant was reported to have potent anti-inflammatory and immunosuppressive properties by several studies, the molecular mechanisms underlying the effects have not been well justified.
PURPOSE
OBJECTIVE
The study was carried out to investigate the molecular mechanisms underlying the anti-inflammatory properties of the standardized 80% ethanol extract of Z. zerumbet through its effect on mitogen-activated protein kinase (MyD88)-dependent nuclear factor-kappa B (NF-кB), mitogen activated protein kinase (MAPK) and phosphatidylinositol 3-kinase/Akt (PI3K-Akt) signaling pathways in lipopolysaccharide (LPS)-induced U937 human macrophages.
METHODS
METHODS
Standardization of the 80% ethanol extract of Z. zerumbet was performed by using a validated reversed-phase HPLC method, while LC-MS/MS was used to profile the secondary metabolites. The release of pro-inflammatory markers, tumor necrosis factor (TNF)-α, interleukin (IL)-1β and prostaglandin E
RESULTS
RESULTS
The quantitative and qualitative analyses of Z. zerumbet extract showed the presence of several compounds including the major chemical marker zerumbone. Z. zerumbet extract suppressed the release of pro-inflammatory mediators, COX-2 protein expression and downregulated the mRNA expression of pro-inflammatory markers. Z. zerumbet-treatment also blocked NF-κB activation by preventing the phosphorylation of IKKα/β and NF-κB (p65) as well as the phosphorylation and degradation of IκBα. Z. zerumbet extract concentration-dependently inhibited the phosphorylation of respective MAPKs (JNK, ERK, and p38) as well as Akt. Correspondingly, Z. zerumbet extract suppressed the upstream signaling adaptor molecules, TLR4 and MyD88 prerequisite for the NF-κB, MAPKs, and PI3K-Akt activation.
CONCLUSION
CONCLUSIONS
The findings suggest that Z. zerumbet has impressive role in suppressing inflammation and related immune disorders by inhibition of various pro-inflammatory markers through the imperative MyD88-dependent NF-κB, MAPKs, and PI3K-Akt activation.
Identifiants
pubmed: 30668369
pii: S0944-7113(18)30466-5
doi: 10.1016/j.phymed.2018.09.183
pii:
doi:
Substances chimiques
Anti-Inflammatory Agents, Non-Steroidal
0
Biomarkers
0
Lipopolysaccharides
0
NF-kappa B
0
Plant Extracts
0
Sesquiterpenes
0
zerumbone
471-05-6
Phosphatidylinositol 3-Kinases
EC 2.7.1.-
Proto-Oncogene Proteins c-akt
EC 2.7.11.1
Mitogen-Activated Protein Kinases
EC 2.7.11.24
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
195-205Informations de copyright
Copyright © 2018 Elsevier GmbH. All rights reserved.