Zerumbone suppresses the activation of inflammatory mediators in LPS-stimulated U937 macrophages through MyD88-dependent NF-κB/MAPK/PI3K-Akt signaling pathways

Md Areeful Haque, Ibrahim Jantan, Hemavathy Harikrishnan

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Zerumbone (ZER), isolated mainly from the Zingiber zerumbet (Z. zerumbet) rhizomes was found to be effective against numerous inflammatory and immune disorders, however, the molecular and biochemical mechanisms underlying its anti-inflammatory and immunosuppressive properties have not been well studied. This study was carried out to examine the profound effects of ZER on inflammatory mediated MyD88-dependent NF-κB/MAPK/PI3K-Akt signaling pathways in LPS-stimulated U937 human macrophages. ZER significantly suppressed the up-regulation pro-inflammatory mediators, TNF-α IL-1β PGE2, and COX-2 protein in LPS-induced human macrophages. Moreover, ZER significantly downregulated the phosphorylation of NF-κB (p65), IκBα and IKKα/β as well as restored the degradation of IκBα. ZER correspondingly showed remarkable attenuation of the expression of Akt, JNK, ERK, and p38 MAPKs phosphorylation in a concentration-dependent manner. ZER also diminished the expression of upstream signaling molecules TLR4 and MyD88, which are prerequisite for the NF-κB, MAPK and PI3K-Akt activation. Additionally, quantification of relative gene expression of TNF-α IL-1β and COX-2 indicated that, at a higher dose (50 μM), ZER significantly downregulated the elevated mRNA transcription levels of the stated pro-inflammatory markers in LPS-stimulated U937 macrophages. The strong suppressive effects of ZER on the activation of inflammatory markers in the macrophages via MyD88-dependent NF-κB/MAPK/PI3K-Akt signaling pathways suggest that ZER can be a preventive and potent therapeutic candidate for the management of various inflammatory-mediated immune disorders.

Original languageEnglish
Pages (from-to)312-322
Number of pages11
JournalInternational Immunopharmacology
Volume55
DOIs
Publication statusPublished - 1 Feb 2018

Fingerprint

Phosphatidylinositol 3-Kinases
Macrophages
Immune System Diseases
Interleukin-1
Down-Regulation
Phosphorylation
zerumbone
Rhizome
p38 Mitogen-Activated Protein Kinases
Immunosuppressive Agents
Dinoprostone
Anti-Inflammatory Agents
Up-Regulation
Gene Expression
Messenger RNA

Keywords

  • Akt
  • COX-2
  • Inflammation
  • MAPKs
  • NF-κB
  • Zerumbone

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Pharmacology

Cite this

Zerumbone suppresses the activation of inflammatory mediators in LPS-stimulated U937 macrophages through MyD88-dependent NF-κB/MAPK/PI3K-Akt signaling pathways. / Haque, Md Areeful; Jantan, Ibrahim; Harikrishnan, Hemavathy.

In: International Immunopharmacology, Vol. 55, 01.02.2018, p. 312-322.

Research output: Contribution to journalArticle

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