The synthetic curcuminoid BHMC restores endotoxin-stimulated HUVEC dysfunction: Specific disruption on enzymatic activity of p38 MAPK

Chau Ling Tham, Hanis Hazeera Harith, Kok Wai Lam, Yi Joong Chong, Manraj Singh Cheema, Mohd Roslan Sulaiman, Nordin Hj Lajis, Daud Ahmad Israf

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

2,6-bis-(4-hydroxyl-3-methoxybenzylidine)cyclohexanone (BHMC) has been proven to selectively inhibit the synthesis of proinflammatory mediators in lipopolysaccharide-induced U937 monocytes through specific interruption of p38 Mitogen-Activated Protein Kinase enzymatic activity and improves the survival rate in a murine lethal sepsis model. The present study addressed the effects of BHMC upon lipopolysaccharide-induced endothelial dysfunction in human umbilical vein endothelial cells to determine the underlying mechanisms. The cytotoxicity effect of BHMC on HUVEC were determined by MTT assay. The effects of BHMC on endothelial dysfunction induced by lipopolysaccharide such as endothelial hyperpermeability, monocyte-endothelial adhesion, transendothelial migration, up-regulation of adhesion molecules and chemokines were evaluated. The effects of BHMC at transcriptional and post-translational levels were determined by Reverse Transcriptase-Polymerase Chain Reaction and Western Blots. The mode of action of BHMC was dissected by looking into the activation of Nuclear Factor-kappa B and Mitogen-Activated Protein Kinases. BHMC concentration-dependently reduced endothelial hyperpermeability, leukocyte-endothelial cell adhesion and monocyte transendothelial migration through inhibition of the protein expression of adhesion molecules (Intercellular Adhesion Molecule-1 and Vascular Cell Adhesion Molecule-1) and secretion of chemokines (Monocyte Chemotactic Protein-1) at the transcriptional level. BHMC restored endothelial dysfunction via selective inhibition of p38 Mitogen-Activated Protein Kinase enzymatic activity which indirectly prevents the activation of Nuclear Factor-kappaB and Activator Protein-1 transcription factors. These findings further support earlier observations on the inhibition of BHMC on inflammatory events through specific disruption of p38 Mitogen-Activated Protein Kinase enzymatic activity and provide new insights into the inhibitory effects of BHMC on lipopolysaccharide-induced endothelial dysfunction.

Original languageEnglish
Pages (from-to)1-11
Number of pages11
JournalEuropean Journal of Pharmacology
Volume749
DOIs
Publication statusPublished - 15 Feb 2015

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p38 Mitogen-Activated Protein Kinases
Endotoxins
Hydroxyl Radical
Lipopolysaccharides
Transendothelial and Transepithelial Migration
Monocytes
Chemokines
cyclohexanone
Vascular Cell Adhesion Molecule-1
NF-kappa B
Chemokine CCL2
Human Umbilical Vein Endothelial Cells
Transcription Factor AP-1
Intercellular Adhesion Molecule-1
Mitogen-Activated Protein Kinases
Reverse Transcriptase Polymerase Chain Reaction
Cell Adhesion
Sepsis
Leukocytes
Transcription Factors

Keywords

  • BHMC
  • Curcumin
  • HUVECs
  • Monocytes
  • NF-κ-Absp
  • p38 MAPK

ASJC Scopus subject areas

  • Pharmacology

Cite this

The synthetic curcuminoid BHMC restores endotoxin-stimulated HUVEC dysfunction : Specific disruption on enzymatic activity of p38 MAPK. / Tham, Chau Ling; Hazeera Harith, Hanis; Lam, Kok Wai; Joong Chong, Yi; Singh Cheema, Manraj; Roslan Sulaiman, Mohd; Hj Lajis, Nordin; Ahmad Israf, Daud.

In: European Journal of Pharmacology, Vol. 749, 15.02.2015, p. 1-11.

Research output: Contribution to journalArticle

Tham, Chau Ling ; Hazeera Harith, Hanis ; Lam, Kok Wai ; Joong Chong, Yi ; Singh Cheema, Manraj ; Roslan Sulaiman, Mohd ; Hj Lajis, Nordin ; Ahmad Israf, Daud. / The synthetic curcuminoid BHMC restores endotoxin-stimulated HUVEC dysfunction : Specific disruption on enzymatic activity of p38 MAPK. In: European Journal of Pharmacology. 2015 ; Vol. 749. pp. 1-11.
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AU - Singh Cheema, Manraj

AU - Roslan Sulaiman, Mohd

AU - Hj Lajis, Nordin

AU - Ahmad Israf, Daud

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