The synthetic curcuminoid BHMC restores endotoxin-stimulated HUVEC dysfunction: specific disruption on enzymatic activity of p38 MAPK
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 survi...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2015
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| Online Access: | http://psasir.upm.edu.my/id/eprint/46706/1/The%20synthetic%20curcuminoid%20BHMC%20restores%20endotoxin-stimulated%20HUVEC%20dysfunction%20specific%20disruption%20on%20enzymatic%20activity%20of%20p38%20MAPK.pdf |
| _version_ | 1825929732644929536 |
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| author | Chau, Ling Tham Harith, Hanis Hazeera Kok, Wai Lam Yi, Joong Chong Cheema, Manraj Singh Sulaiman, Mohd Roslan Lajis, Nordin Ahmad Israf, Daud |
| author_facet | Chau, Ling Tham Harith, Hanis Hazeera Kok, Wai Lam Yi, Joong Chong Cheema, Manraj Singh Sulaiman, Mohd Roslan Lajis, Nordin Ahmad Israf, Daud |
| author_sort | Chau, Ling Tham |
| collection | UPM |
| description | 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. |
| first_indexed | 2024-03-06T09:01:02Z |
| format | Article |
| id | upm.eprints-46706 |
| institution | Universiti Putra Malaysia |
| language | English |
| last_indexed | 2024-03-06T09:01:02Z |
| publishDate | 2015 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | upm.eprints-467062018-02-21T08:15:36Z http://psasir.upm.edu.my/id/eprint/46706/ The synthetic curcuminoid BHMC restores endotoxin-stimulated HUVEC dysfunction: specific disruption on enzymatic activity of p38 MAPK Chau, Ling Tham Harith, Hanis Hazeera Kok, Wai Lam Yi, Joong Chong Cheema, Manraj Singh Sulaiman, Mohd Roslan Lajis, Nordin Ahmad Israf, Daud 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. Elsevier 2015 Article PeerReviewed text en http://psasir.upm.edu.my/id/eprint/46706/1/The%20synthetic%20curcuminoid%20BHMC%20restores%20endotoxin-stimulated%20HUVEC%20dysfunction%20specific%20disruption%20on%20enzymatic%20activity%20of%20p38%20MAPK.pdf Chau, Ling Tham and Harith, Hanis Hazeera and Kok, Wai Lam and Yi, Joong Chong and Cheema, Manraj Singh and Sulaiman, Mohd Roslan and Lajis, Nordin and Ahmad Israf, Daud (2015) The synthetic curcuminoid BHMC restores endotoxin-stimulated HUVEC dysfunction: specific disruption on enzymatic activity of p38 MAPK. European Journal of Pharmacology, 749 (1). pp. 1-11. ISSN 0014-2999; ESSN: 1879-0712 http://www.elsevier.com/locate/issn/00142999 10.1016/j.ejphar.2014.12.015 |
| spellingShingle | Chau, Ling Tham Harith, Hanis Hazeera Kok, Wai Lam Yi, Joong Chong Cheema, Manraj Singh Sulaiman, Mohd Roslan Lajis, Nordin Ahmad Israf, Daud The synthetic curcuminoid BHMC restores endotoxin-stimulated HUVEC dysfunction: specific disruption on enzymatic activity of p38 MAPK |
| title | The synthetic curcuminoid BHMC restores endotoxin-stimulated HUVEC dysfunction: specific disruption on enzymatic activity of p38 MAPK |
| title_full | The synthetic curcuminoid BHMC restores endotoxin-stimulated HUVEC dysfunction: specific disruption on enzymatic activity of p38 MAPK |
| title_fullStr | The synthetic curcuminoid BHMC restores endotoxin-stimulated HUVEC dysfunction: specific disruption on enzymatic activity of p38 MAPK |
| title_full_unstemmed | The synthetic curcuminoid BHMC restores endotoxin-stimulated HUVEC dysfunction: specific disruption on enzymatic activity of p38 MAPK |
| title_short | The synthetic curcuminoid BHMC restores endotoxin-stimulated HUVEC dysfunction: specific disruption on enzymatic activity of p38 MAPK |
| title_sort | synthetic curcuminoid bhmc restores endotoxin stimulated huvec dysfunction specific disruption on enzymatic activity of p38 mapk |
| url | http://psasir.upm.edu.my/id/eprint/46706/1/The%20synthetic%20curcuminoid%20BHMC%20restores%20endotoxin-stimulated%20HUVEC%20dysfunction%20specific%20disruption%20on%20enzymatic%20activity%20of%20p38%20MAPK.pdf |
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