A synthetic curcuminoid derivative inhibits nitric oxide and proinflammatory cytokine synthesis

Chau Ling Tham, Choi Yi Liew, Kok Wai Lam, Azam Shah Mohamad, Min Kyu Kim, Yoke Kqueen Cheah, Zainul Amirudin Zakaria, Mohd Roslan Sulaiman, Nordin H. Lajis, Daud A. Israf

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

Curcumin is a highly pleiotropic molecule with significant regulatory effects upon inflammation and inflammatory related diseases. However curcumin has one major important limitation in which it has poor bioavailability. Design of synthetic structural derivatives of curcumin is but one approach that has been used to overcome its poor bioavailability while retaining, or further enhancing, its drug-like effects. We have synthesized a series of curcumin analogues and describe the effects of 2,6-bis-4-(hydroxyl-3-methoxy-benzylidine)-cyclohexanone or BHMC upon nitric oxide and cytokine synthesis in cellular models of inflammation. BHMC showed a significant dose-response inhibitory action upon the synthesis of NO and we have shown that this effect was due to suppression of both iNOS gene and enzyme expression without any effects upon scavenging of nitrite. We also demonstrated that BHMC has a very minimal effect upon iNOS activity with no effect at all upon the secretion of PGE2 but has a strong inhibitory effect upon MCP-1 and IL-10 secretion and gene expression. Secretion and gene expression of TNF-α and IL-6 were moderately inhibited whereas IL-8 and IL-1β were not altered. We conclude that BHMC selectively inhibits the synthesis of several inflammatory mediators. BHMC should be considered a promising drug lead for preclinical and further pharmacological studies.

Original languageEnglish
Pages (from-to)247-254
Number of pages8
JournalEuropean Journal of Pharmacology
Volume628
Issue number1-3
DOIs
Publication statusPublished - 25 Feb 2010
Externally publishedYes

Fingerprint

Curcumin
Nitric Oxide
Cytokines
Gene Expression
Biological Availability
Inflammation
Nitrites
Interleukin-8
Interleukin-1
Dinoprostone
Pharmaceutical Preparations
Hydroxyl Radical
Interleukin-10
Interleukin-6
Pharmacology
Enzymes

Keywords

  • Chemokine
  • Curcuminoid
  • Cytokine
  • iNOS
  • Macrophage

ASJC Scopus subject areas

  • Pharmacology

Cite this

A synthetic curcuminoid derivative inhibits nitric oxide and proinflammatory cytokine synthesis. / Tham, Chau Ling; Liew, Choi Yi; Lam, Kok Wai; Mohamad, Azam Shah; Kim, Min Kyu; Cheah, Yoke Kqueen; Zakaria, Zainul Amirudin; Sulaiman, Mohd Roslan; Lajis, Nordin H.; Israf, Daud A.

In: European Journal of Pharmacology, Vol. 628, No. 1-3, 25.02.2010, p. 247-254.

Research output: Contribution to journalArticle

Tham, CL, Liew, CY, Lam, KW, Mohamad, AS, Kim, MK, Cheah, YK, Zakaria, ZA, Sulaiman, MR, Lajis, NH & Israf, DA 2010, 'A synthetic curcuminoid derivative inhibits nitric oxide and proinflammatory cytokine synthesis', European Journal of Pharmacology, vol. 628, no. 1-3, pp. 247-254. https://doi.org/10.1016/j.ejphar.2009.11.053
Tham, Chau Ling ; Liew, Choi Yi ; Lam, Kok Wai ; Mohamad, Azam Shah ; Kim, Min Kyu ; Cheah, Yoke Kqueen ; Zakaria, Zainul Amirudin ; Sulaiman, Mohd Roslan ; Lajis, Nordin H. ; Israf, Daud A. / A synthetic curcuminoid derivative inhibits nitric oxide and proinflammatory cytokine synthesis. In: European Journal of Pharmacology. 2010 ; Vol. 628, No. 1-3. pp. 247-254.
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