A synthetic hydroxypropenone inhibits nitric oxide, prostaglandin E2, and proinflammatory cytokine synthesis

作者：Liew Choi Yi; Tham Chau Ling; Lam Kok Wai; Mohamad Azam Shah; Kim Min Kyu; Cheah Yoke Kqueen; Zakaria Zainul Amiruddin; Sulaiman Mohd Roslan; Lajis Md Nordin; Israf Daud Ahmad^*

来源：Immunopharmacology and Immunotoxicology, 2010, 32(3): 495-506.

DOI：10.3109/08923970903575708

• COX-2
• cytokines
• hydroxypropenone
• iNOS
• RAW 264.7
• U937

HMP [3-(2-hydroxyphenyl)-1-(5-methyl-furan-2-y-l) propenone] was evaluated for its ability to inhibit the synthesis of major proinflammatory mediators and cytokines in interferon-gamma (IFN-gamma)- and lipopolysaccharide (LPS)-induced RAW 264.7 cells and phorbol myristate acetate (PMA)-differentiated/LPS-induced U937 cells. HMP suppressed the production of nitric oxide (NO) with significant inhibitory effects at doses as low as 0.78 mu M (P < 0.05). Prostaglandin E2 (PGE2) secretion was also inhibited at doses of 12.5 mu M and above (P < 0.01). The secretion of both TNF-alpha and IL-6 were only inhibited at the highest dose used (25 mu M; P < 0.001). IL-1 beta secretion was also inhibited from 12.5 mu M onwards (P < 0.01). This inhibition was demonstrated to be caused by down-regulation of inducible enzymes, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2), without direct effect upon iNOS or COX-2 enzyme activity. HMP only inhibited iNOS (P < 0.001) and IL-1 beta (P < 0.05) gene expression at the highest tested concentration. HMP did not affect the secretion of chemokines IL-8 and monocyte chemotactic protein-1 (MCP-1) and the anti-inflammatory cytokine IL-10. The most striking effect of HMP was its NO inhibitory activity and therefore we conclude that HMP is a selective inhibitor of iNOS.

• 出版日期2010-9