3-Methyl-1,2-cyclopentanedione Down-Regulates Age-Related NF-(kappa)B Signaling Cascade
2007
Chung, J.H. | Choi, S.Y. | Kim, J.Y. | Kim, D.H. | Lee, J.W. | Choi, J.S. | Chung, H.Y.
Activation of the redox-sensitive transcription factor, nuclear factor-kappa B (NF-(kappa)B), plays a central role in inflammation and aging processes by inducing pro-inflammatory genes. The present study was designed to unravel the molecular mechanisms underlying the anti-inflammation effects of 3-methyl-1,2-cyclopentanedione (3-MCP) in coffee extracts. In particular, we investigated the effects of 3-MCP on the modulation of NF-(kappa)B signaling pathways and its target genes in the kidneys of aged animal rats: young (6 months old), old (21 months old), and old 3-MCP-fed (4 and 8 mg/kg/day for 10 days). The results strongly show that 3-MCP exerted potent anti-inflammatory effects, significantly reducing (i) the phosphorylation of inhibitor (kappa)B (I kappa B) and other NF-(kappa)B upstream events; (ii) the translocation of NF-(kappa)B into the nucleus; (iii) the expression of iNOS and COX-2; and (iv) pro-inflammatory genes such as VCAM-1, MCP-1, and IL-6. Furthermore, 3-MCP suppressed reactive oxygen species levels. Taken together, our results clearly demonstrate that 3-MCP modulated the age-related NF-(kappa)B signaling cascade and its pro-inflammatory genes. Therefore, 3-MCP is proposed to be an effective anti-inflammatory agent that can be a novel approach for the therapy of inflammation.
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