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3-methyl-1,2-cyclopentanedione down-regulates age-related NF-kappaB signaling cascade.

Abstract
Activation of the redox-sensitive transcription factor, nuclear factor-kappa B (NF-kappaB), 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-kappaB 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 kappaB (IkappaB) and other NF-kappaB upstream events; (ii) the translocation of NF-kappaB 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-kappaB 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.
AuthorsJae Heun Chung, Seo Young Choi, Ji Young Kim, Dae Hyun Kim, Jae Won Lee, Jae Sue Choi, Hae Young Chung
JournalJournal of agricultural and food chemistry (J Agric Food Chem) Vol. 55 Issue 16 Pg. 6787-92 (Aug 08 2007) ISSN: 0021-8561 [Print] United States
PMID17629301 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Anti-Inflammatory Agents
  • Coffee
  • Cyclopentanes
  • NF-kappa B
  • 3-methyl-1,2-cyclopentanedione
Topics
  • Aging
  • Animals
  • Anti-Inflammatory Agents (pharmacology)
  • Coffee (chemistry)
  • Cyclopentanes (pharmacology)
  • Down-Regulation (drug effects)
  • Inflammation (genetics)
  • Male
  • NF-kappa B (genetics, metabolism)
  • Rats
  • Rats, Inbred F344
  • Signal Transduction (drug effects)

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