3-methyl-1,2-cyclopentanedione down-regulates age-related NF-kappaB signaling cascade.
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.
Chung
Jae Heun
JH
College of Pharmacy, Pusan National University, Busan 609-735, Korea.
Choi
Seo Young
SY
Kim
Ji Young
JY
Kim
Dae Hyun
DH
Lee
Jae Won
JW
Choi
Jae Sue
JS
Chung
Hae Young
HY
D000375:Aging; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D003069:Coffee / Q000737:chemistry; D003517:Cyclopentanes / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects*; D007249:Inflammation / Q000235:genetics; D008297:Male; D016328:NF-kappa B / Q000235:genetics* / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D015398:Signal Transduction / Q000187:drug effects*
D000893:Anti-Inflammatory Agents; D003069:Coffee; D003517:Cyclopentanes; D016328:NF-kappa B; C471838:3-methyl-1,2-cyclopentanedione