PMID- 20338073
OWN - NLM
STAT- MEDLINE
DCOM- 20100903
LR  - 20220408
IS  - 1475-2662 (Electronic)
IS  - 0007-1145 (Linking)
VI  - 104
IP  - 4
DP  - 2010 Aug
TI  - NF-kappaB-dependent anti-inflammatory activity of urolithins, gut microbiota 
      ellagic acid-derived metabolites, in human colonic fibroblasts.
PG  - 503-12
LID - 10.1017/S0007114510000826 [doi]
AB  - Previous studies have reported the anti-inflammatory properties of pomegranate 
      extracts, suggesting that ellagitannins (ET) and ellagic acid (EA) are the main 
      anti-inflammatory compounds. However, both ET and EA are metabolised in vivo by 
      the gut microbiota to yield urolithins (Uro) which can be found in the gut and in 
      systemic bloodstream. The present study was carried out to evaluate the 
      individual effect of EA and their microbiota-derived metabolites Uro on colon 
      fibroblasts upon IL-1beta treatment as an in vitro inflammation model. Uro-A and 
      Uro-B (10 microm) inhibited PGE2 production (85 and 40 %, respectively) after 
      IL-1beta stimulation, whereas EA did not show any effect. Uro-A, but not Uro-B, 
      down-regulated cyclo-oxygenase-2 (COX-2) and microsomal PGE synthase-1 (mPGES-1) 
      mRNA expression and protein levels. Both Uro inhibited NF-kappaB translocation to 
      nucleus. Slight but significant effects were found in the activation of 
      mitogen-activated protein kinase (MAPK) pathways. Uro-A lowered c-Jun N-terminal 
      kinase phosphorylation state, and both Uro inhibited p38 activation. No 
      metabolites derived from Uro or EA were found in the cell media upon incubation 
      of EA or Uro with the cells, and only traces of the compounds were found inside 
      the cells. The present results suggest that Uro, mainly Uro-A, are the main 
      compounds that are responsible for the pomegranate anti-inflammatory properties. 
      The mechanism of action implicated seems to be via the inhibition of activation 
      of NF-kappaB and MAPK, down-regulation of COX-2 and mPGES-1 expressions, and 
      consequently,via the reduction of PGE2 production. Taking into account that Uro 
      did not enter the cells, a competitive binding for IL-1beta membrane receptor 
      cannot be discarded.
FAU - Gonzalez-Sarrias, Antonio
AU  - Gonzalez-Sarrias A
AD  - Department of Food Science and Technology, Research Group on Quality, Safety and 
      Bioactivity of Plant Foods, CEBAS-CSIC, 30100 Campus de Espinardo, Murcia, Spain.
FAU - Larrosa, Mar
AU  - Larrosa M
FAU - Tomas-Barberan, Francisco Abraham
AU  - Tomas-Barberan FA
FAU - Dolara, Piero
AU  - Dolara P
FAU - Espin, Juan Carlos
AU  - Espin JC
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100326
PL  - England
TA  - Br J Nutr
JT  - The British journal of nutrition
JID - 0372547
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Coumarins)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Interleukin-1beta)
RN  - 0 (NF-kappa B)
RN  - 0 (Plant Extracts)
RN  - 0 (RNA, Messenger)
RN  - 19YRN3ZS9P (Ellagic Acid)
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 5.3.- (Intramolecular Oxidoreductases)
RN  - EC 5.3.99.3 (PTGES protein, human)
RN  - EC 5.3.99.3 (Prostaglandin-E Synthases)
RN  - K7Q1JQR04M (Dinoprostone)
SB  - IM
MH  - Anti-Inflammatory Agents/metabolism/*pharmacology
MH  - Colon/*drug effects/metabolism/microbiology
MH  - Coumarins/metabolism/*pharmacology
MH  - Cyclooxygenase 2/genetics/metabolism
MH  - Dinoprostone/metabolism
MH  - Down-Regulation
MH  - Ellagic Acid/metabolism/*pharmacology
MH  - Fibroblasts/*drug effects/metabolism
MH  - Humans
MH  - Inflammation/chemically induced/drug therapy
MH  - Inflammation Mediators/metabolism
MH  - Interleukin-1beta
MH  - Intramolecular Oxidoreductases/genetics/metabolism
MH  - Lythraceae/chemistry
MH  - Mitogen-Activated Protein Kinases/metabolism
MH  - NF-kappa B/*metabolism
MH  - Plant Extracts/*pharmacology
MH  - Prostaglandin-E Synthases
MH  - RNA, Messenger/metabolism
EDAT- 2010/03/27 06:00
MHDA- 2010/09/04 06:00
CRDT- 2010/03/27 06:00
PHST- 2010/03/27 06:00 [entrez]
PHST- 2010/03/27 06:00 [pubmed]
PHST- 2010/09/04 06:00 [medline]
AID - S0007114510000826 [pii]
AID - 10.1017/S0007114510000826 [doi]
PST - ppublish
SO  - Br J Nutr. 2010 Aug;104(4):503-12. doi: 10.1017/S0007114510000826. Epub 2010 Mar 
      26.