PMID- 32306507
OWN - NLM
STAT- MEDLINE
DCOM- 20210715
LR  - 20221005
IS  - 1613-4133 (Electronic)
IS  - 1613-4125 (Print)
IS  - 1613-4125 (Linking)
VI  - 64
IP  - 11
DP  - 2020 Jun
TI  - Inhibition of 5-Lipoxygenase-Derived Leukotrienes and Hemiketals as a Novel 
      Anti-Inflammatory Mechanism of Urolithins.
PG  - e2000129
LID - 10.1002/mnfr.202000129 [doi]
AB  - SCOPE: Urolithins (Uro), gut microbial metabolites derived from ellagic acid 
      (EA), reach significant concentrations in the human colon. Uro-A exerts 
      anti-inflammatory activity in animal models of inflammatory bowel diseases 
      (IBDs). It is hypothesized that Uro can modulate the biosynthesis of 
      leukocyte-derived inflammatory eicosanoids from the 5-lipoxygenase (5-LOX), 
      cyclooxygenase-2 (COX-2), and 5-LOX/COX-2 pathways, relevant in the onset and 
      progression of IBDs, including 5-hydroxyeicosatetraenoic acids (5-HETEs), 
      leukotriene-B(4) (LTB(4) ), prostaglandin E(2) (PGE(2) ), and hemiketals (HKE(2) 
      and HKD(2) ). METHODS AND RESULTS: Leukocytes, obtained from six healthy donors, 
      are stimulated with lipopolysaccharide and calcium ionophore A23187. Uro, at 
      concentrations found in the human colon (1-15 microm), decrease eicosanoid 
      biosynthesis and COX-2 levels in the activated leukocytes. In contrast, EA and 
      conjugated Uro (glucuronides and sulfates) are inactive. Uro-A and isourolithin-A 
      reduce the formation of the 5-LOX/COX-2 products HKE(2) and HKD(2) through the 
      COX-2 pathway (down-regulation of COX-2 and PGE2), whereas Uro-C reduces 5-HETE 
      and LTB(4) via inhibition of 5-LOX. CONCLUSIONS: The results show that 
      physiologically relevant colonic Uro target eicosanoid biosynthetic pathways. The 
      effect on HKs and LTB(4) formation is unprecedented and expands the knowledge on 
      anti-inflammatory mechanisms of Uro against IBDs.
CI  - (c) 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
FAU - Gimenez-Bastida, Juan Antonio
AU  - Gimenez-Bastida JA
AUID- ORCID: 0000-0002-1244-8764
AD  - Department of Pharmacology and Vanderbilt Institute of Chemical Biology, 
      Vanderbilt University Medical School, Nashville, TN, 37232, USA.
AD  - Laboratory of Food and Health, Research Group on Quality, Safety and Bioactivity 
      of Plant Foods, Dept. Food Science and Technology, CEBAS-CSIC, P.O. Box 164, 
      Murcia, Campus de Espinardo, 30100, Spain.
FAU - Gonzalez-Sarrias, Antonio
AU  - Gonzalez-Sarrias A
AUID- ORCID: 0000-0002-3407-0678
AD  - Laboratory of Food and Health, Research Group on Quality, Safety and Bioactivity 
      of Plant Foods, Dept. Food Science and Technology, CEBAS-CSIC, P.O. Box 164, 
      Murcia, Campus de Espinardo, 30100, Spain.
FAU - Espin, Juan Carlos
AU  - Espin JC
AUID- ORCID: 0000-0002-1068-8692
AD  - Laboratory of Food and Health, Research Group on Quality, Safety and Bioactivity 
      of Plant Foods, Dept. Food Science and Technology, CEBAS-CSIC, P.O. Box 164, 
      Murcia, Campus de Espinardo, 30100, Spain.
FAU - Schneider, Claus
AU  - Schneider C
AUID- ORCID: 0000-0003-4215-967X
AD  - Department of Pharmacology and Vanderbilt Institute of Chemical Biology, 
      Vanderbilt University Medical School, Nashville, TN, 37232, USA.
LA  - eng
GR  - 16POST30690001/AHA/American Heart Association-American Stroke Association/United 
      States
GR  - R01 GM076592/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20200504
PL  - Germany
TA  - Mol Nutr Food Res
JT  - Molecular nutrition & food research
JID - 101231818
RN  - 0 (Anti-Inflammatory Agents, Non-Steroidal)
RN  - 0 (Coumarins)
RN  - 0 (Eicosanoids)
RN  - 0 (Hydrolyzable Tannins)
RN  - 0 (Hydroxyeicosatetraenoic Acids)
RN  - 0 (urolithin B)
RN  - 0 (urolithin C)
RN  - 1143-70-0 (3,8-dihydroxy-6H-dibenzo(b,d)pyran-6-one)
RN  - 1HGW4DR56D (Leukotriene B4)
RN  - 467RNW8T91 (5-hydroxy-6,8,11,14-eicosatetraenoic acid)
RN  - EC 1.13.11.34 (Arachidonate 5-Lipoxygenase)
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
RN  - EC 1.14.99.1 (PTGS2 protein, human)
RN  - K7Q1JQR04M (Dinoprostone)
SB  - IM
MH  - Animals
MH  - Anti-Inflammatory Agents, Non-Steroidal/chemistry/*pharmacology
MH  - Arachidonate 5-Lipoxygenase/*metabolism
MH  - Coumarins/pharmacology
MH  - Cyclooxygenase 2/metabolism
MH  - Dinoprostone/metabolism
MH  - Eicosanoids/*metabolism
MH  - Humans
MH  - Hydrolyzable Tannins/pharmacology
MH  - Hydroxyeicosatetraenoic Acids/metabolism
MH  - Leukocytes/drug effects/metabolism
MH  - Leukotriene B4/metabolism
MH  - Mice
MH  - RAW 264.7 Cells
PMC - PMC7297467
MID - NIHMS1586058
OTO - NOTNLM
OT  - 5-lipoxygenase
OT  - cyclooxygenase-2
OT  - eicosanoid
OT  - inflammatory bowel disease
OT  - urolithins
COIS- Conflict of interest Authors declare not having any financial or personal 
      interest, nor having an association with any individuals or organizations that 
      could have influenced inappropriately the submitted work.
EDAT- 2020/04/20 06:00
MHDA- 2021/07/16 06:00
PMCR- 2021/06/01
CRDT- 2020/04/20 06:00
PHST- 2020/02/09 00:00 [received]
PHST- 2020/03/27 00:00 [revised]
PHST- 2020/04/20 06:00 [pubmed]
PHST- 2021/07/16 06:00 [medline]
PHST- 2020/04/20 06:00 [entrez]
PHST- 2021/06/01 00:00 [pmc-release]
AID - 10.1002/mnfr.202000129 [doi]
PST - ppublish
SO  - Mol Nutr Food Res. 2020 Jun;64(11):e2000129. doi: 10.1002/mnfr.202000129. Epub 
      2020 May 4.