PMID- 23506745
OWN - NLM
STAT- MEDLINE
DCOM- 20131021
LR  - 20211021
IS  - 1475-2662 (Electronic)
IS  - 0007-1145 (Print)
IS  - 0007-1145 (Linking)
VI  - 110
IP  - 4
DP  - 2013 Aug
TI  - Protective effect of naringenin against experimental colitis via suppression of 
      Toll-like receptor 4/NF-kappaB signalling.
PG  - 599-608
LID - 10.1017/S0007114512005594 [doi]
AB  - Naringenin, one of the most abundant flavonoids in citrus, grapefruits and 
      tomatoes, has been used as a traditional anti-inflammatory agent for centuries. 
      However, the molecular mechanism of naringenin in intestinal inflammation remains 
      unknown so far. The present study investigated a molecular basis for the 
      protective effect of naringenin in dextran sulphate sodium-induced murine 
      colitis. Pre-administration of naringenin significantly reduced the severity of 
      colitis and resulted in down-regulation of pro-inflammatory mediators (inducible 
      NO synthase (iNOS), intercellular adhesion molecule-1 (ICAM-1), monocyte 
      chemoattractant protein-1 (MCP-1), cyclo-oxygenase-2 (Cox2), TNF-alpha and IL-6 mRNA) 
      in the colon mucosa. The decline in the production of pro-inflammatory cytokines, 
      specifically TNF-alpha and IL-6, correlated with a decrease in mucosal Toll-like 
      receptor 4 (TLR4) mRNA and protein. Phospho-NF-kappaB p65 protein was significantly 
      decreased, which correlated with a similar decrease in phospho-IkappaBalpha protein. 
      Consistent with the in vivo results, naringenin exposure blocked 
      lipopolysaccharide-stimulated nuclear translocation of NF-kappaB p65 in mouse 
      macrophage RAW264.7 cells. In addition, in vitro NF-kappaB reporter assays performed 
      on human colonic HT-29 cells exposed to naringenin demonstrated a significant 
      inhibition of TNF-alpha-induced NF-kappaB luciferase expression. Thus, for the first 
      time, the present study indicates that targeted inhibition of the TLR4/NF-kappaB 
      signalling pathway might be an important mechanism for naringenin in abrogating 
      experimental colitis.
FAU - Dou, Wei
AU  - Dou W
AD  - Shanghai Key Laboratory of Formulated Chinese Medicines and MOE Key Laboratory 
      for Standardization of Chinese Medicines, Institute of Chinese Materia Medica, 
      Shanghai University of Traditional Chinese Medicine, Shanghai 201203, People's 
      Republic of China.
FAU - Zhang, Jingjing
AU  - Zhang J
FAU - Sun, Aning
AU  - Sun A
FAU - Zhang, Eryun
AU  - Zhang E
FAU - Ding, Lili
AU  - Ding L
FAU - Mukherjee, Subhajit
AU  - Mukherjee S
FAU - Wei, Xiaohui
AU  - Wei X
FAU - Chou, Guixin
AU  - Chou G
FAU - Wang, Zheng-Tao
AU  - Wang ZT
FAU - Mani, Sridhar
AU  - Mani S
LA  - eng
GR  - R01 CA127231/CA/NCI NIH HHS/United States
GR  - R01 CA161879/CA/NCI NIH HHS/United States
GR  - R01CA127231/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20130318
PL  - England
TA  - Br J Nutr
JT  - The British journal of nutrition
JID - 0372547
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Cytokines)
RN  - 0 (Flavanones)
RN  - 0 (Flavonoids)
RN  - 0 (NF-kappa B)
RN  - 0 (Tlr4 protein, mouse)
RN  - 0 (Toll-Like Receptor 4)
RN  - 9042-14-2 (Dextran Sulfate)
RN  - EC 1.13.12.- (Luciferases)
RN  - HN5425SBF2 (naringenin)
SB  - IM
MH  - Animals
MH  - Anti-Inflammatory Agents/pharmacology
MH  - Cell Line
MH  - Colitis/*chemically induced/*prevention & control
MH  - Cytokines/metabolism
MH  - Dextran Sulfate/pharmacology
MH  - Dietary Supplements
MH  - Female
MH  - Flavanones/*pharmacology
MH  - Flavonoids/pharmacology
MH  - Inflammation
MH  - Luciferases/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - NF-kappa B/*metabolism
MH  - Signal Transduction
MH  - Toll-Like Receptor 4/*metabolism
PMC - PMC3726555
MID - NIHMS458855
COIS- The authors have no conflicts of interest to declare.
EDAT- 2013/03/20 06:00
MHDA- 2013/10/22 06:00
PMCR- 2013/08/07
CRDT- 2013/03/20 06:00
PHST- 2013/03/20 06:00 [entrez]
PHST- 2013/03/20 06:00 [pubmed]
PHST- 2013/10/22 06:00 [medline]
PHST- 2013/08/07 00:00 [pmc-release]
AID - S0007114512005594 [pii]
AID - 10.1017/S0007114512005594 [doi]
PST - ppublish
SO  - Br J Nutr. 2013 Aug;110(4):599-608. doi: 10.1017/S0007114512005594. Epub 2013 Mar 
      18.