PMID- 22479539
OWN - NLM
STAT- MEDLINE
DCOM- 20121105
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 7
IP  - 3
DP  - 2012
TI  - Dietary blue pigments derived from genipin, attenuate inflammation by inhibiting 
      LPS-induced iNOS and COX-2 expression via the NF-kappaB inactivation.
PG  - e34122
LID - 10.1371/journal.pone.0034122 [doi]
LID - e34122
AB  - BACKGROUND AND PURPOSE: The edible blue pigments produced by gardenia fruits have 
      been used as value-added colorants for foods in East Asia for 20 years. However, 
      the biological activity of the blue pigments derived from genipin has not been 
      reported. METHODOLOGY/PRINCIPAL FINDINGS: The anti-inflammatory effect of blue 
      pigments was studied in lipopolysaccharide (LPS) stimulated RAW 264.7 macrophage 
      in vitro. The secretions of nitric oxide (NO) and prostaglandin E(2) (PGE(2)) 
      were inhibited in concentration-dependent manner by blue pigments. Real-time 
      reverse-transcription polymerase chain reaction (Real-time RT-PCR) analyses 
      demonstrated that the mRNA expression of inducible nitric oxide synthase (iNOS), 
      cyclooxygenase-2 (COX-2), interleukin (IL)-6, and tumor necrosis factor alpha 
      (TNF-alpha) was inhibited, moreover, ELISA results showed that the productions of 
      IL-6 and TNF-alpha were inhibited. Cell-based ELISA revealed the COX-2 protein 
      expression was inhibited. The proteome profiler array showed that 12 cytokines 
      and chemokines involved in the inflammatory process were down-regulated by blue 
      pigments. Blue pigments inhibited the nuclear transcription factor kappa-B 
      (NF-kappaB) activation induced by LPS, and this was associated with decreasing the 
      DNA-binding activity of p65 and p50. Furthermore, blue pigments suppressed the 
      degradation of inhibitor of kappaB (IkappaB) alpha, Inhibitor of NF-kappaB Kinase (IKK) alpha, IKK-beta, 
      and phosphorylation of IkappaB-alpha. The anti-inflammatory effect of blue pigments in 
      vivo was studied in carrageenan-induced paw edema and LPS-injecting ICR mice. 
      Finally, blue pigments significantly inhibited paw swelling and reduced plasma 
      TNF-alpha and IL-6 production in vivo. CONCLUSIONS AND IMPLICATIONS: These results 
      suggest that the anti-inflammatory properties of blue pigments might be the 
      results from the inhibition of iNOS, COX-2, IL-6, IL-1beta, and TNF-alpha expression 
      through the down-regulation of NF-kappaB activation, which will provide strong 
      scientific evidence for the edible blue pigments to be developed as a new 
      health-enhancing nutritional food for the prevention and treatment of 
      inflammatory diseases.
FAU - Wang, Qiang-Song
AU  - Wang QS
AD  - Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of 
      Traditional Chinese Medicine, Tianjin, People's Republic of China.
FAU - Xiang, Yaozu
AU  - Xiang Y
FAU - Cui, Yuan-Lu
AU  - Cui YL
FAU - Lin, Ke-Ming
AU  - Lin KM
FAU - Zhang, Xin-Fang
AU  - Zhang XF
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120330
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Cytokines)
RN  - 0 (Iridoids)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (NF-kappa B)
RN  - 0 (Nitrites)
RN  - A3V2NE52YG (genipin)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
RN  - K7Q1JQR04M (Dinoprostone)
SB  - IM
MH  - Animals
MH  - Cell Line
MH  - Cyclooxygenase 2/*metabolism
MH  - Cytokines/metabolism
MH  - Dinoprostone/metabolism
MH  - *Gene Expression Regulation, Enzymologic
MH  - Inflammation
MH  - Iridoids/*chemistry/metabolism
MH  - Lipopolysaccharides/*metabolism
MH  - Macrophages/cytology
MH  - Male
MH  - Mice
MH  - Mice, Inbred ICR
MH  - Models, Chemical
MH  - NF-kappa B/*metabolism
MH  - Nitric Oxide Synthase Type II/*metabolism
MH  - Nitrites/chemistry
MH  - Pigmentation
PMC - PMC3316609
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2012/04/06 06:00
MHDA- 2012/11/06 06:00
PMCR- 2012/03/30
CRDT- 2012/04/06 06:00
PHST- 2011/09/10 00:00 [received]
PHST- 2012/02/22 00:00 [accepted]
PHST- 2012/04/06 06:00 [entrez]
PHST- 2012/04/06 06:00 [pubmed]
PHST- 2012/11/06 06:00 [medline]
PHST- 2012/03/30 00:00 [pmc-release]
AID - PONE-D-11-17762 [pii]
AID - 10.1371/journal.pone.0034122 [doi]
PST - ppublish
SO  - PLoS One. 2012;7(3):e34122. doi: 10.1371/journal.pone.0034122. Epub 2012 Mar 30.