Dietary blue pigments derived from genipin, attenuate inflammation by inhibiting LPS-induced iNOS and COX-2 expression via the NF-κB inactivation.

Abstract

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-α) was inhibited, moreover, ELISA results showed that the productions of IL-6 and TNF-α 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-κB) 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 κB (IκB) α, Inhibitor of NF-κB Kinase (IKK) α, IKK-β, and phosphorylation of IκB-α. 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-α 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-1β, and TNF-α expression through the down-regulation of NF-κB 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.

• Authors: Qiang-Song Wang, Yaozu Xiang, Yuan-Lu Cui, Ke-Ming Lin, Xin-Fang Zhang
• Journal: PloS one (PLoS One) Vol. 7 Issue 3 Pg. e34122 ( 2012) ISSN: 1932-6203 [Electronic] United States
• PMID: 22479539 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cytokines
• Iridoids
• Lipopolysaccharides
• NF-kappa B
• Nitrites
• genipin
• Nitric Oxide Synthase Type II
• Cyclooxygenase 2
• Dinoprostone

Topics

• Animals
• Cell Line
• Cyclooxygenase 2 (metabolism)
• Cytokines (metabolism)
• Dinoprostone (metabolism)
• Gene Expression Regulation, Enzymologic
• Inflammation
• Iridoids (chemistry, metabolism)
• Lipopolysaccharides (metabolism)
• Macrophages (cytology)
• Male
• Mice
• Mice, Inbred ICR
• Models, Chemical
• NF-kappa B (metabolism)
• Nitric Oxide Synthase Type II (metabolism)
• Nitrites (chemistry)
• Pigmentation