Abstract
Background and PurposeThe 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 FindingsThe 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 E2 (PGE2) 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 ImplicationsThese 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.
Highlights
With growing concern on the safety of synthetic dyes, the importance of natural colorants suitable for using in foods has gained increasing attention
Blue pigments significantly inhibited paw swelling and reduced plasma tumor necrosis factor alpha (TNF-a) and IL-6 production in vivo. These results suggest that the anti-inflammatory properties of blue pigments might be the results from the inhibition of inducible nitric oxide synthase (iNOS), COX-2, IL-6, IL-1b, and TNF-a expression through the down-regulation of nuclear transcription factor kappa-B (NF-kB) activation, which will provide strong scientific evidence for the edible blue pigments to be developed as a new healthenhancing nutritional food for the prevention and treatment of inflammatory diseases
The results showed that the effect of blue pigments on mRNA expression of TNF-a, IL-6, iNOS, COX-2 was coincidence with the secretion of TNF-a, IL-6, nitric oxide (NO), PEG2 that in culture medium
Summary
With growing concern on the safety of synthetic dyes, the importance of natural colorants suitable for using in foods has gained increasing attention. Genipin itself is colorless but it reacts spontaneously with amino acids to form blue pigments which are used in food industry widely [1]. The edible blue pigments produced by gardenia fruits have been widely used as a blue food colorant in East Asia [2]. Macrophages play an important role in inflammatory disease and host defense through the release of factors such as NO, prostaglandin mediators, and cytokines involved in the immune response [5,6,7]. PGE2 is another important mediator which is produced from arachidonic acid metabolites which are catalyzed by COX-2 in inflammatory responses [13]. The edible blue pigments produced by gardenia fruits have been used as value-added colorants for foods in East Asia for 20 years. The biological activity of the blue pigments derived from genipin has not been reported
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