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

Wang QS, Xiang Y, Cui YL, Lin KM, Zhang XF - PLoS ONE (2012)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, People's Republic of China.

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.

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Effect of blue pigments on LPS-induced TNF-α, IL-6, PGE2 production and COX-2 protein expression.RAW 264.7 cells were incubated with the indicated concentrations of blue pigments and 0.2 µg/mL LPS for 18 h or 24 h. TNF-α (A), IL-6 (B), PGE2 (C) in the culture medium were analyzed by ELISA, and the COX-2 protein expression (D) was analyzed by cell-based ELISA. Data represent means ±S.D. values from three independent experiments. * P<0.05, ** P<0.01 (n = 6) compared with LPS treated cells alone.
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pone-0034122-g003: Effect of blue pigments on LPS-induced TNF-α, IL-6, PGE2 production and COX-2 protein expression.RAW 264.7 cells were incubated with the indicated concentrations of blue pigments and 0.2 µg/mL LPS for 18 h or 24 h. TNF-α (A), IL-6 (B), PGE2 (C) in the culture medium were analyzed by ELISA, and the COX-2 protein expression (D) was analyzed by cell-based ELISA. Data represent means ±S.D. values from three independent experiments. * P<0.05, ** P<0.01 (n = 6) compared with LPS treated cells alone.

Mentions: TNF-α, IL-6 are known to be pro-inflammatory cytokines that posses a multitude of biological activities linked to the immune-pathology of acute or chronic inflammatory diseases. After treatment with blue pigments and activated with LPS (0.2 µg/mL), the secretion of IL-6 and TNF-α were detected by ELISA. As shown in Figure 3A–B, pretreatment of RAW 264.7 cells with blue pigments (25, 50, 100 µM) significantly reduced IL-6 production (P<0.01), whereas TNF-α production were only inhibited slightly by 50 µM blue pigments (P<0.05).


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

Wang QS, Xiang Y, Cui YL, Lin KM, Zhang XF - PLoS ONE (2012)

Effect of blue pigments on LPS-induced TNF-α, IL-6, PGE2 production and COX-2 protein expression.RAW 264.7 cells were incubated with the indicated concentrations of blue pigments and 0.2 µg/mL LPS for 18 h or 24 h. TNF-α (A), IL-6 (B), PGE2 (C) in the culture medium were analyzed by ELISA, and the COX-2 protein expression (D) was analyzed by cell-based ELISA. Data represent means ±S.D. values from three independent experiments. * P<0.05, ** P<0.01 (n = 6) compared with LPS treated cells alone.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3316609&req=5

pone-0034122-g003: Effect of blue pigments on LPS-induced TNF-α, IL-6, PGE2 production and COX-2 protein expression.RAW 264.7 cells were incubated with the indicated concentrations of blue pigments and 0.2 µg/mL LPS for 18 h or 24 h. TNF-α (A), IL-6 (B), PGE2 (C) in the culture medium were analyzed by ELISA, and the COX-2 protein expression (D) was analyzed by cell-based ELISA. Data represent means ±S.D. values from three independent experiments. * P<0.05, ** P<0.01 (n = 6) compared with LPS treated cells alone.
Mentions: TNF-α, IL-6 are known to be pro-inflammatory cytokines that posses a multitude of biological activities linked to the immune-pathology of acute or chronic inflammatory diseases. After treatment with blue pigments and activated with LPS (0.2 µg/mL), the secretion of IL-6 and TNF-α were detected by ELISA. As shown in Figure 3A–B, pretreatment of RAW 264.7 cells with blue pigments (25, 50, 100 µM) significantly reduced IL-6 production (P<0.01), whereas TNF-α production were only inhibited slightly by 50 µM blue pigments (P<0.05).

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, People's Republic of China.

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.

Show MeSH
Related in: MedlinePlus