Dietary Blue Pigments Derived from Genipin, Attenuate Inflammation by Inhibiting LPS-Induced iNOS and COX-2 Expression via the NF-kappa B Inactivation

作者：Wang, Qiang-Song; Xiang, Yaozu; Cui, Yuan-Lu^*; Lin, Ke-Ming; Zhang, Xin-Fang

来源：PLos One, 2012, 7(3): e34122.

DOI：10.1371/journal.pone.0034122

• NITRIC-OXIDE SYNTHASE
• RAW 264.7 MACROPHAGES
• STIMULATED RAW264.7 MACROPHAGES
• THERAPEUTIC TARGET
• ALPHA PRODUCTION
• GARDENIA FRUITS
• GENE-EXPRESSION
• L-ARGININE
• TNF-ALPHA
• CELLS

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-kappa B) 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 kappa B (I kappa B) alpha, Inhibitor of NF-kappa B Kinase (IKK) alpha, IKK-beta, and phosphorylation of I kappa B-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-1 beta, and TNF-alpha expression through the down-regulation of NF-kappa B 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.

• 出版日期2012-3-30
• 单位天津中医药大学