Submitted to: Inflammation Research
Publication Type: Peer reviewed journal
Publication Acceptance Date: 3/1/2010
Publication Date: 3/3/2010
Citation: Zhang, Y., Lian, F., Zhu, Y., Xia, M., Wang, Q., Ling, W., Wang, X. 2010. Cyanidin-3-O-beta-glucoside inhibits LPS-induced expression of inflammatory mediators through decreasing IkBa Phosphorylation in THP-1 Cells. Inflammation Research. 59(9):723-730. Interpretive Summary: Cyanidin 3-glucoside (C3G), a common polyphenol in many fruits such as blueberry has been suggested as an anti-inflammatory agent. In this study, we used a cell culture model to explore the molecular mechanisms of the anti-inflammation action of C3G. We found that in cultured macrophage cells, C3G inhibited pathogen-stimulated production and release of two compounds mediating inflammatory response and inhibition of C3G was mediated by blocking inflammatory signaling pathway. These results are useful for identifying the potential benefits of blueberry.
Technical Abstract: Objective and design: As a common phytochemical, cyanidin 3-O-beta-glucoside (C3G) has a role in inhibiting inflammatory mediators; however, its mechanism of action remains unclear. The purpose of this study was to explore the effect of C3G on lipopolysaccharide (LPS)-stimulated TNFa and IL-6 expression in the human monocyte/ macrophage cell line THP-1, and to explore the mechanisms involved. Methods: Differentiated THP-1 cells were treated with different concentrations of C3G (0.005, 0.05, 0.5,10 uM) in the absence or presence of 1 ng/mL LPS. mRNA expression levels were detected by real time PCR, and secretion of TNFa and IL-6, phosphorylated I'Ba, and nuclear factor-kappa B (NF-'B) P65 were monitored by ELISA or Western blotting analysis. The role of an inhibitor of I'Ba phosphorylation, BAY 11-7082, in C3G inhibition of LPS-induced cytokines expression was investigated. Results: C3G (0.05–0.5 uM) treatment significantly inhibited LPS-stimulated TNFa and IL-6 mRNA expression and secretion of these proteins by THP-1 cells. Phosphorylation of I'Ba and NF-'B nuclear translocation could be blocked by 0.5 µM C3G. BAY 11-7082 treatment abolished C3G-induced reduction of TNFa and IL-6. Conclusion: Our results suggest that C3G exerts its anti-inflammatory effect through inhibiting I'Ba phosphorylation, thereby suppressing NF-'B activity in THP-1 cells.