Cyanidin-3-O-β-glucoside inhibits NOS and COX-2 expression by inducing liver X receptor alpha activation in THP-1 macrophages

Anthocyanins belong to a large and widespread group of water-soluble phytochernicals and exhibit potent antioxidative and anti-inflammatory properties; however, the molecular mechanisms of these biochemical actions mediated by anthocyanins remain unclear. In this study, our data show that pretreatment of THP-1 macrophages with Cyanidin-3-O-beta-glucosicle (C3G) for 12 h can enhance the expression and transcriptional activities of the nuclear receptor peroxisome proliferator-activated receptor gamma (PPAR gamma) and liver X receptor a (LXR alpha). Furthermore, pretreatment of these cells with C3G for 12 h causes dose-dependent inhibition of lipopolysaccharide (LPS)-induced nitric Oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) at both the mRNA and protein levels together with a decrease in nitric oxide (NO) and prostaglandin E-2 (PGE(2)) production. Consequently, addition of geranylgeranyl pyrophosphate ammonium salt (GGPP), an LXR alpha antagonist, significantly downregutates the inhibitory effect of C3G on LPS-induced iNOS and COX-2 expression in THP-1 macrophages, whereas the PPAR-gamma antagonist GW9662 has no effect. Further investigation revealed that LXRa might interfere with LPS-induced iNOS and COX-2 expression by suppressing the functional activation of nuclear factor-kappa B (NF-kappa B), not - as was previously proposed - by reducing NF-kappa B nuclear translocation. Taken together, these results indicate that LXR alpha activation has an essential role in the anti-inflammatory property of C3G. Moreover, they provide new insight into the molecular basis for the anti-inflammatory property of anthocyanins. (C) 2008 Elsevier Inc. All rights reserved.