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Cyanidin-3-O-beta-glucoside Inhibits iNOS and COX-2 Expression by Inducing Liver X Receptor Alpha Activation in THP-1 Macrophages

Cyanidin-3-O-beta-glucoside Inhibits iNOS and COX-2 Expression by Inducing Liver X Receptor Alpha Activation in THP-1 Macrophages

Qing Wang, Min Xia, Chi Liu, Honghui Guo, Qingyuan Ye, Yan Hu, Yinghui Zhang, Mengjun Hou, Huilian Zhu, Jing Ma, Wenhua Ling

Life Sci. 2008 Aug 1;83(5-6):176-84.

PMID: 18619979

Abstract:

Anthocyanins belong to a large and widespread group of water-soluble phytochemicals 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-glucoside (C3G) for 12 h can enhance the expression and transcriptional activities of the nuclear receptor peroxisome proliferator-activated receptor gamma (PPARgamma) and liver X receptor alpha (LXRalpha). 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 LXRalpha antagonist, significantly downregulates the inhibitory effect of C3G on LPS-induced iNOS and COX-2 expression in THP-1 macrophages, whereas the PPARgamma antagonist GW9662 has no effect. Further investigation revealed that LXRalpha might interfere with LPS-induced iNOS and COX-2 expression by suppressing the functional activation of nuclear factor-kappaB (NF-kappaB), not - as was previously proposed - by reducing NF-kappaB nuclear translocation. Taken together, these results indicate that LXRalpha 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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
ALP6699203	Geranylgeranyl pyrophosphate ammonium salt		6699-20-3 (free acid)	Price

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