Cyanidin-3-O-beta-glucoside inhibits iNOS 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 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.
Wang
Qing
Q
Department of Nutrition, School of Public Health, Sun Yat-sen University (Northern Campus), 74 Zhongshan Road 2, Guangzhou, PR China.
Xia
Min
M
Liu
Chi
C
Guo
Honghui
H
Ye
Qingyuan
Q
Hu
Yan
Y
Zhang
Yinghui
Y
Hou
Mengjun
M
Zhu
Huilian
H
Ma
Jing
J
Ling
Wenhua
W
D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000872:Anthocyanins / Q000494:pharmacology*; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000187:drug effects* / Q000378:metabolism; D015232:Dinoprostone / Q000096:biosynthesis; D005960:Glucosides / Q000494:pharmacology*; D006801:Humans; D000071518:Liver X Receptors; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors*; D057093:Orphan Nuclear Receptors; D047495:PPAR gamma / Q000235:genetics; D018160:Receptors, Cytoplasmic and Nuclear / Q000187:drug effects* / Q000378:metabolism
D000872:Anthocyanins; D000893:Anti-Inflammatory Agents; D052246:Cyclooxygenase 2 Inhibitors; D004268:DNA-Binding Proteins; D005960:Glucosides; D000071518:Liver X Receptors; D016328:NF-kappa B; C000605213:NR1H3 protein, human; D057093:Orphan Nuclear Receptors; D047495:PPAR gamma; D018160:Receptors, Cytoplasmic and Nuclear; C462279:cyanidin-3-O-beta-glucopyranoside; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D015232:Dinoprostone