Inhibitory effects of tilianin on the expression of inducible nitric oxide synthase in low density lipoprotein receptor deficiency mice

Ki-Hoan Nam,Jae-Hoon Choi,Goo Taeg Oh,Mi-Ni Lee,Yun-Jeong Seo,Mi-Ran Lee,Hyeong-Kyu Lee,Young-Mi Lee,Hyoung-Chin Kim,Yong-Sung Won,Jong-Gil Park,Chul-Ho Lee,Young-Myeong Kim,Sei-Ryang Oh

doi:10.1038/emm.2006.52

Abstract

We investigated the effect of tilianin upon inducible nitric oxide synthesis in the plasma of low-density lipoprotein receptor knock-out (Ldlr-/-) mice fed with high cholesterol diet and in primary peritoneal macrophages of Ldlr-/- mice. High cholesterol diet induced nitric oxide production in the plasma of Ldlr-/- mice. Tilianin reduced the level of nitric oxide (NO) in plasma from Ldlr-/- mice induced by the high cholesterol diet. Tilianin also inhibited the NO production from the primary culture of peritoneal macrophages treated with lipopolysaccharide. The inhibition of NO production was caused by the suppression of inducible nitric oxide synthase (iNOS) gene expression in peritoneal macrophages isolated from Ldlr-/- mice. Moreover, tilianin inhibited the transcriptional activation of iNOS promoter that has NF-kappaB binding element. Thus, these results provide the first evidence that tilianin inhibit iNOS expression and production of NO and may act as a potential anti-inflammatory agent.

Highlights

nitric oxide (NO) is a gaseous free radical with very short half-life in biological system and can act both as a weak oxidant and as a reductant (Kanner et al, 1991)
We have reported that tilianin, a major component of Agastache rugosa (Labiatae) significantly inhibits the tumor necrotic factor- (TNF- )-induced expression of vascular cell adhesion molecule-1 (VCAM-1) in human umbilical vein endothelial cells (HUVEC) as its potential antiatherogenic mechanism (Hong et al, 2001; Nam et al, 2005)
Nitrotyrosine, was detected in the corresponding lesion site in which prominent inducible NOS (iNOS) expression was detected (Figure 1B). These results indicate that iNOS expression in atheromatous plaques is associated with the formation of nitrotyrosine

Summary

Introduction

NO is a gaseous free radical with very short half-life in biological system and can act both as a weak oxidant and as a reductant (Kanner et al, 1991). NO is synthesized in mammals by the nitric oxide synthases (NOS). There are three NOS isoforms: endothelial NOS (eNOS), neuronal NOS (nNOS), and inducible NOS (iNOS). Unlike eNOS and nNOS, iNOS is not constitutively expressed in macrophages and smooth muscle cells of inflammatory vascular tissues. All three isoforms can be demonstrated (Wilcox et al, 1997). INOS expression has been localized to vascular smooth muscle cells and mononuclear leukocytes in early and advanced atherosclerosis (Esaki et al, 1997)

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Conclusion