2-hydroxy-4'-methoxychalcone inhibits proliferation and inflammation of human aortic smooth muscle cells by increasing the expression of peroxisome proliferator-activated receptor gamma.

Abstract:

:Chalcone is a class of flavonoid compounds that are widely biosynthesized in plants. Epidemiological studies suggest that increased intake of flavonoids from fruits and vegetables reduces the risk of cardiovascular disease. However, the effect of chalcone on cardiovascular diseases has not been fully investigated. The aims of this study were to evaluate the antiatherosclerotic effect of 2-hydroxy-4'-methoxychalcone (AN07, a synthetic chalcone derivate) and to investigate its potential pharmacological mechanisms. Oxidized low-density lipoprotein (Ox-LDL) has been reported to stimulate proliferation of human aortic smooth muscle cells and that is one of the mechanisms resulting in atherosclerosis. In this study, we demonstrate that AN07 significantly inhibits the Ox-LDL-induced proliferation of human aortic smooth muscle cells. This effect is mediated via the inhibition of p44/42 mitogen-activated protein kinase and E-twenty six 1 phosphorylations. In the effect of anti-inflammation, AN07 decreases the Ox-LDL-stimulated upregulation of interleukin (IL) 1β and IL-6. In addition, AN07 acts synergistically with rosiglitazone and pioglitazone to inhibit the Ox-LDL-induced proliferation of human aortic smooth muscle cells and upregulation of cyclin D1, cyclin D3, IL-1β, and IL-6. These effects are a result of an increase in peroxisome proliferator-activated receptor gamma mRNA and protein expression stimulated by AN07 in human aortic smooth muscle cells. In conclusion, the chalcone derivate AN07 has versatile therapeutic potential against atherosclerosis by acting as peroxisome proliferator-activated receptor gamma inducer, p44/42 mitogen-activated protein kinase inhibitor, and cell cycle blocker.

journal_name

J Cardiovasc Pharmacol

authors

Liu CS,Chang CC,Du YC,Chang FR,Wu YC,Chang WC,Hsieh TJ

doi

10.1097/FJC.0b013e3182440486

subject

Has Abstract

pub_date

2012-04-01 00:00:00

pages

339-51

issue

4

eissn

0160-2446

issn

1533-4023

journal_volume

59

pub_type

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