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

Chin San Liu, Chen Chia Chang, Ying Chi Du, Fang Rong Chang, Yang Chang Wu, Wei Chiao Chang, Tusty Jiuan Hsieh

Research output: Contribution to journalArticle

11 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)339-351
Number of pages13
JournalJournal of Cardiovascular Pharmacology
Volume59
Issue number4
DOIs
Publication statusPublished - Apr 2012
Externally publishedYes

Fingerprint

Chalcone
PPAR gamma
Smooth Muscle Myocytes
Inflammation
rosiglitazone
pioglitazone
Mitogen-Activated Protein Kinases
Interleukin-1
Flavonoids
Interleukin-6
Atherosclerosis
Cardiovascular Diseases
Up-Regulation
Cyclin D3
Cyclin D1
Protein Kinase Inhibitors
Vegetables
Epidemiologic Studies
Fruit
Cell Cycle

Keywords

  • atherosclerosis
  • chalcone
  • flavonoid
  • IL-6
  • Ox-LDL
  • PPARg

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

Cite this

2-hydroxy-4-methoxychalcone inhibits proliferation and inflammation of human aortic smooth muscle cells by increasing the expression of peroxisome proliferator-activated receptor gamma. / Liu, Chin San; Chang, Chen Chia; Du, Ying Chi; Chang, Fang Rong; Wu, Yang Chang; Chang, Wei Chiao; Hsieh, Tusty Jiuan.

In: Journal of Cardiovascular Pharmacology, Vol. 59, No. 4, 04.2012, p. 339-351.

Research output: Contribution to journalArticle

@article{f371412a74074b90894d5fcfa536e364,
title = "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.",
keywords = "atherosclerosis, chalcone, flavonoid, IL-6, Ox-LDL, PPARg",
author = "Liu, {Chin San} and Chang, {Chen Chia} and Du, {Ying Chi} and Chang, {Fang Rong} and Wu, {Yang Chang} and Chang, {Wei Chiao} and Hsieh, {Tusty Jiuan}",
year = "2012",
month = "4",
doi = "10.1097/FJC.0b013e3182440486",
language = "English",
volume = "59",
pages = "339--351",
journal = "Journal of Cardiovascular Pharmacology",
issn = "0160-2446",
publisher = "Lippincott Williams and Wilkins",
number = "4",

}

TY - JOUR

T1 - 2-hydroxy-4-methoxychalcone inhibits proliferation and inflammation of human aortic smooth muscle cells by increasing the expression of peroxisome proliferator-activated receptor gamma

AU - Liu, Chin San

AU - Chang, Chen Chia

AU - Du, Ying Chi

AU - Chang, Fang Rong

AU - Wu, Yang Chang

AU - Chang, Wei Chiao

AU - Hsieh, Tusty Jiuan

PY - 2012/4

Y1 - 2012/4

N2 - 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.

AB - 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.

KW - atherosclerosis

KW - chalcone

KW - flavonoid

KW - IL-6

KW - Ox-LDL

KW - PPARg

UR - http://www.scopus.com/inward/record.url?scp=84859882663&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84859882663&partnerID=8YFLogxK

U2 - 10.1097/FJC.0b013e3182440486

DO - 10.1097/FJC.0b013e3182440486

M3 - Article

C2 - 22157260

AN - SCOPUS:84859882663

VL - 59

SP - 339

EP - 351

JO - Journal of Cardiovascular Pharmacology

JF - Journal of Cardiovascular Pharmacology

SN - 0160-2446

IS - 4

ER -