Ursolic acid modulates MMPs, collagen-I, α-SMA, and TGF-β expression in isoproterenol-induced myocardial infarction in rats

T. Radhiga, Senthil Selvaraj, A. Sundaresan, K. V. Pugalendi

Research output: Contribution to journalArticle

Abstract

In the present study, the modulatory effect of ursolic acid (UA) on cardiac fibrosis and mitochondrial and lysosomal enzymes activity in isoproterenol-induced myocardial infarction (MI) in rats were examined. Isoproterenol hydrochloride (ISO; 85 mg/kg body weight) was administered subcutaneously for first two consecutive days. ISO-induced MI in rats significantly decreased the activities of mitochondrial tricarboxylic acid cycle enzymes and respiratory chain enzymes while increased the activities of lysosomal glycohydrolases and cathepsins. The expression of matrix metalloproteinase 2 (MMP-2), MMP-9, collagen type I, α-smooth muscle actin (α-SMA), and transforming growth factor-β (TGF-β) were upregulated in ISO-induced MI in rats. UA administration to rats showed increased activities of mitochondrial tricarboxylic acid cycle enzymes and respiratory chain enzymes and decreased activities of lysosomal glycohydrolases and cathepsins in ISO-induced rats. Furthermore, expression of MMP-2, MMP-9, collagen type I, α-SMA, and TGF-β downregulated in UA-administered rats. Thus, our results demonstrate that UA has an anti-fibrotic effect and attenuates the mitochondrial and lysosomal dysfunction in ISO-induced MI in rats.

Original languageEnglish
JournalHuman and Experimental Toxicology
DOIs
Publication statusPublished - 1 Jan 2019

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Transforming Growth Factors
Matrix Metalloproteinases
Isoproterenol
Rats
Collagen
Myocardial Infarction
Enzymes
Cathepsins
Citric Acid Cycle
Glycoside Hydrolases
Matrix Metalloproteinase 2
Electron Transport
Collagen Type I
Enzyme activity
ursolic acid
Smooth Muscle
Muscle
Actins
Fibrosis
Down-Regulation

Keywords

  • cardiac fibrosis
  • catecholamine
  • lysosomal enzymes
  • Mitochondrial enzymes
  • triterpenoid

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis

Cite this

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title = "Ursolic acid modulates MMPs, collagen-I, α-SMA, and TGF-β expression in isoproterenol-induced myocardial infarction in rats",
abstract = "In the present study, the modulatory effect of ursolic acid (UA) on cardiac fibrosis and mitochondrial and lysosomal enzymes activity in isoproterenol-induced myocardial infarction (MI) in rats were examined. Isoproterenol hydrochloride (ISO; 85 mg/kg body weight) was administered subcutaneously for first two consecutive days. ISO-induced MI in rats significantly decreased the activities of mitochondrial tricarboxylic acid cycle enzymes and respiratory chain enzymes while increased the activities of lysosomal glycohydrolases and cathepsins. The expression of matrix metalloproteinase 2 (MMP-2), MMP-9, collagen type I, α-smooth muscle actin (α-SMA), and transforming growth factor-β (TGF-β) were upregulated in ISO-induced MI in rats. UA administration to rats showed increased activities of mitochondrial tricarboxylic acid cycle enzymes and respiratory chain enzymes and decreased activities of lysosomal glycohydrolases and cathepsins in ISO-induced rats. Furthermore, expression of MMP-2, MMP-9, collagen type I, α-SMA, and TGF-β downregulated in UA-administered rats. Thus, our results demonstrate that UA has an anti-fibrotic effect and attenuates the mitochondrial and lysosomal dysfunction in ISO-induced MI in rats.",
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author = "T. Radhiga and Senthil Selvaraj and A. Sundaresan and Pugalendi, {K. V.}",
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T1 - Ursolic acid modulates MMPs, collagen-I, α-SMA, and TGF-β expression in isoproterenol-induced myocardial infarction in rats

AU - Radhiga, T.

AU - Selvaraj, Senthil

AU - Sundaresan, A.

AU - Pugalendi, K. V.

PY - 2019/1/1

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N2 - In the present study, the modulatory effect of ursolic acid (UA) on cardiac fibrosis and mitochondrial and lysosomal enzymes activity in isoproterenol-induced myocardial infarction (MI) in rats were examined. Isoproterenol hydrochloride (ISO; 85 mg/kg body weight) was administered subcutaneously for first two consecutive days. ISO-induced MI in rats significantly decreased the activities of mitochondrial tricarboxylic acid cycle enzymes and respiratory chain enzymes while increased the activities of lysosomal glycohydrolases and cathepsins. The expression of matrix metalloproteinase 2 (MMP-2), MMP-9, collagen type I, α-smooth muscle actin (α-SMA), and transforming growth factor-β (TGF-β) were upregulated in ISO-induced MI in rats. UA administration to rats showed increased activities of mitochondrial tricarboxylic acid cycle enzymes and respiratory chain enzymes and decreased activities of lysosomal glycohydrolases and cathepsins in ISO-induced rats. Furthermore, expression of MMP-2, MMP-9, collagen type I, α-SMA, and TGF-β downregulated in UA-administered rats. Thus, our results demonstrate that UA has an anti-fibrotic effect and attenuates the mitochondrial and lysosomal dysfunction in ISO-induced MI in rats.

AB - In the present study, the modulatory effect of ursolic acid (UA) on cardiac fibrosis and mitochondrial and lysosomal enzymes activity in isoproterenol-induced myocardial infarction (MI) in rats were examined. Isoproterenol hydrochloride (ISO; 85 mg/kg body weight) was administered subcutaneously for first two consecutive days. ISO-induced MI in rats significantly decreased the activities of mitochondrial tricarboxylic acid cycle enzymes and respiratory chain enzymes while increased the activities of lysosomal glycohydrolases and cathepsins. The expression of matrix metalloproteinase 2 (MMP-2), MMP-9, collagen type I, α-smooth muscle actin (α-SMA), and transforming growth factor-β (TGF-β) were upregulated in ISO-induced MI in rats. UA administration to rats showed increased activities of mitochondrial tricarboxylic acid cycle enzymes and respiratory chain enzymes and decreased activities of lysosomal glycohydrolases and cathepsins in ISO-induced rats. Furthermore, expression of MMP-2, MMP-9, collagen type I, α-SMA, and TGF-β downregulated in UA-administered rats. Thus, our results demonstrate that UA has an anti-fibrotic effect and attenuates the mitochondrial and lysosomal dysfunction in ISO-induced MI in rats.

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