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Cardiovascular Toxicology

, Volume 19, Issue 1, pp 23–35 | Cite as

Beneficial Effect of Silymarin in Pressure Overload Induced Experimental Cardiac Hypertrophy

  • Basant Sharma
  • Udit Chaube
  • Bhoomika M. PatelEmail author
Article
  • 55 Downloads

Abstract

The present investigation was undertaken to study the effect of silymarin on cardiac hypertrophy induced by partial abdominal aortic constriction (PAAC) in Wistar rats. Silymarin was administered for 9 weeks at the end of which we evaluated hypertrophic, hemodynamic, non-specific cardiac markers, oxidative stress parameters, and determined mitochondrial DNA concentration. Hypertrophic control animals exhibited cardiac hypertrophy, altered hemodynamics, oxidative stress, and decreased mitochondrial DNA (mtDNA) concentration. Treatment with silymarin prevented cardiac hypertrophy, improved hemodynamic functions, prevented oxidative stress and increased mitochondrial DNA concentration. Docking studies revealed that silymarin produces maximum docking score with mitogen-activated protein kinases (MAPK) p38 as compared to other relevant proteins docked. Moreover, PAAC-control rats exhibited significantly increased expression of MAPK p38β mRNA levels which were significantly decreased by the treatment of silymarin. Our data suggest that silymarin produces beneficial effects on cardiac hypertrophy which are likely to be mediated through inhibition of MAPK p38β.

Keywords

Partial abdominal aortic constriction (PAAC) Cardiac hypertrophy Silymarin MAPK p38 β Mitochondrial DNA 

Abbreviations

MABP

Mean arterial blood pressure

MAPK

Mitogen-activated protein kinases

MAP3K5

Mitogen-activated protein kinase kinase kinase 5

MKK3/6

Mitogen-activated protein kinase kinase 3/6

PAAC

Partial abdominal aortic constriction

CON

Sham control

COS50

Sham control animals treated with silymarin (50 mg/kg/day, p.o)

COS100

Sham control animals treated with silymarin (100 mg/kg/day, p.o)

HYP

Hypertrophic control

HYS50

Hypertrophic animals treated with silymarin (50 mg/kg/day, p.o)

HYS100

Hypertrophic animals treated with silymarin (100 mg/kg/day, p.o)

CRP

C-reactive protein

LDH

Lactate de-hydrogenase

CK

Creatinine kinase

dp/dtmax

Rate of pressure development

dp/dtmin

Rate of pressure decay

CHI

Cardiac hypertrophic index

LVHI

Left ventricular hypertrophic index

LVW/RVW

Left ventricular weight-to-right ventricular weight ratio

HW/BW

Heart weight-to-body weight ratio

MDA

Malondialdehyde

GSH

Reduced glutathione

SOD

Superoxide dismutase

mtDNA

Mitochondrial DNA

GOLD

Genetic optimization for ligand docking

JNK1/2/3

c-Jun NH2 terminal kinases

ERK1/2

Extracellular signal-regulated kinases

HMG-CoA

3-Hydroxy-3-methylglutaryl-coenzyme

PDB

Protein data bank

Notes

Acknowledgements

The authors acknowledge Dr. Hardik Bhatt, Associate Professor, Department of Chemistry, Institute of Pharmacy, Nirma University for rendering required help in the docking studies.

Compliance with Ethical Standards

Conflict of interest

The authors declare no conflict of interests.

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Authors and Affiliations

  1. 1.Institute of PharmacyNirma UniversityAhmedabadIndia

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