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Cardiovascular Drugs and Therapy

, Volume 32, Issue 2, pp 147–163 | Cite as

Pterostilbene Decreases Cardiac Oxidative Stress and Inflammation via Activation of AMPK/Nrf2/HO-1 Pathway in Fructose-Fed Diabetic Rats

  • Ramoji Kosuru
  • Vidya Kandula
  • Uddipak Rai
  • Swati Prakash
  • Zhengyuan Xia
  • Sanjay Singh
ORIGINAL ARTICLE

Abstract

Purpose

Oxidative stress has a pivotal role in the pathogenesis of diabetes-associated cardiovascular problems, which has remained a primary cause of the increased morbidity and mortality in diabetic patients. It is of paramount importance to prevent the diabetes-associated cardiac complications by reducing oxidative stress with the help of nutritional or pharmacological agents. Pterostilbene (PT), the primary antioxidant in blueberries, has recently gained attention for its promising health benefits in metabolic and cardiac diseases. However, the mechanism whereby PT reduces diabetic cardiac complications is currently unknown.

Methods

Sprague-Dawley rats were fed with 65% fructose diet with or without PT (20 mg kg−1 day−1) for 8 weeks. Heart rate and blood pressure were measured by tail-cuff apparatus. Real-time PCR and western blot experiments were executed to quantify the expression levels of mRNA and protein, respectively.

Results

Fructose-fed rats demonstrated cardiac hypertrophy, hypertension, enhanced myocardial oxidative stress, inflammation and increased NF-κB expression. Administration of PT significantly decreased cardiac hypertrophy, hypertension, oxidative stress, inflammation, NF-κB expression and NLRP3 inflammasome. We demonstrated that PT improved mitochondrial biogenesis as evidenced by increased protein expression of PGC-1α, complex III and complex V in fructose-fed diabetic rats. Further, PT increased protein expressions of AMPK, Nrf2, HO-1 in cardiac tissues, which may account for the prevention of cardiac oxidative stress and inflammation in fructose-fed rats.

Conclusions

Collectively, PT reduced cardiac oxidative stress and inflammation in diabetic rats through stimulation of AMPK/Nrf2/HO-1 signalling.

Keywords

AMPK Pterostilbene Nrf2 HO-1 Oxidative stress Inflammation NLRP3 inflammasome 

Abbreviations

PT

Pterostilbene

AMPK

5′ adenosine monophosphate-activated protein kinase

SOD

Superoxide dismutase

GSH

Reduced glutathione

GPx

Glutathione peroxidase

ROS

Reactive oxygen species

TBARS

Thiobarbituric acid reactive substances

HO-1

Heme-oxygenase

NF-κB

Nuclear factor- κB

IL

Interleukin

TNF-α

Tumour necrosis factor-α

LDH

Lactate dehydrogenase

CK-MB

Creatine kinase-MB

AST

Aspartate aminotransferase

MAP

Mean arterial pressure

ELISA

Enzyme-linked immunosorbent assay

PCR

Polymerase chain reaction

PGC-1α

Peroxisome proliferator-activated receptor gamma coactivator

Nrf2

Nuclear factor erythroid 2–related factor 2

GAPDH

Glyceraldehyde 3-phosphate dehydrogenase

C

Control

D

Fructose-fed diabetic

NLRP3

Nucleotide-binding oligomerisation domain-like receptor (NLR) protein 3

ASC

The adapter protein apoptosis-associated speck-like protein containing caspase recruitment domain

TLR4

Toll-like receptor 4

CC

Compound C

TXNIP

Thioredoxin-interacting protein.

Notes

Acknowledgements

Ramoji Kosuru was supported by the Indian Institute of Technology (Banaras Hindu University), Varanasi for providing Teaching Assistantship funded by Ministry of Human Resource Development, Government of India. We gratefully acknowledge the Sami Labs Limited, Bangalore, India, for providing pterostilbene as a generous gift sample.

Compliance with Ethical Standards

Conflicts of Interest

The authors declare that they have no conflict of interest.

Ethical Approval

The current investigation was performed in agreement with the principles of the Guide for the Care and Use of Laboratory Animals, published by the National Institutes of Health (NIH publication no. 86–23, revised 1996), and the experiments were approved by the Institutional Animal Ethical Committee of Institute of Medical Sciences (IMS), Banaras Hindu University (BHU), Varanasi, India.

Informed Consent

This study was not a clinical research and therefore consent for participate was not needed.

Consent for Publication

All authors have approved the submission for publication of the work.

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Authors and Affiliations

  1. 1.Department of Pharmaceutical Engineering & TechnologyIndian Institute of Technology (Banaras Hindu University)VaranasiIndia
  2. 2.Department of Anaesthesiology, Li Ka Shing Faculty of MedicineThe University of Hong KongPok Fu LamHong Kong

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