Hesperidin-mediated expression of Nrf2 and upregulation of antioxidant status in senescent rat heart

J Pharm Pharmacol. 2012 Oct;64(10):1472-82. doi: 10.1111/j.2042-7158.2012.01512.x. Epub 2012 May 9.


Objectives: Oxidative stress is recognized as a key element responsible for the development of age-related pathologies. A declining endogenous defence system during senescence dictates the need for supplementation with exogenous antioxidants through diet. Hesperidin is a naturally occurring flavonone present in citrus fruits and has been shown to have many biological properties, including antioxidant activity. We investigated whether hesperidin supplementation could be valuable in protecting cardiac tissue of aged rats against age-related increase in oxidative stress, as well as the mechanism by which it can boost the antioxidant status of the cell.

Methods: The activity of antioxidant enzymes, mRNA expression of Nrf2, protein levels of superoxide dismutase and catalase were measured using standard protocols.

Key findings: Hesperidin treatment effectively protected aged rat heart by increasing the activity of enzymic antioxidants. Hesperidin upregulated the protein levels of nuclear factor erythroid 2-related factor 2, which is responsible for maintaining the antioxidant status of the cell.

Conclusions: Hesperidin could be useful in protecting cardiomyocytes against age-related increase in oxidative stress mediated by Nrf2 upregulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Aging
  • Animals
  • Antioxidants / metabolism
  • Antioxidants / pharmacology*
  • Catalase / metabolism
  • Heart / drug effects
  • Hesperidin / pharmacology*
  • Male
  • Myocardium / metabolism
  • NF-E2-Related Factor 2 / genetics*
  • Oxidative Stress / drug effects
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Wistar
  • Superoxide Dismutase / metabolism
  • Up-Regulation / drug effects*


  • Antioxidants
  • NF-E2-Related Factor 2
  • Nfe2l2 protein, rat
  • RNA, Messenger
  • Hesperidin
  • Catalase
  • Superoxide Dismutase