Suppressive effect of quercetin on acute stress-induced hypothalamic-pituitary-adrenal axis response in Wistar rats

J Nutr Biochem. 2010 May;21(5):374-80. doi: 10.1016/j.jnutbio.2009.01.008. Epub 2009 May 7.


The flavonoid quercetin is considered to have beneficial effects on human health. We recently have shown that quercetin-enriched foods reduced the duration of immobility time in a rat forced swimming test, indicating that dietary quercetin is promising as an antidepressant-like factor, whereas its mechanism of action is poorly understood. The aim of this study is to investigate the effects of quercetin on water immersion-restraint (WIR), stress-induced hypothalamic-pituitary-adrenal (HPA) axis activation, which is a major component of stress response and plays an important role in the pathology of depression. Quercetin administration to rats significantly suppressed WIR stress-induced increase of plasma corticosterone and adrenocorticotropic hormone levels as well as the mRNA expression of corticotropin-releasing factor (CRF) in the hypothalamic region. In addition, quercetin modulated the DNA binding activities of glucocorticoid receptor and phosphorylated cyclic adenosine 3',5'-monophosphate (cAMP) response element binding protein as well as the phosphorylation of extracellular signal-regulated kinase 1/2 in the hypothalamic region, all of which are known to regulate the expression of CRF mRNA. Taken together, these results suggest that dietary quercetin attenuates the HPA axis activation by the suppression of the CRF mRNA expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenocorticotropic Hormone / blood
  • Animals
  • Antidepressive Agents / administration & dosage*
  • Corticosterone / blood
  • Corticotropin-Releasing Hormone / genetics
  • Corticotropin-Releasing Hormone / metabolism
  • Cyclic AMP Response Element-Binding Protein / metabolism
  • DNA-Binding Proteins / metabolism
  • Depression / diet therapy
  • Depression / prevention & control
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Hypothalamo-Hypophyseal System / metabolism*
  • Immersion / adverse effects
  • Male
  • Phosphorylation
  • Pituitary-Adrenal System / metabolism*
  • Protein Processing, Post-Translational
  • Quercetin / administration & dosage*
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Wistar
  • Receptors, Glucocorticoid / metabolism
  • Restraint, Physical
  • Stress, Psychological / blood
  • Stress, Psychological / diet therapy
  • Stress, Psychological / prevention & control*
  • Time Factors


  • Antidepressive Agents
  • Cyclic AMP Response Element-Binding Protein
  • DNA-Binding Proteins
  • RNA, Messenger
  • Receptors, Glucocorticoid
  • Adrenocorticotropic Hormone
  • Corticotropin-Releasing Hormone
  • Quercetin
  • Extracellular Signal-Regulated MAP Kinases
  • Corticosterone