Protective effects of saffron extract and its active constituent crocin against oxidative stress and spatial learning and memory deficits induced by chronic stress in rats

Eur J Pharmacol. 2011 Sep 30;667(1-3):222-9. doi: 10.1016/j.ejphar.2011.05.012. Epub 2011 May 18.


Although it is well established that chronic stress impairs spatial learning and memory, few studies have investigated possible ways to prevent its deleterious effects. Here, we investigated the effects of Crocus sativus L., commonly known as saffron, and its active constituent crocin on learning and memory loss and the induction of oxidative stress in the hippocampus by chronic stress. Rats were injected with saffron extract, crocin or vehicle over a period of 21 days while being exposed to chronic restraint stress (6 h/day). After this, they were trained and tested on a water-maze spatial memory task. They performed four trials per day for 5 consecutive days, and this was followed by a probe trial two days later. At the end of the behavioral testing, several parameters of oxidative stress in the hippocampus were measured. Treatment with saffron extract or crocin blocked the ability of chronic stress to impair spatial learning and memory retention. Relative to controls that received vehicle, stressed animals that received saffron extract or crocin had significantly higher levels of lipid peroxidation products, significantly higher activities of antioxidant enzymes including glutathione peroxidase, glutathione reductase and superoxide dismutase and significantly lower total antioxidant reactivity capacity. Finally, crocin significantly decreased plasma levels of corticosterone, as measured after the end of stress. These observations indicate that saffron and its active constituent crocin can prevent the impairment of learning and memory as well as the oxidative stress damage to the hippocampus induced by chronic stress. Thus, using these substances may be useful in pharmacological alleviation of cognitive deficits.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Antioxidants / metabolism
  • Carotenoids / administration & dosage
  • Carotenoids / pharmacology*
  • Corticosterone / blood
  • Crocus / chemistry*
  • Glutathione Peroxidase / metabolism
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Male
  • Memory / drug effects*
  • Memory / physiology
  • Oxidative Stress / drug effects*
  • Plant Extracts / administration & dosage
  • Plant Extracts / pharmacology*
  • Rats
  • Rats, Wistar
  • Spatial Behavior / drug effects*
  • Spatial Behavior / physiology
  • Stress, Psychological / blood
  • Stress, Psychological / enzymology
  • Stress, Psychological / metabolism
  • Stress, Psychological / physiopathology*
  • Thiobarbituric Acid Reactive Substances / metabolism
  • Time Factors


  • Antioxidants
  • Plant Extracts
  • Thiobarbituric Acid Reactive Substances
  • Carotenoids
  • crocin
  • Glutathione Peroxidase
  • Corticosterone