title: Protective effect of crocin against cerebral ischemia in a dose-dependent manner in a rat model of ischemic stroke.
abstract: BACKGROUND
  Crocin is a water-soluble carotenoid isolated from the Crocus sativus L (saffron) stigma. It has previously been reported that it has protective effects against renal, cardiac, and global cerebral ischemic injury. However its therapeutic effects remain to be clarified regarding ischemic reperfusion injuries, brain edema, and activity of antioxidant enzymes in a transient model of focal cerebral ischemia.
  
  
  METHODS
  Transient focal cerebral ischemia was induced by 60-minute middle cerebral artery occlusion (MCAO), followed by 23-hour reperfusion. Crocin at doses of 15, 30, 60, and 120 mg/kg intraperitoneally were injected at the start of ischemia. Infarct volume and neurologic outcome were evaluated 24 hours after MCAO. For the therapeutic time window measurement, crocin (60 mg/kg) was given 1, 3, and 6 hours after ischemia; 24 hours later brain edema and antioxidant enzyme activity were assessed.
  
  
  RESULTS
  The results indicated that treatment with crocin at doses of 30, 60, and 120 mg/kg significantly decreased infarct volume by 64%, 74%, and 73%, respectively. Administration of crocin (60 mg/kg) 1 hour before, at the start, or 1 hour after ischemia reduced brain edema by 48%, 52%, and 51%, respectively. Moreover, crocin (60 mg/kg) significantly reduced malondialdehyde (MDA) content and increased activity of superoxide dismutase (SOD) and glutathione peroxidase (GPx) in the ischemic cortex (P< .001).
  
  
  CONCLUSIONS
  Our findings indicate that crocin has protective effects against ischemic reperfusion injury and cerebral edema in a rat model of stroke. These effects of crocin may have been exerted primarily by suppression of the production of free radicals and increased antioxidant enzyme activity.
authors.affiliation: Laboratory of Cerebrovascular Research, Research Center and Department of Physiology, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran. Electronic address: ab.vakili@yahoo.com.
authors.forename: Abedin
authors.initials: A
authors.lastname: Vakili
authors.affiliation: Laboratory of Cerebrovascular Research, Research Center and Department of Physiology, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran.
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Einali
authors.affiliation: Department of Biochemistry, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran.
authors.forename: Ahmad Reza
authors.initials: AR
authors.lastname: Bandegi
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001522:Behavior, Animal / Q000187:drug effects; D001834:Body Water / Q000378:metabolism; D001921:Brain / Q000201:enzymology / Q000473:pathology; D001929:Brain Edema / Q000188:drug therapy; D002545:Brain Ischemia / Q000517:prevention & control*; D002338:Carotenoids / Q000627:therapeutic use*; D002544:Cerebral Infarction / Q000473:pathology / Q000517:prevention & control; D002560:Cerebrovascular Circulation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005979:Glutathione Peroxidase / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020521:Stroke / Q000517:prevention & control*; D013482:Superoxide Dismutase / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D000975:Antioxidants; D002338:Carotenoids; D008315:Malondialdehyde; C029036:crocin; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase