Neuroprotective effect of Crocus sativus against cerebral ischemia in rats

  • Rehab F. Abdel-RahmanEmail author
  • Sally A. El Awdan
  • Rehab R. Hegazy
  • Dina F. Mansour
  • H. A. Ogaly
  • Marwan Abdelbaset
Original Article


The present study aimed to investigate the role of vascular endothelial growth factor (VEGF) in the neuroprotective effect of Crocus sativus (saffron) against cerebral ischemia/reperfusion injury (I/R) in rats. Four groups of a total forty I/R rats with 60-min occlusion followed by 48 h reperfusion or sham surgery were used. The sham and left-brain I/R control groups where treated with normal saline. The rats of the other two groups received saffron extract (100 or 200 mg/kg, ip, respectively) for 3 successive weeks prior to left-brain I/R. Other four doses of saffron extract were received by the rats of the last 2 groups 60 min prior to operation, during the surgery, and on days 1 and 2 following reperfusion. I/R group showed marked neurobehavioral, neurochemical and histopathological alterations. The results revealed a significant reduction in neurological deficit scores in the saffron-treated rats at both doses. Saffron significantly attenuated lipid peroxidation, decreased NO and brain natriuretic peptide (BNP) contents in I/R-brain tissue. On the other hand, saffron reversed the depletion of GSH in the injured brain. Moreover, saffron treatment evidently reduced apoptosis as revealed by a decrease in caspase-3 and Bax protein expression with a marked decrease in the apoptotic neuronal cells compared to I/R group. In addition, saffron administration effectively upregulated the expression of VEGF in I/R-brain tissue. In conclusion, saffron treatment offers significant neuroprotection against I/R damage possibly through diminishing oxidative stress and apoptosis and enhancement of VEGF.


Cerebral Ischemia/reperfusion Crocus sativus VEGF Caspase-3 Rats 



The authors would like to thank Dr. Reham M. Abd-Elsalam, Department of Pathology, Faculty of Veterinary Medicine, Cairo University, Egypt for performing the histopathology and the immunohistochemical investigations in the present study. Authors are Grateful to Dr. Ahmed H. El-Desoky and Dr. Rehab A. Hussein, Department of Pharmacognosy, National Research Centre, Egypt for LC-MS analysis of saffron extract.

Author contribution

RA and SA conceived and designed research. RA, SA, RH, DM, HO and MA conducted experiments. MA, RA and SA analyzed data. RA and HO wrote the manuscript. All authors read and approved the manuscript.

Funding information

The authors are thankful to the National Research Centre-Egypt (NRC) for funding the research project no. P100516.

Compliance with ethical standards

Conflict of interest

The authors have declared that no conflict of interests exists.


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Authors and Affiliations

  1. 1.Pharmacology DepartmentNational Research CentreGizaEgypt
  2. 2.Chemistry Department, College of ScienceKing Khalid UniversityAbhaSaudi Arabia
  3. 3.Biochemistry Department, Faculty of Veterinary MedicineCairo UniversityGizaEgypt

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