Cardioprotective Effect of Saffron Extract and Safranal in Isoproterenol-Induced Myocardial Infarction in Wistar Rats

Document Type: Original Article

Authors

1 Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

2 Department of Biochemistry and Nutrition, Faculty of Medicine, Mashhad, Iran

3 Department of Pathology, Imam Reza Hospital, Faculty of Medicine, Mashhad, Iran

4 Pharmaceutical Research Center, Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

Abstract

Objective(s):This study was designed to evaluate the cardioprotective effect of Crocus sativus L. (saffron)aqueous extract and safranal, the major constituent of the essential oil of saffron, on lipid peroxidation, biochemical parameters and histopathological findings in isoproterenol (ISO)-induced myocardial infarction in Wistar rats.
Materials and Methods:The saffron extract (20, 40, 80 and 160 mg/kg/day IP) or control were administered for 9 days along with ISO (85 mg/kg, SC, at 24 hr interval) on 8th and 9th day in rats. Activities of creatine kinase-muscle, brain (CK-MB) and lactate dehydrogenase (LDH) were measured using standard commercial kits. The level of malondialdehyde in heart tissue was estimated with thiobarbituric acid reactive species test. For histopathological examination, hematoxylin and eosin (H&E) staining was used.
Results:ISO administration induced a statistically significant increase          (P< 0.001) in serum LDH and CK-MB and a significant increase  (P< 0.001) in the levels of thiobarbituric acid reactive substances (TBARs) in the heart as compared to vehicle control rats. Saffron pretreatment (20, 40, 80 and 160 mg/kg IP) or safranal pretreatment (0.025, 0.050, 0.075 ml/kg IP) for 8 days, significantly decreased (P< 0.001) the serum LDH and CK-MB and myocardial lipid peroxidation as compared to ISO- induced rats. Histological findings of the heart sections confirmed myocardial injury with ISO administration and preserved nearly normal tissue architecture with saffron or safranal pretreatment.
Conclusion:Saffron and safranal may have cardioprotective effect in ISO-inducedmyocardial infarction through modulation of oxidative stress in such a way that they maintain the redox status of the cell.

Keywords


1. Kumar JS, Menon VP. Changes in levels of lipid peroxides and activity of superoxide dismutase and catalase in diabetes associated with myocardial infarction. Indian J Exp Biol1992; 30:122-127.

2. De Biase L, Pinatelli P, Lenti L, Tocci G, Piccioni F, Riondino S, et al. Enhanced TNF alpha and oxidative stress in patients with heart failure: effect of TNF alpha on platelet O2- production. Thromb Haemost2003; 90: 317-325.

3. Rajadurai M, Prince PS. Preventive effect of naringin on cardiac markers, electrocardiographic patterns and lysosomal hydrolases in normal and isoproterenol-induced myocardial infarction in Wistar rats. Toxicology 2007; 230:178-188.

4. Nakamura T, Nishi H, Kokusenya Y, Hirota K, Miura Y. Mechanism of antioxidative activity of fluvastatin-determination of the active position. Chem Pharm Bull2000; 48:235-237.

5. Rathore N, John S, Kale M, Bhatnagar D. Lipid peroxidation and antioxidant enzymes in isoproterenol induced oxidative stress in rat tissues. Pharmacol Res1998; 38:297-303.

6. Zhou R, Xu Q, Zheng P, Yan L, Zheng J, Dai G.  Cardioprotective effect of fluvastatin on isoproterenol-induced myocardial infarction in rat. Eur J Pharmacol2008; 586:244-250.

7. Gupta SK, Mohanty I, Talwar KK, Dinda A, Joshi S, Bansal P, et al. Cardioprotection from ischemia and reperfusion injury by Withania somnifera: a hemodynamic, biochemical and histopathological assessment. Mol Cell Biochem2004; 260:39-47.

8. Devika PT, Prince PS. Protective effect of (-)-epigallocatechin-gallate (EGCG) on lipid peroxide metabolism in isoproterenol induced myocardial infarction in male Wistar rats: a histopathological study. Biomed Pharmacother2008; 62:701-708.

9. Rios JL, Recio MC,Giner RM, Máñez S: An update review of saffron and its active constituents. Phytother Res1996; 10: 189-193.

10. Abdullaev FI, Espinosa-Aguirre JJ. Biomedical properties of saffron and its potential use in cancer therapy and chemoprevention trials. Cancer Detect Prev 2004; 28:426-432.

11. Assimopoulou AN, Sinakos Z, Papageorgiou VP. Radical scavenging activity of Crocus sativus L. extract and its bioactive constituents. Phytother Res2005; 19:997-1000.

12. Hosseinzadeh H, Karimi G, Niapoor M. Antidepressant effects of Crocus sativus stigma extracts and its constituents, crocin and safranal, in mice. J Med Plants2004; 3:48-58.

13. Hosseinzadeh H, Talebzadeh F. Anticonvulsant evaluation of safranal and crocin from Crocus sativus in mice. Fitoterapia 2005; 76:722-724.

14. Hosseinzadeh H, Ghenaati J. Evaluation of the antitussive effect of stigma and petals of saffron (Crocus sativus) and its components, safranal and crocin in guinea pigs. Fitoterapia2006; 77: 446-448.

15. Hosseinzadeh H, Ziaee T, Sadeghi A. The effect of saffron, Crocus sativus stigma, extract and its constituents, safranal and crocin on sexual behaviors in normal male rats. Phytomedicine2008; 15: 491-495.

16. Hosseinzadeh H, Noraei NB: Anxiolytic and hypnotic effect of Crocus sativus aqueous extract and its constituents, crocin and safranal, in mice. Phytother Res 2009; 23:768-774.

17.  Nemati H, Boskabady MH, Ahmadzadef Vostakolaei H. Stimulatory effect of Crocus sativus (saffron) on beta2-adrenoceptors of guinea pig tracheal chains. Phytomedicine 2008; 15:1038-45.

18.  Boskabady MH, Aslani MR: Relaxant effect of Crocus sativus (saffron) on guinea-pig tracheal chains and its possible mechanisms. J Pharm Pharmacol 2006; 58:1385-1390.

19. Hosseinzadeh H, Sadeghnia HR, Ziaee T, Danaee A. Protective effect of aqueous saffron extract (Crocus sativus L.) and crocin, its active constituent, on renal ischemia-reperfusion-induced oxidative damage in rats. J Pharm Pharm Sci2005; 8: 387-393.

20. Hosseinzadeh H, Sadeghnia HR: Safranal, a constituent of Crocus sativus (saffron), attenuated cerebral ischemia induced oxidative damage in rat hippocampus. J Pharm Pharm Sci2005; 8: 394-399.

21. Hosseinzadeh H, Modaghegh MH, Saffari Z. Crocus sativus L. (saffron) extract and its active constituents (crocin and safranal) on ischemia-reperfusion in rat skeletal muscle.EvidBased Complement Alternat Med 2009; 6:343-350.

22. Assimopoulou AN, Sinakos Z, Papageorgiou VP. Radical scavenging activity of Crocus sativus L. extract and its bioactive constituents. Phytother Res2005; 19: 997-1000.

23. Hosseinzadeh H, Shamsaie F,Mehri S. Antioxidant activity of aqueous and ethanolic extracts of Crocus sativus L. stigma and its bioactive constituents cracin and Safranal. Pharma cog Mag  2010; 5:419-424.

24. Nazam Ansari M, Bandari U, Philli KK. Protective role of curcumin in myocardial oxidative damage induced by isoproterenol in rats. Hum Exp Toxicolo 2007; 26:933-938.

25. Sabeena Farvin KH, Anandan R, Kumar SH, Shiny KS, Sankar TV, Thankappan TK. Effect of squalene on tissue defense system in isoproterenol-induced myocardial infarction in rats. Pharmacol Res2004; 50:231-236.

26. Rajadurai M, Stanely Mainzen Prince P: Preventive effect of naringin on lipid peroxides and antioxidants in isoproterenol-induced cardiotoxicity in Wistar rats: Biochemical and histopathological evidences. Toxicology2006; 228: 259-268.

27. Zhou B, Wu LJ, Tashiro S, Onodera S, Uchiumi F, Ikejima T. Silibinin protects rat cardiac myocyte from isoproterenol-induced DNA damage independent on regulation of cell cycle. Biol Pharm Bull2006; 29: 1900-1905.

28. Hosseinzadeh H, Sadeghnia HR. Safranal, a constituent of Crocus sativus (saffron), attenuated cerebral ischemia induced oxidative damage in rat hippocampus.J Pharm Pharm Sci 2005; 8:394-399.

29. Sawyer DB, Siwik DA, Xiao L, Pimentel DR, Singh K, Colucci WS. Role of oxidative stress in myocardial hypertrophy and failure. J Mol Cell Cardiol2002; 34:379-388.