Protective effects of Echium amoenum Fisch. and C.A. Mey. against cerebral ischemia in the rats

Authors

1 Department of Pharmacology and Toxicology, School of Pharmacy and Pharmaceutical Sciences, Isfahan Pharmaceutical Sciences Research Center, Isfahan, Iran

2 Department of Physiology, Anatomical Research Center, Kashan University of Medical Science, Kashan, Iran

3 Department of Pharmacognosy, School of Pharmacy and Pharmaceutical Sciences, Isfahan Pharmaceutical Sciences Research Center, Isfahan, Iran

4 Physiology Research Center, Kashan University of Medical Science, Kashan, Iran

Abstract

Background: This study was designed to evaluate the protective effect of Echium amoenum total anthocyanin extract (ETAE) on partial/transient cerebral ischemia in the rats.
Materials and Methods: Rats received ETAE (50, 100 and 200 mg/kg, i.p.) 30 min before the induction of cerebral ischemia. Cerebral ischemia was induced by bilateral common carotid arteries occlusion (BCCAO) for 30 min, followed by 72 h reperfusion. The neurological deficit, brain performance, and sensory motor function were assessed 48 h and 72 h after surgery. After sacrification, the brains were evaluated for myeloperoxidase (MPO) activity and histopathological changes.
Results: Our results showed that motor function significantly decreased in ischemia/reperfusion (I/R) group as compared to the sham group. Histopathological analysis exhibited the shrinkage and atrophy of the neurons in I/R group. ETAE at the dose of 200 mg/kg improved spontaneous activity and memory induced by cerebral ischemia compared to the control group and also decreased brain MPO activity following cerebral ischemia. However, it could not affect the ability to climbing, body proprioception, vibrissae touch and brain water content. In addition, pretreatment with ETAE at higher doses significantly reduced ischemia-induced neuronal loss of the brain.
Conclusion: The anthocyanin rich fraction from E. amoenum was found to have protective effects against some brain damages postischemic reperfusion . However, further researches are required for investigating the exact mechanisms of the effect of this plant in the prevention of cerebral ischemia in human.

Keywords

1.
of population health data. Lancet 2006;367:1747-57.  Back to cited text no. 1
    
2.
Bernard SA, Gray TW, Buist MD, Jones BM, Silvester W, Gutteridge G, et al. Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia. N Engl J Med 2002;346:557-63.  Back to cited text no. 2
    
3.
Hypothermia after Cardiac Arrest Study Group. Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. N Engl J Med 2002;346:549-56.  Back to cited text no. 3
    
4.
Salazar JD, Wityk RJ, Grega MA, Borowicz LM, Doty JR, Petrofski JA, et al. Stroke after cardiac surgery: Short- and long-term outcomes. Ann Thorac Surg 2001;72:1195-201.  Back to cited text no. 4
    
5.
Nussmeier NA. A review of risk factors for adverse neurologic outcome after cardiac surgery. J Extra Corpor Technol 2002;34:4-10.  Back to cited text no. 5
    
6.
Murkin JM. Etiology and incidence of brain dysfunction after cardiac surgery. J Cardiothorac Vasc Anesth 1999;13:12-7.  Back to cited text no. 6
    
7.
Llinas R, Barbut D, Caplan LR. Neurologic complications of cardiac surgery. Prog Cardiovasc Dis 2000;43:101-12.  Back to cited text no. 7
    
8.
Kleinschnitz C, Stoll G, Bendszus M, Schuh K, Pauer HU, Burfeind P, et al. Targeting coagulation factor XII provides protection from pathological thrombosis in cerebral ischemia without interfering with hemostasis. J Exp Med 2006;203:513-8.  Back to cited text no. 8
    
9.
Kleinschnitz C, Pozgajova M, Pham M, Bendszus M, Nieswandt B, Stoll G. Targeting platelets in acute experimental stroke: Impact of glycoprotein Ib, VI, and IIb/IIIa blockade on infarct size, functional outcome, and intracranial bleeding. Circulation 2007;115:2323-30.  Back to cited text no. 9
    
10.
Kleinschnitz C, De Meyer SF, Schwarz T, Austinat M, Vanhoorelbeke K, Nieswandt B, et al. Deficiency of von Willebrand factor protects mice from ischemic stroke. Blood 2009;113:3600-3.  Back to cited text no. 10
    
11.
Stoll G, Kleinschnitz C, Nieswandt B. Molecular mechanisms of thrombus formation in ischemic stroke: Novel insights and targets for treatment. Blood 2008;112:3555-62.  Back to cited text no. 11
    
12.
Garthwaite J, Charles SL, Chess-Williams R. Endothelium-derived relaxing factor release on activation of NMDA receptors suggests role as intercellular messenger in the brain. Nature 1988;336:385-8.  Back to cited text no. 12
    
13.
Vincent SR. Nitric oxide: A radical neurotransmitter in the central nervous system. Prog Neurobiol 1994;42:129-60.  Back to cited text no. 13
    
14.
Bredt DS, Snyder SH. Isolation of nitric oxide synthetase, a calmodulin- requiring enzyme. Proc Natl Acad Sci U S A 1990;87:682-5.  Back to cited text no. 14
    
15.
Knowles RG, Moncada S. Nitric oxide synthases in mammals. Biochem J 1994;298 (Pt 2):249-58.  Back to cited text no. 15
    
16.
Lo EH, Moskowitz MA, Jacobs TP. Exciting, radical, suicidal: How brain cells die after stroke. Stroke 2005;36:189-92.  Back to cited text no. 16
    
17.
Mukherjee PK, Ahamed KF, Kumar V, Mukherjee K, Houghton PJ. Protective effect of biflavones from Araucaria bidwillii Hook in rat cerebral ischemia/reperfusion induced oxidative stress. Behav Brain Res 2007;178:221-8.  Back to cited text no. 17
    
18.
Hooper D. Useful Plants and Drugs of Iran and Iraq. Chicago, Ill, USA: Field Museum of Natural History; 1937.  Back to cited text no. 18
    
19.
Abolhassani M. Antibacterial effect of borage (Echium amoenum) on Staphylococcus aureus. Braz J Infect Dis 2004;8:382-5.  Back to cited text no. 19
    
20.
Ranjbar A, Khorami S, Safarabadi M, Shahmoradi A, Malekirad AA, Vakilian K, et al. Antioxidant activity of Iranian Echium amoenum Fisch and C.A. Mey flower decoction in humans: A cross-sectional Before/After Clinical Trial. Evid Based Complement Alternat Med 2006;3:469-73.  Back to cited text no. 20
    
21.
Heidari MR, Azad EM, Mehrabani M. Evaluation of the analgesic effect of Echium amoenum Fisch and C.A. Mey. extract in mice: Possible mechanism involved. J Ethnopharmacol 2006;103:345-9.  Back to cited text no. 21
    
22.
Rabbani M, Sajjadi SE, Vaseghi G, Jafarian A. Anxiolytic effects of Echium amoenum on the elevated plus-maze model of anxiety in mice. Fitoterapia 2004;75:457-64.  Back to cited text no. 22
    
23.
Sayyah M, Sayyah M, Kamalinejad M. A preliminary randomized double blind clinical trial on the efficacy of aqueous extract of Echium amoenum in the treatment of mild to moderate major depression. Prog Neuropsychopharmacol Biol Psychiatry 2006;30:166-9.  Back to cited text no. 23
    
24.
Amirghofran Z, Azadbakht M, Keshavarzi F. Echium amoenum stimulate of lymphocyte proliferation and inhibit of humoral antibody synthesis. Iran J Basic Med Sci 2000;25:119-24.  Back to cited text no. 24
    
25.
Sayyah M, Boostani H, Pakseresht S, Malaieri A. Efficacy of aqueous extract of Echium amoenum in treatment of obsessive-compulsive disorder. Prog Neuropsychopharmacol Biol Psychiatry 2009;33:1513-6.  Back to cited text no. 25
    
26.
Mehrabani M, Ghassemi N, Sajjadi E, Ghannadi A, Shams-Ardakani M. Main phenolic compound of petals of Echium amoenum Fisch. and C.A. Mey., A famous medicinal plant of Iran. Daru J Pharm Sci 2005;13:65-9.  Back to cited text no. 26
    
27.
Muñoz-Espada AC, Watkins BA. Cyanidin attenuates PGE2 production and cyclooxygenase-2 expression in LNCaP human prostate cancer cells. J Nutr Biochem 2006;17:589-96.  Back to cited text no. 27
    
28.
Min J, Yu SW, Baek SH, Nair KM, Bae ON, Bhatt A, et al. Neuroprotective effect of cyanidin-3-O-glucoside anthocyanin in mice with focal cerebral ischemia. Neurosci Lett 2011;500:157-61.  Back to cited text no. 28
    
29.
Hwang MK, Kang NJ, Heo YS, Lee KW, Lee HJ. Fyn kinase is a direct molecular target of delphinidin for the inhibition of cyclooxygenase-2 expression induced by tumor necrosis factor-alpha. Biochem Pharmacol 2009;77:1213-22.  Back to cited text no. 29
    
30.
Gülçin I, Berashvili D, Gepdiremen A. Antiradical and antioxidant activity of total anthocyanins from Perilla pankinensis decne. J Ethnopharmacol 2005;101:287-93.  Back to cited text no. 30
    
31.
Wrolstad R. Current Protocols in Food Analytical Chemistry. New York, NY, USA: John Wiley and Sons; 2000.  Back to cited text no. 31
    
32.
Di Giacomo C, Acquaviva R, Santangelo R, Sorrenti V, Vanella L, Li Volti G, et al. Effect of treatment with cyanidin-3-O-ß-D-glucoside on rat ischemic/reperfusion brain damage. Evid Based Complement Alternat Med 2012;2012:285750.  Back to cited text no. 32
    
33.
Bradley PP, Priebat DA, Christensen RD, Rothstein G. Measurement of cutaneous inflammation: Estimation of neutrophil content with an enzyme marker. J Invest Dermatol 1982;78:206-9.  Back to cited text no. 33
    
34.
Bertuglia S, Malandrino S, Colantuoni A. Effect of Vaccinium myrtillus anthocyanosides on ischaemia reperfusion injury in hamster cheek pouch microcirculation. Pharmacol Res 1995;31:183-7.  Back to cited text no. 34
    
35.
Scarabelli TM, Mariotto S, Abdel-Azeim S, Shoji K, Darra E, Stephanou A, et al. Targeting STAT1 by myricetin and delphinidin provides efficient protection of the heart from ischemia/reperfusion-induced injury. FEBS Lett 2009;583:531-41.  Back to cited text no. 35
    
36.
Koh PO. Gingko biloba extract (EGb 761) prevents cerebral ischemia-induced p70S6 kinase and S6 phosphorylation. Am J Chin Med 2010;38:727-34.  Back to cited text no. 36