Protective Effects of Jujube Extract against Permeability of Blood-Brain Barrier, and the Activity of Glutathione Peroxidase and Catalase in Stroke Model

Document Type : Original Article (s)

Authors

1 Assistant Professor, Department of Biology, School of Basic Sciences, Farhangian University, Tehran, Iran

2 Assistant Professor, Department of Biology, School of Basic Sciences, Malayer University, Malayer, Iran

Abstract

Background: Jujube is a medicinal plant, with strong antioxidant properties that is consumed in worldwide as food and medicine. Recent studies indicate that jujube extracts can suppress inflammation and reduce oxidative stress. Considering that brain ischemia is the third most common cause of death in developed countries, the aim of this study was to investigate the effects of juvenile neuronal protection against stroke-induced damage on the blood-brain barrier, and the activity of two anti-oxidants, glutathione peroxidase and catalase.Methods: In this experimental study, 15 groups of 7 Wistar male rats were used as follows: 2 control groups of saline, 2 sham groups, 2 groups of stroke, and control and stroke groups at doses of 100, 250, and 500 mg/kg/day of jujube extract. After 30 days of oral administration, the animals were subjected to middle cerebral artery occlusion (MCAO) for 60 minutes. After 24 hours of reperfusion, the activity levels of glutathione peroxidase (GPX) and catalase were investigated in the areas of cortex and hippocampus; the permeability of the blood-brain barrier (BBB) was investigated as well.Findings: Oral administration of jujube extract at the dose of 250 mg/kg/day reduced the permeability of the blood-brain barrier in stroke model. Doses of 500 and 250 mg/kg/day of jujube in the cortex and hippocampus, and the dose of 100 mg/kg/day in the hippocampus increased catalase activity.Conclusion: The results of this study clearly show that jujube has a significant potential for stroke prevention.

Keywords


  1. Ganesh A, Luengo-Fernandez R, Wharton RM, Gutnikov SA, Silver LE, Mehta Z, et al. Time course of evolution of disability and cause-specific mortality after ischemic stroke: Implications for trial design. J Am Heart Assoc 2017; 6(6): e005788.
  2. Kodavanti PR, Royland JE, Moore-Smith DA, Besas J, Richards JE, Beasley TE, et al. Acute and subchronic toxicity of inhaled toluene in male Long-Evans rats: Oxidative stress markers in brain. Neurotoxicology 2015; 51: 10-9.
  3. Wang XH, You YP. Epigallocatechin gallate extends therapeutic window of recombinant tissue plasminogen activator treatment for brain ischemic stroke: A randomized double-blind and placebo-controlled Trial. Clin Neuropharmacol 2017; 40(1): 24-8.
  4. Chan PH. Reactive oxygen radicals in signaling and damage in the ischemic brain. J Cereb Blood Flow Metab 2001; 21(1): 2-14.
  5. Li L, Wang N, Jin Q, Wu Q, Liu Y, Wang Y. Protection of Tong-Qiao-Huo-Xue decoction against Cerebral Ischemic Injury through Reduction Blood-Brain Barrier Permeability. Chem Pharm Bull (Tokyo) 2017; 65(11): 1004-10.
  6. Aldini G, Yeum KJ, Niki E, Russell RM. Biomarkers for Antioxidant Defense and Oxidative Damage: Principles and Practical Applications. Hoboken, NJ: Wiley; 2011.
  7. Kiani A, Khorvash F, Hasanzadeh A, Askari G. Relationship between dietary intake and body composition with carotid intima-media thickness in patients with transient ischemic attack. J Isfahan Med Sch 2017; 34(414): 1617-26. [In Persian].
  8. Ji X, Peng Q, Yuan Y, Shen J, Xie X, Wang M. Isolation, structures and bioactivities of the polysaccharides from jujube fruit (Ziziphus jujuba Mill.): A review. Food Chem 2017; 227: 349-57.
  9. Li JW, Fan LP, Ding SD, Ding XL. Nutritional composition of five cultivars of chinese jujube. Food Chemistry 2007; 103(2): 454-60.
  10. Lam CT, Gong AG, Lam KY, Zhang LM, Chen JP, Dong TT, et al. Jujube-containing herbal decoctions induce neuronal differentiation and the expression of anti-oxidant enzymes in cultured PC12 cells. J Ethnopharmacol 2016; 188: 275-83.
  11. Gupta S, Gupta YK. Combination of Zizyphus jujuba and silymarin showed better neuroprotective effect as compared to single agent in MCAo-induced focal cerebral ischemia in rats. J Ethnopharmacol 2017; 197: 118-27.
  12. Taati M, Alirezaei M, Meshkatalsadat M H, Rasoulian B, Dezfolian O, Neamati S. Antioxidant effects of aqueous fruit extract of Ziziphus jujuba on ethanol-induced oxidative stress in the liver and kidney of male rats. Yafte 2011; 13(2): 54-68. [In Persian].
  13. Varnaseri M, Rahnema M, Bigdeli M. The effect of pre-feeding with Purslane seed oil (Portulaca oleracea) on brain stroke volume (MCAO model) in the rat animal model. J Isfahan Med Sch 2015; 33(344): 1197-1210. [In Persian].
  14. Alavian F, Hajizadeh S, Bigdeli MR, Javan M. The role of protein kinase C in ischemic tolerance induced by hyperoxia in rats with stroke. EXCLI J 2012; 11: 188-97.
  15. Miri M M, Mohammadi P. Evaluation of oxidative stress biomarkers in patients with medullary thyroid carcinoma and compared to healthy subjects. J Mil Med. 2017; 19 (1): 84-90. [In Persian].
  16. Knowland D, Arac A, Sekiguchi KJ, Hsu M, Lutz SE, Perrino J, et al. Stepwise recruitment of transcellular and paracellular pathways underlies blood-brain barrier breakdown in stroke. Neuron 2014; 82(3): 603-17.
  17. Lerouet D, Beray-Berthat V, Palmier B, Plotkine M, Margaill I. Changes in oxidative stress, iNOS activity and neutrophil infiltration in severe transient focal cerebral ischemia in rats. Brain Res 2002; 958(1): 166-75.
  18. Lipton P. Ischemic cell death in brain neurons. Physiol Rev 1999; 79(4): 1431-568.
  19. Asgary S, Rafieian-kopaei M, Goli-malekabadi N. The Effects of Jujube Fruit (Ziziphus vulgaris) Powder in Antioxidant Capacity Elevation and Prevent of Inflammation Detection Due to Diabetes in Wistar Rat. J Ilam Univ Med Sci 2016; 24(5): 55-64. [In Persian].
  20. Fu Y, Cheng WH, Porres JM, Ross DA, Lei XG. Knockout of cellular glutathione peroxidase gene renders mice susceptible to diquat-induced oxidative stress. Free Radic Biol Med 1999; 27(5-6): 605-11.
  21. Gu W, Zhao H, Yenari MA, Sapolsky RM, Steinberg GK. Catalase over-expression protects striatal neurons from transient focal cerebral ischemia. Neuroreport 2004; 15(3): 413-6.
  22. Brekke E, Berger HR, Wideroe M, Sonnewald U, Morken TS. Glucose and Intermediary Metabolism and Astrocyte-Neuron Interactions Following Neonatal Hypoxia-Ischemia in Rat. Neurochem Res 2017; 42(1): 115-32.