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image of Cornus mas (Cornelian Cherry) Exerts Neuroprotective Effects on Cerebral Ischemia/Reperfusion Injury via Anti-Inflammatory and Antioxidant Properties

Abstract

Background

Stroke is one of the most important causes of mortality and disability in the world. Over 80% of strokes are ischemic, resulting from blockages in cerebral arteries. Increasing evidence suggests that enriching the diet with nutritional antioxidants could decrease brain damage and enhance cognitive function. Cornelian cherry has anti-inflammatory and antioxidant properties and is introduced as a potential source of active ingredients, like anthocyanins, vitamin C, phenolic compounds, and minerals.

Objective

Our research study aimed to evaluate the neuroprotective impact of (cornelian cherry) on a rat model of Cerebral Ischemia/Reperfusion Injury (CIRI).

Methods

Middle cerebral artery blockage induced CIRI for 60 minutes. After inducing CIRI, intra-peritoneal injections of Extract (CME) were administered for 14 days in a dose-dependent manner (30, 60, and 120 mg/kg body weight). The effects of CME on learning and memory recovery were evaluated using a shuttle box behavioral test.

Two weeks following CIRI, several factors of oxidative stress, such as nitrite (NO2-), Ferric ion Reducing Antioxidant Power (FRAP), and Malondialdehyde (MDA), were measured in the hippocampal tissues and serum. Anti-inflammatory genes, such as miR-125b, and the target genes (TNF-α and iNOS) were evaluated real-time PCR assay. Additionally, neural damage in the CA1 and CA3 regions of the hippocampus was assessed using Hematoxylin and Eosin (H&E) staining.

Results

The avoidance time in the shuttle-box behavior test supported our finding that CME exhibited improved fear memory. Furthermore, it increased the CA1 and CA3 hippocampal post-stroke pyramidal cell layers. Levels of NO2- and MDA were decreased, and FRAP was considerably increased in both the hippocampus and serum by CME. Additionally, CME increased miR-125b expression, while modulating TNF-α and iNOS production in the hippocampal regions.

Conclusion

Based on our findings, we can conclude CME to possess antioxidant and anti-inflammatory properties, which confer neuroprotective potential against CIRI, thereby protecting neurons from ischemic death.

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2024-11-29
2025-01-05
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References

  1. Maddahi A. Kruse L.S. Chen Q.W. Edvinsson L. The role of tumor necrosis factor-α and TNF-α receptors in cerebral arteries following cerebral ischemia in rat. J. Neuroinflammation 2011 8 1 107 10.1186/1742‑2094‑8‑107 21871121
    [Google Scholar]
  2. Kong Z.L. Hsu Y.T. Johnson A. Tsai T.H. Miao S. He J.L. Tsou D. Protective effects of Antrodia camphorata extract against hypoxic cell injury and ischemic stroke brain damage. Phytother. Res. 2021 35 3 1609 1620 10.1002/ptr.6928 33103286
    [Google Scholar]
  3. Asgharzade S. Khorrami M.B. Forouzanfar F. Neuroprotective effect of herniarin following transient focal cerebral ischemia in rats. Metab. Brain Dis. 2021 36 8 2505 2510 10.1007/s11011‑021‑00841‑1 34519909
    [Google Scholar]
  4. Asgharzade S. Talaei A. Farkhondeh T. Forouzanfar F. A review on stem cell therapy for neuropathic pain. Curr. Stem Cell Res. Ther. 2020 15 4 349 361 10.2174/1574888X15666200214112908 32056531
    [Google Scholar]
  5. Lee J.C. Park C.W. Shin M.C. Cho J.H. Lee H.A. Kim Y.M. Park J.H. Ahn J.H. Cho J.H. Tae H.J. Hwang I.K. Lee T.K. Won M.H. Kang I.J. Tumor necrosis factor receptor 2 is required for ischemic preconditioning-mediated neuroprotection in the hippocampus following a subsequent longer transient cerebral ischemia. Neurochem. Int. 2018 118 292 303 10.1016/j.neuint.2018.05.008 29777731
    [Google Scholar]
  6. Ruan Y. Zeng J. Jin Q. Chu M. Ji K. Wang Z. Li L. Endoplasmic reticulum stress serves an important role in cardiac ischemia/reperfusion injury (Review). Exp. Ther. Med. 2020 20 6 1 10.3892/etm.2020.9398 33199993
    [Google Scholar]
  7. Xu Z. Zhao L. Yang X. Ma S. Ge Y. Liu Y. Liu S. Shi J. Zheng D. Mmu-miR-125b overexpression suppresses NO production in activated macrophages by targeting eEF2K and CCNA2. BMC Cancer 2016 16 1 252 10.1186/s12885‑016‑2288‑z 27020049
    [Google Scholar]
  8. Rasheed Z. Rasheed N. Abdulmonem W.A. Khan M.I. MicroRNA-125b-5p regulates IL-1β induced inflammatory genes via targeting TRAF6-mediated MAPKs and NF-κB signaling in human osteoarthritic chondrocytes. Sci. Rep. 2019 9 1 6882 10.1038/s41598‑019‑42601‑3 30626917
    [Google Scholar]
  9. Wang Y. Zeng G. Jiang Y. The emerging roles of miR-125b in cancers. Cancer Manag. Res. 2020 12 1079 1088 10.2147/CMAR.S232388 32104088
    [Google Scholar]
  10. Ma P. Li Y. Zhang W. Fang F. Sun J. Liu M. Li K. Dong L. Long Non-coding RNA MALAT1 Inhibits Neuron Apoptosis and Neuroinflammation While Stimulates Neurite Outgrowth and Its Correlation With MiR-125b Mediates PTGS2, CDK5 and FOXQ1 in Alzheimer’s Disease. Curr. Alzheimer Res. 2019 16 7 596 612 10.2174/1567205016666190725130134 31345147
    [Google Scholar]
  11. Huang H.C. Yu H.R. Huang L.T. Huang H.C. Chen R.F. Lin I.C. Ou C.Y. Hsu T.Y. Yang K.D. miRNA-125b regulates TNF-α production in CD14+ neonatal monocytes via post-transcriptional regulation. J. Leukoc. Biol. 2012 92 1 171 182 10.1189/jlb.1211593 22581933
    [Google Scholar]
  12. Shen Y. Shen Z. Guo L. Zhang Q. Wang Z. Miao L. Wang M. Wu J. Guo W. Zhu Y. MiR-125b-5p is involved in oxygen and glucose deprivation injury in PC-12 cells via CBS/H 2 S pathway. Nitric Oxide 2018 78 11 21 10.1016/j.niox.2018.05.004 29777774
    [Google Scholar]
  13. Dinda B. Kyriakopoulos A.M. Dinda S. Zoumpourlis V. Thomaidis N.S. Velegraki A. Markopoulos C. Dinda M. Cornus mas L. (cornelian cherry), an important European and Asian traditional food and medicine: Ethnomedicine, phytochemistry and pharmacology for its commercial utilization in drug industry. J. Ethnopharmacol. 2016 193 670 690 10.1016/j.jep.2016.09.042 27705748
    [Google Scholar]
  14. Moldovan B. Filip A. Clichici S. Suharoschi R. Bolfa P. David L. Antioxidant activity of Cornelian cherry (Cornus mas L.) fruits extract and the in vivo evaluation of its anti-inflammatory effects. J. Funct. Foods 2016 26 77 87 10.1016/j.jff.2016.07.004
    [Google Scholar]
  15. Sangsefidi Z.S. Hosseinzadeh M. Ranjbar A.M. Akhondi-Meybodi M. Fallahzadeh H. Mozaffari-Khosravi H. The effect of total anthocyanin-base standardized (Cornus mas L.) fruit extract on liver function, tumor necrosis factor α, malondealdehyde, and adiponectin in patients with non-alcoholic fatty liver: a study protocol for a double-blind randomized clinical trial. Nutr. J. 2019 18 1 39 10.1186/s12937‑019‑0465‑z 31324181
    [Google Scholar]
  16. Crisan D. Scharffetter-Kochanek K. Crisan M. Schatz S. Hainzl A. Olenic L. Filip A. Schneider L.A. Sindrilaru A. Topical silver and gold nanoparticles complexed with Cornus mas suppress inflammation in human psoriasis plaques by inhibiting NF ‐κB activity. Exp. Dermatol. 2018 27 10 1166 1169 10.1111/exd.13707 29906306
    [Google Scholar]
  17. Mesgari Abbasi M. Hassanalilou T. Khordadmehr M. Mohammadzadeh Vardin A. Behroozi Kohlan A. Khalili L. Effects of Cornus mas Fruit Hydro-Methanolic Extract on Liver Antioxidants and Histopathologic Changes Induced by Cisplatin in Rats. Indian J. Clin. Biochem. 2020 35 2 218 224 10.1007/s12291‑018‑0809‑z 32226254
    [Google Scholar]
  18. Moradi Z. Rabiei Z. Anjomshoa M. Amini-Farsani Z. Massahzadeh V. Asgharzade S. Neuroprotective effect of wild lowbush blueberry (Vaccinium angustifolium ) on global cerebral ischemia/reperfusion injury in rats: Downregulation of iNOS/TNF‐α and upregulation of miR‐146a/miR‐21 expression. Phytother. Res. 2021 35 11 6428 6440 10.1002/ptr.7296 34580912
    [Google Scholar]
  19. Asgharzadeh S. Therapeutic effects of oleuropein in improving seizure, oxidative stress and cognitive disorder in pentylenetetrazole kindling model of epilepsy in Mice. Iran. J. Pharm. Res. 2020 19 1 98 110 10.22037/ijpr.2019.14212.12209.
    [Google Scholar]
  20. Li P. Stetler R.A. Leak R.K. Shi Y. Li Y. Yu W. Bennett M.V.L. Chen J. Oxidative stress and DNA damage after cerebral ischemia: Potential therapeutic targets to repair the genome and improve stroke recovery. Neuropharmacology 2018 134 Pt B 208 217 10.1016/j.neuropharm.2017.11.011 29128308
    [Google Scholar]
  21. Asgary S. Kelishadi R. Rafieian-Kopaei M. Najafi S. Najafi M. Sahebkar A. Investigation of the lipid-modifying and antiinflammatory effects of Cornus mas L. supplementation on dyslipidemic children and adolescents. Pediatr. Cardiol. 2013 34 7 1729 1735 10.1007/s00246‑013‑0693‑5 23625305
    [Google Scholar]
  22. Demirkaya S. Topcuoglu M.A. Aydin A. Ulas U.H. Isimer A.I. Vural O. Malondialdehyde, glutathione peroxidase and superoxide dismutase in peripheral blood erythrocytes of patients with acute cerebral ischemia. Eur. J. Neurol. 2001 8 1 43 51 10.1046/j.1468‑1331.2001.00166.x 11509080
    [Google Scholar]
  23. Jaghdani H.F. Shomali T. Shahraki G.S. Madiseh R.M. Kopaei R.M. Cornus mas : A review on traditional uses and pharmacological properties. J. Complement. Integr. Med. 2017 14 3 20160137 10.1515/jcim‑2016‑0137 28782352
    [Google Scholar]
  24. Wang Q. Tang X. Yenari M. The inflammatory response in stroke. J. Neuroimmunol. 2007 184 1-2 53 68 10.1016/j.jneuroim.2006.11.014 17188755
    [Google Scholar]
  25. Yamaura K. Ishiwatari M. Yamamoto M. Shimada M. Bi Y. Ueno K. Anthocyanins, but not anthocyanidins, from bilberry (Vaccinium myrtillus L.) alleviate pruritus via inhibition of mast cell degranulation. J. Food Sci. 2012 77 12 H262 H267 10.1111/j.1750‑3841.2012.02974.x 23164040
    [Google Scholar]
  26. Tili E. Michaille J.J. Cimino A. Costinean S. Dumitru C.D. Adair B. Fabbri M. Alder H. Liu C.G. Calin G.A. Croce C.M. Modulation of miR-155 and miR-125b levels following lipopolysaccharide/TNF-α stimulation and their possible roles in regulating the response to endotoxin shock. J. Immunol. 2007 179 8 5082 5089 10.4049/jimmunol.179.8.5082 17911593
    [Google Scholar]
  27. Wang X. Ha T. Zou J. Ren D. Liu L. Zhang X. Kalbfleisch J. Gao X. Williams D. Li C. MicroRNA-125b protects against myocardial ischaemia/reperfusion injury via targeting p53-mediated apoptotic signalling and TRAF6. Cardiovasc. Res. 2014 102 3 385 395 10.1093/cvr/cvu044 24576954
    [Google Scholar]
  28. Zhao L. Ding Y. Zhang L. Li L. Cornel iridoid glycoside improves memory ability and promotes neuronal survival in fimbria–fornix transected rats. Eur. J. Pharmacol. 2010 647 1-3 68 74 10.1016/j.ejphar.2010.08.016 20826142
    [Google Scholar]
  29. Zamani M. Hassanshahi J. Soleimani M. Zamani F. Neuroprotective effect of olive oil in the hippocampus CA1 neurons following ischemia: Reperfusion in mice. J. Neurosci. Rural Pract. 2013 4 2 164 170 10.4103/0976‑3147.112753 23914093
    [Google Scholar]
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  • Article Type:
    Review Article
Keywords: microRNAs ; Cornelian cherry ; oxidative stress ; ischemic stroke
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