31DEC

Welcome To MJPPS

The editors welcome the submission of relevant articles for editorial consideration. Manuscripts should be addressed to the Editor-in-Chief (Prof. Fathi M. Sherif, editor@medjpps.com, f.sherif@uot.edu.ly).
Mediterranean Journal of Pharmacy and Pharmaceutical Sciences
https://ppj.org.ly/article/doi/10.5281/zenodo.23737518

Mediterranean Journal of Pharmacy and Pharmaceutical Sciences

Original article Pharmacology

Post-treatment with Cnidoscolus aconitifolius leaf extract ameliorates neurological and behavioral deficits following cerebral ischemia-reperfusion in rats by modulating oxidative, inflammatory, apoptotic, and neurotransmitter pathways

Stephen B. Asehinde, Gbemisayo A. Abbas, Paul A. Adeleke, Favour B. Jegede, Clinton Ijirigho, Esther T. Ojo, Abayomi M. Ajayi, Olatunde Owoeye, Solomon Umukoro

http://dx.doi.org/10.5281/zenodo.23737518 Mediterr J Pharm Pharm Sci, vol.6, n4, p.40-57, 2026
PDF
PDF
Downloads: 4
Views: 25

Abstract

Oxidative and inflammatory pathways underlie the neuropathology of ischemic stroke, a neurological disease responsible for death and disability in many people worldwide. Studies showed Cnidoscolus aconitifolius exhibited antioxidant, anti-inflammatory, and memory-enhancing activities in rodents. However, its neuro-protective activities in post-stroke events remain poorly understood. This study sought to investigate the neuroprotective activities of an aqueous leaf extract of Cnidoscolus aconitifolius in rats after ischemia/reperfusion. 40 rats were assigned to five experimental groups as follows: Groups 1 (sham control) and 2 (ischemia/reperfusion control) received distilled water (10 mL/kg), respectively. Group 3-5 had Cnidoscolus aconitifolius (50,100, and 200 mg/kg, p.o.) for seven days, following induction of ischemic stroke using bilateral common carotid artery occlusion (BCCAO) procedure. The neurological, motor, and memory skills were evaluated on day seven following reperfusion. Oxidative stress/antioxidant biomarkers, myeloperoxidase, pro-inflammatory cytokines (TNF-α, IL-6), nuclear factor kappa B (NF-κB), glutamic acid decarboxylase, apoptotic biomarker (caspase-3) contents, neuropathological alterations, and serum lipid profile were determined. The results show that Cnidoscolus aconitifolius post-treatment significantly attenuated neurological, motor, and memory deficits in rats after reperfusion in the BCCAO model. Furthermore, Cnidoscolus aconitifolius post-treatment significantly reduced brain oxidative stress biomarkers, myeloperoxidase, pro-inflammatory cytokines, NF-κB, and caspase-3, while normalizing serum lipid profiles in rats with ischemic stroke. Administration of Cnidoscolus aconitifolius reduces the extent of brain damage, significantly enhances neuronal viability, increases neuronal antioxidant defenses, and increases glutamic acid decarboxylase activity in ischemic rats after reperfusion. The findings demonstrated that post-treatment with Cnidoscolus aconitifolius enhances functional recovery in ischemic rats after reperfusion. This recovery is driven by the activation of neuroprotective pathways, as evidenced by reduced brain damage, increased glutamic acid decarboxylase activity, and enhanced antioxidant defenses.

Keywords

Bilateral common carotid artery occlusion, ischemic stroke, neurological deficit, neuroprotection, rat

References

  1. Jurcau A, Simion A. Neuroinflammation in cerebral ischemia and ischemia/reperfusion injuries: From pathophysiology to therapeutic strategies. International Journal of Molecular Sciences. 2021; 23: 14. doi: 10.3390/ ijms23010014
  2. Majumder D. Ischemic stroke: Pathophysiology and evolving treatment approaches. Neuroscience Insights. 2024; 9: 26331055241292600. doi: 10.1177/26331055241292600
  3. Feigin VL, Brainin M, Norrving B, Martins SO, Pandian J, Lindsay PF, et al. World Stroke Organization: Global Stroke Fact Sheet. International Journal of Stroke. 2025; 20: 132-144. doi: 10.1177/17474930241308142
  4. Hart RG, Catanese L, Perera KS, Ntaios G, Connolly SJ. Embolic stroke of undetermined source: A systematic review and clinical update. Stroke. 2014; 48: 867-872. doi: 10.1161/STROKEAHA.116.016414
  5. Raman G, Moorthy D, Hadar N, Dahabreh I, O'Donnell T, Thaler D, et al. Management strategies for asymptomatic carotid stenosis: A systematic review and meta-analysis. Annals Internal Medicine. 2013; 158: 676-685. doi: 10.7326/0003-4819-158-9-201305070-00007
  6. Umukoro S, Oghwere EE, Ben-Azu B, Owoeye O, Ajayi AM, Omorogbe O, Okubena O. Jobelyn® ameliorates neurological deficits in rats with ischemic stroke through inhibition of the release of pro-inflammatory cytokines and NF-κB signaling pathway. Pathophysiology. 2019; 26: 77-88. doi: 10.1016/j.pathophys.2018.10.002
  7. Salaudeen M, Bello N, Danraka R, Ammani M. Understanding the pathophysiology of ischemic stroke: The basis of current therapies and opportunity for new Ones. Biomolecules. 2024; 14: 305. doi: 10.3390/biom 14030305
  8. Kim J, Fann D, Seet RC, Jo D, Mattson M, Arumugam T. Phytochemicals in ischemic stroke. Neuromolecular Medicine. 2016; 18: 283-305. doi: 10.1007/s12017-016-8403-0
  9. Anrather J, Iadecola C. Inflammation and stroke: An overview. Neurotherapeutics. 2016; 13: 661-670. doi: 10.1007/ s13311-016-0483-x
  10. Ezejimofor M, Uthman O, Maduka O, Ezeabasili A, Onwuchekwa A, Ezejimofor B. Stroke survivors in Nigeria: A door-to-door prevalence survey from the Niger Delta region. Journal of the Neurological Sciences. 2017; 372: 262-269. doi: 10.1016/j.jns.2016.11.059
  11. Hu D, Huang J, Wang Y, Zhang D, Qu Y. Fruits and vegetables consumption and risk of stroke: A meta-analysis of prospective cohort studies. Stroke. 204; 45(6): 1613-1619. doi: 10.1161/STROKEAHA.114.004836
  12. Adeleke PA, Annafi OS, Ajayi AM, Ben-Azu B, Okubena O, Umukoro S. Sorghum bicolor-based supplement reduces oxidative stress and pro-inflammatory cytokines to mitigate rotenone-induced Parkinsonian-like motor dysfunctions in rats. Mediterranean Journal of Pharmacy and Pharmaceutica Sciences. 2024; 4(3): 15-26. doi: 10.5281/zenodo.13309953
  13. Nizamuddin SFS. Polyphenol-rich black chokeberry (Aronia melanocarpa) and its therapeutic potential in type 2 diabetes mellitus: A comprehensive review. Mediterranean Journal of Medicine and Medical Sciences. 2025; 1(3): 31-42. doi: 10.5281/zenodo.17619107
  14. Pacifici F, Rovella V, Pastore D, Bellia A, Abete P, Donadel G, et al. Polyphenols and ischemic stroke: Insight into one of the best strategies for prevention and treatment. Nutrients. 2021; 13(6):1967. doi: 10.3390/nu13061967
  15. Panghal A, Shaji AO, Nain K, Garg MK, Chhikara N. Cnidoscolus aconitifolius: Nutritional, phytochemical composition and health benefits: A review. Bioactive Compounds in Health and Disease. 2021; 4: 260-286. doi: 10.31989/bchd.v4i11.865
  16. Ramírez Rodrigues MM, Metri Ojeda JC, González Díaz M, Baigts Allende DK. Use of chaya (Cnidoscolous chayamansa) leaves for nutritional compounds production for human consumption. Journal of the Mexican Chemical Society. 2021; 65: 118-128. doi: 10.29356/jmcs.v65i1.1433
  17. Ramos‐Gome M, Figueroa‐Pérez MG, Guzmán‐Maldonado H, Loarca‐Piña G, Mendoza S, Quezada‐Tristán T, et al. Phytochemical profile, antioxidant properties and hypoglycemic effect of chaya (Cnidoscolus chayamansa) in Stz‐induced diabetic rats. Journal of Food Biochemistry. 2017; 41: e12281. doi: 10.1111/jfbc.12281
  18. Adebayo OG, Onasanwo SA, Ajayi AM, Aduema W, Oyebanjo OT, Nicodemu OU. Cnidoscolus aconitifolius-supplemented diet enhanced neurocognition, endogenous antioxidants and cholinergic system and maintains hippocampal neuronal integrity in male Wistar rats. Drug Metabolism Personal Therapeutics. 2022; 37: 81-93. doi: 10.1515/dmpt-2021-0138
  19. Quintal Martínez JP, Segura Campos MR. Cnidoscolus aconitifolius (Mill.) I.M. Johnst.: A food proposal against thromboembolic diseases. Food Reviews International. 2023; 39(3): 1377-1410. doi: 10.1080/87559129.2021. 1934002
  20. Adaramoye AO, Aluko A, Oyagbemi AA. Cnidoscolus aconitifolius Leaf extract protects against hepatic damage induced by chronic ethanol administration in Wistar rats. Alcohol and Alcoholism. 2011; 46: 451- 458. doi: 10.1093/alcalc/agr060
  21. De Ryck M, Van Reempts J, Borgers M, Wauquier A, Janssen PA. Photochemical stroke model: Flunarizine prevents sensorimotor deficits after neocortical infarcts in rats. Stroke. 1999; 20(10): 1383-1390. doi: 10.1161/ 01.STR.20.10.1383
  22. Ajayi AM, Ben-Azu B, Godson JC, Umukoro S. Effect of Spondias mombin fruit extract on scopolamine-induced memory impairment and oxidative stress in mouse brain.  Journal of Herbs, Spices and Medicinal Plants. 2021; 27: 24-36. doi: 10.1080/10496475.2020.1777613
  23. Ghassemi S, Gholami Pourbadie H, Prehaud C, Lafon M, Sayyah M. Role of the glycoprotein thorns in the anxious effects of rabies virus: Evidence from an animal study. Brain Research Bulletin. 2022; 185: 107-116. doi: 10.1016/j. brainresbull.2022.05.001
  24. Abbas AG, Ajiboye OB, Adeleke PA, Ajayi AM, Okubena O, Umukoro S. Polyphenol-rich Sorghum bicolor supplement exhibits anti-nociceptive activity and protective effects against pathological changes associated with complete Freund's adjuvant-induced arthritis in rodents. Pharmacological Research-Modern Chinese Medicine. 2024; 12: 100481. doi: 10.1016/j.prmcm.2024.100481
  25. Bazine HA, Shlaka MA, Mezogi JS, Alghazeer RO, Sherif FM. Phytochemical and pharmacological studies of Lycium schweinfurthii methanolic leaves extract (Solanaceae) in mice. Pharmacy and Pharmacology International Journal. 2022; 10(6): 201-206. doi: 10.15406/ppij.2022.10.00386.
  26. Bazine HA, Shalka MA, Sherif FM. A neuropharmacological profile of Lycium schweinfurthii (Solanaceae) methanolic extract in mice. Mediterranean Journal of Pharmacy and Pharmaceutica Sciences. 2023; 3(1): 42 - 49. doi: 10.5281/zenodo.7771364
  27. Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Analytical Biochemistry. 1979; 95: 351-358. doi: 10.1016/0003-2697(79)90738-3
  28. Adeleke PA, Annafi OS, Ajayi AM, Ben-Azu B, Okubena O, Umukoro S. Sorghum bicolor-based supplement reduces oxidative stress and pro-inflammatory cytokines to mitigate rotenone-induced Parkinsonian-like motor dysfunctions in rats. Mediterranean Journal of Pharmacy and Pharmaceutical Sciences. 2024; 4(3): 15-26. doi: 10.5281/zenodo.13309953
  29. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. Journal of Biological Chemistry. 1951; 193: 265-275. doi: 10.1016/S0021-9258(19)52451-6
  30. Yu K, Hu S, Huang J, Mei LH. A high-throughput colorimetric assay to measure the activity of glutamate decarboxylase. Enzyme Microbiology Technology. 2011; 49: 272-276. doi: 10.1016/j.enzmictec.2011.06.007
  31. Suzuki K, Ota H, Sasagawa S, Sakatani T, Fujikura T. Assay method for myeloperoxidase in human polymorphonuclear leukocytes. Analytic Biochemistry. 1983; 132: 345-352. doi: 10.1016/0003-2697(83)90019-2
  32. Taveira KM, Kleber TC, Carlos HC, da Silva LL. Morphological and morphometric analysis of the hippocampus in Wistar rats with experimental hydrocephalus. Pediatric Neurosurgery. 2013; 48: 163-167. doi: 10.1159/ 000345959
  33. Girard S, Murray KN, Rothwell NJ, Metz GA, Allan SM. Long-term functional recovery and compensation after cerebral ischemia in rats. Behavioural Brain Research. 2014; 15: 270: 18-28. doi: 10.1016/j.bbr.2014.05.008
  34. Ji S, Kronenberg G, Balkaya M, Färber K, Gertz K, Kettenmann H. Acute neuroprotection by pioglitazone after mild brain ischemia without effect on long-term outcome. Experimental Neurology. 2009; 216: 321-328. doi: 10.1016/j.expneurol.2008.12.007
  35. Farkas E, Luiten PG, Bari F. Permanent, bilateral common carotid artery occlusion in the rat: A model for chronic cerebral hypoperfusion-related neurodegenerative diseases. Brain Research Review. 2007; 54: 162-180. doi: 10.1016/j.brainresrev.2007.01.003
  36. Kim YW. Update on stroke rehabilitation in motor impairment. Brain Neurorehabilitation. 2022; 15: e12. doi: 10.12786/bn.2022.15.e12
  37. Feigin VL, Barker-Collo S, McNaughton H, Brown P, Kerse N. Long-term neuropsychological and functional outcomes in stroke survivors: Current evidence and perspectives for new research. International Journal of Stroke. 2008; 3: 33-40. doi: 10.1111/j.1747-4949.2008.00177.x
  38. Wright F, Wu S, Chun HYY, Mead G. Factors associated with poststroke anxiety: A systematic review and meta‐analysis. Stroke Research Treatment. 2017; 2124743. doi: 10.1155/2017/2124743
  39. Knapp P, Dunn-Roberts A, Sahib N, Cook L, Astin F, Kontou E, Thomas SA. Frequency of anxiety after stroke: An updated systematic review and meta-analysis of observational studies. International Journal of Stroke. 2020; 15: 244-255. doi: 10.12786/bn.2022.15.e12
  40. Babalola KT, Oyebanjo O, Adekoya VA, Adeniyi IA, Ajayi AM, Onasanwo SA. Protective effect of methanol leaf extract of Cnidoscolus aconitifolius against lipopolysaccharide-induced cortico-hippocampal neuroinflammation, oxidative stress and memory impairment. Advances in Traditional Medicine. 2023; 23: 145-155. doi: 10.1007/s 13596-021-00578-3
  41. Tuwar MN, Chen WH, Yeh HL, Bai CH. Association between brain-derived neurotrophic factor and lipid profiles in acute ischemic stroke patients. International Journal of Molecular Sciences. 2024; 25: 2380. doi: 10.3390/ijms 25042380
  42. Chukwu E, Osuocha KU, Iwueke AV. Phytochemical profiling, body weight effect, and anti-hypercholesterolemia potentials of Cnidoscolus aconitifolius leaf extracts in male albino rat. Journal of Pharmacognosy and Phytotherapy. 2020; 12: 19-27. doi: 10.5897/JPP2016.0436
  43. Bleilevens C, Roehl AB, Goetzenich A, Zoremba N, Kipp M, Dang J, et al. Effect of anesthesia and cerebral blood flow on neuronal injury in a rat middle cerebral artery occlusion (MCAO) model. Experimental Brain Research. 2023; 224(2): 155-164. doi: 10.1007/s00221-012-3296-0
  44. Canazza A, Minati L, Boffano C, Parati E, Binks S. Experimental models of brain ischemia: a review of techniques, magnetic resonance imaging, and investigational cell-based therapies. Frontiers in Neurology. 2014; 5: 19. doi: 10.3389/fneur.2014.00019
  45. De Meyer SF, Denorme F, Langhauser F, Geuss E, Fluri F, Kleinschnitz C. Thrombo-inflammation in stroke brain damage. Stroke. 2016; 47: 1165-1172. doi: 10.1161/STROKEAHA.115.011238
  46. Pawluk H, Tafelska-Kaczmarek A, Sopońska M, Porzych M, Modrzejewska M, Pawluk M, et al. The influence of oxidative stress markers in patients with ischemic stroke. Biomolecules. 2024; 14: 1130. doi: 10.3390/biom 14091130
  47. Morgan MJ, Liu ZG. Crosstalk of reactive oxygen species and NF-κB signaling. Cell Research. 2021; 21: 103-115.  doi: 10.1038/cr.2010.178
  48. Zhang M, Liu Q, Meng H, Duan H, Liu X, Wu J, et al. Mechanisms and therapeutic strategies of ischemia-reperfusion injury. Cell Communication Signaling. 2024; 22: 130. doi: 10.1021/acsptsci.4c00272
  49. Maiocchi SL, Ku J, Thai T, Chan E, Rees MD, Thomas SR. Myeloperoxidase: A versatile mediator of endothelial dysfunction and therapeutic target during cardiovascular disease. Pharmacology and Therapeutics. 2021; 221: 107711. doi: 10.1016/j.pharmthera.2020.107711
  50. Liu W, Wang YR, Wu H, Cui W, Xu X. The role of myeloperoxidase in the pathogenesis of stroke. Brain Research. 2025; 149705. doi: 10.1016/j.brainres.2025.149705
  51. Clarkson AN. Perisynaptic GABA receptors: The overzealous protector. Advanced Pharmacological Science. 2012; 708428. doi: 10.1155/2012/708428
  52. Dade M, Berzero G, Izquierdo C, Giry M, Benazra M, Delattre JY, et al. Neurological syndromes associated with anti-GAD antibodies. International Journal of Molecular Sciences. 2020; 21: 3701. doi: 10.3390/ijms21103701
  53. AL-Hamdani AH. Imbalance of oxidative stress and its role in Parkinson's disease. Mediterranean Journal of Medicine and Medical Sciences. 2026; 2(3): 106-114. doi: 10.5281/zenodo.22403543
  54. Omogunwa TS, Karigidi KO, Akintimehin ES, Didunyemi O.M, Ogunbameru FE, Adetuyi FO. Molecular insights into the oxidative stress-inflammation nexus: Review on the mechanisms and consequences for human health. Mediterranean Journal of Medical Research. 2026; 3(3): 265-277. doi: 10.5281/zenodo.22095911
  55. Sullivan PG, Keller JN, Bussen WL, Scheff SW. Cytochrome c release and caspase activation after traumatic brain injury. Brain Research. 2002; 949(1-2): 88-96. doi: 10.1016/s0006-8993(02)02968-2
  56. Sarkaki AH, Fathimoghaddam S, Mansouri MS, Korrani G, Saki YF. Gallic acid improves cognitive, hippocampal long-term potentiation deficits and brain damage induced by chronic cerebral hypoperfusion in rats. Pakistan Journal of Biological Sciences. 2014; 17: 978-990. doi: 10.3923/pjbs.2014.978.990

Submitted date:
08/19/2026

Reviewed date:
10/15/2026

Accepted date:
10/22/2026

Publication date:
10/28/2026

6ae18caaa953952ff7606695 medjpps Articles
Links & Downloads
2789-1895 (Electronic) 2958-3101 (Printed)
Mediterr J Pharm Pharm Sci ©2026 All rights reserved for this website content. Articles follow their own licenses.

Mediterr J Pharm Pharm Sci

Share this page
Page Sections