The Effect of Hydromethanolic Extracts of Mangifera Indica Stem Bark and Leaf on Selected Neurotransmitters in Electroconvulsive Therapy-Induced Seizures in Male Wistar Rats
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Abstract
Electroconvulsive therapy (ECT), although therapeutically efficacious in severe neuropsychiatric disorders, induces profound neurochemical remodeling within limbic circuits. The present study investigated the modulatory effects of Mangifera indica stem bark extract (MSBE) and leaf extract (MLE) on key neurochemical indices in an ECT-induced seizure model. Acetylcholinesterase (AChE), dopamine (DOPA), γ-aminobutyric acid (GABA), and brain-derived neurotrophic factor (BDNF) concentrations were quantified and compared with diazepam (DZP) treatment. ECT alone produced marked elevations in AChE (12.46 ± 0.28 ng/ml), DOPA (12.20 ± 0.86 ng/ml), GABA (6.38 ± 0.20 ng/ml), and BDNF (176.80 ± 6.46 ng/ml) relative to control (6.53 ± 0.09; 5.00 ± 0.55; 1.80 ± 0.21; 114.00 ± 2.28 ng/ml, respectively), indicating enhanced cholinergic turnover, dopaminergic activation, inhibitory neurotransmission, and neurotrophic signaling. DZP co-administration attenuated AChE activity (9.03 ± 0.60 ng/ml) and partially normalized BDNF (125.60 ± 3.31 ng/ml), while sustaining elevated DOPA levels (13.40 ± 0.51 ng/ml). Both MSBE and MLE demonstrated dose-dependent neuromodulatory effects. MSBE (300 and 600 mg/kg) reduced AChE relative to ECT alone (10.53 ± 0.31 and 10.35 ± 0.60 ng/ml, respectively) and moderated GABA concentrations (3.78 ± 0.11 and 3.00 ± 0.04 ng/ml), while maintaining elevated yet controlled BDNF levels (146.00 ± 2.35 and 136.80 ± 2.85 ng/ml). Similarly, MLE (300 and 600 mg/kg) attenuated excessive inhibitory tone (4.42 ± 0.12 and 3.40 ± 0.07 ng/ml GABA) and sustained neurotrophic upregulation (148.40 ± 3.23 and 146.80 ± 3.29 ng/ml BDNF). Notably, both extracts preserved dopaminergic activation without the exaggerated cholinergic and GABAergic elevations observed in the ECT-only group. Collectively, these findings indicate that Mangifera indica stem bark and leaf extracts exert stabilizing effects on excitatory–inhibitory neurotransmitter balance and neurotrophic signaling following ECT-induced seizures. Their ability to recalibrate cholinergic, dopaminergic, and GABAergic indices while sustaining adaptive BDNF upregulation suggests potential neuroprotective and homeostatic properties, supporting further mechanistic and translational investigations.
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References
I. Abiodun, O. O., & Adeneye, A. A. (2020). Neuroprotective effects of Mangifera indica Linn. stem bark extract in rat models of memory impairment. Journal of Complementary and Integrative Medicine, 17(4), 20190307
II. Adewumi, A. et al. (2021). Neuroprotective properties of flavonoids via GABAergic modulation. Neuropharmacology, 185, 108436.
III. Ahmad, W., Shah, A. A., & Khan, M. I. (2023). Neuroprotective role of natural antioxidants in seizure disorders. Frontiers in Pharmacology, 14, 1189237.
IV. Ahmed, A., Ibrahim, M., & Yusuf, M. (2023). Neurobehavioral effects of electroconvulsive therapy in rats: Mechanisms and mitigation strategies. Journal of Neuroscience Research, 101(2), 145-154.
V. Akinmoladun, F. J., Akinrinlola, B. L., & Komolafe, F. L. (2022). Mangifera indica ameliorates cisplatin-induced nephrotoxicity via suppression of oxidative stress and inflammatory mediators. Journal of Ethnopharmacology, 288, 115008.
VI. Akinmoladun, F. J., Lawal, O. A., & Olaleye, T. M. (2022). Antioxidant and neuroprotective activities of Mangifera indica: a review of pharmacological evidence. Journal of Ethnopharmacology, 292, 115229.
VII. Akinmoladun, F. O. et al. (2020). Phytochemical and antioxidant potential of Mangifera indica leaf and stem bark. J Tradit Complement Med, 10(3), 240–247.
VIII. Akinmoladun, F. O., Komolafe, T. O., & Farombi, E. O. (2022). Neuroprotective mechanisms of polyphenolic compounds in neurodegenerative diseases: Targeting oxidative stress and neuroinflammation. Biomedicine & Pharmacotherapy, 153, 113311.
IX. Akinmoladun, F. O., Komolafe, T. R., Ojo, A. S., & Farombi, E. O. (2024). Phytochemical and antioxidant properties of Mangifera indica leaf extracts. Journal of Applied Biomedicine, 22(1), 45–56. https://doi.org/10.1016/j.jab.2024.01.005
X. Akinmoladun, F. O., Oladipo, E. K., & Adekunle, A. S. (2024). Mangifera indica-based phytochemicals: Neuropharmacological and antioxidant properties in experimental models. Journal of Ethnopharmacology, 320, 117206.
XI. Akinmoladun, F. O., Olaleye, T. M., Komolafe, R. O., & Farombi, E. O. (2021). Mangifera indica-derived phytochemicals as potential neuroprotective agents: a review. Phytotherapy Research, 35(2), 598–615.
XII. Aluko, B. T. et al. (2021). Mangiferin-rich plant extracts as acetylcholinesterase inhibitors. Biomed Pharmacother, 138, 111493.
XIII. Arias, B. et al. (2020). Dopaminergic and cholinergic interplay in seizure susceptibility. Epilepsy Res, 159, 106257.
XIV. Bamigboye, M. O., Omotoso, O. T., & Ajibade, A. J. (2024). Modulatory effect of mango leaf extract on neurotransmitter levels in seizure-induced rats. Metabolic Brain Disease, 39(1), 55–63.
XV. Chauhan, A., Sharma, P., & Sandhir, R. (2020). Protective effect of mangiferin in kainic acid-induced seizures and neurotoxicity in rats. Neurochemical Research, 45(4), 823–834. https://doi.org/10.1007/s11064-020-02978-0
XVI. Chen, Q. et al. (2023). Targeting GABAergic dysfunction in seizure disorders. Front Neurol, 14,
XVII. de Oliveira, D. M. et al. (2021). Polyphenols and dopamine modulation: Implications for
neuroprotection. Brain Res Bull, 175, 80–89.
XVIII. Dhir, A., & Naidu, P. S. (2007). Seizure suppression and cognition improvement following combined administration of acetylcholinesterase inhibitor and GABAergic agents in mice. Seizure, 16(4), 340–347. https://doi.org/10.1016/j.
XIX. Diniz, B. S., Teixeira, A. L., & Forlenza, O. V. (2021). Brain-derived neurotrophic factor and cognitive recovery following electroconvulsive therapy: A review of mechanisms. CNS Drugs, 35(3), 281–292.
https://doi.org/10.1007/s40263-021-00797-6
XX. Ghasemi, M., Amini, H., & Haeri, A. (2022). Electroconvulsive therapy-induced cognitive and motor impairments: Mechanisms and potential therapeutic interventions. Neuroscience Letters, 791, 136974.
https://doi.org/10.1016/j.neulet.2022.136974
XXI. Gupta, R., & Dey, P. (2022). Neuroprotective and neuromuscular benefits of mango leaf extract in rotenone-induced Parkinsonism in rats. Biomedicine & Pharmacotherapy, 146, 112597. https://doi.org/10.1016/j.biopha.2021.112597
XXII. Huang, L. et al. (2022). ECT-induced changes in GABAergic activity and neural inhibition. CNS Neurosci Ther, 28(1), 87–95.
XXIII. Joca, S. R. L. et al. (2021). Neurotransmitter interactions and memory impairment in animal models. Pharmacol Ther, 224, 107829.
XXIV. Meyer, J. H., Fontana, R. J., & Seeman, P. (2021). GABA-A receptor modulation in the control of seizure-induced motor dysfunction: Diazepam and beyond. Neuropharmacology, 185, 108431. https://doi.org/10.1016/j.neuropharm.2021.108431
XXV. Ojo, A. et al. (2021). Neurotrophic factors and antioxidant mechanisms of medicinal plants. J Ethnopharmacol, 279, 114341.
XXVI. Ojo, O. A., Anthony, A. A., & Adelakun, A. A. (2023). Neuroprotective and anti-seizure properties of natural antioxidants: Evidence from animal models. Antioxidants, 12(3), 579.
https://doi.org/10.3390/antiox12030579
XXVII. Olaleye, T. M., Bello, O. R., & Oyelowo, O. T. (2021). Cognitive-enhancing effect of Mangifera indica in experimental models of neurotoxicity. Journal of Basic and Clinical Physiology and Pharmacology, 32(4), 387–394. https://doi.org/10.1515/jbcpp-2020-0510
XXVIII. Raza, S. S., Khan, M. M., Ahmad, A., et al. (2021). Neuroinflammatory mechanisms in ECT-induced behavioral impairment: A mechanistic insight. Neurochemistry International, 144, 104999. https://doi.org/10.1016/j.neuint.2021.104999
XXIX. Shah, S. A., Malik, S., & Ullah, R. (2023). Plant-derived neuroprotective agents modulating BDNF and synaptic plasticity. Journal of Ethnopharmacology, 309, 116327.
https://doi.org/10.1016/j.jep.2023.116327
XXX. Sharma, S., Taliyan, R., & Sharma, P. L. (2019). Neuroprotective effects of pioglitazone in electroconvulsive shock-induced cognitive impairment in rats. Brain Research Bulletin, 153,
–10. https://doi.org/10.1016/j.brainresbull.2019.08.006
XXXI. Siedlecka, M., Kossut, M., & Nowicka, D. (2021). Passive avoidance learning and memory: From simple to complex behavioral paradigms. Acta Neurobiologiae Experimentalis, 81(1), 1–14.
XXXII. Silva, L. M., Costa, M. C., & Lima, T. T. (2021). Mangiferin protects against glutamate-induced neurotoxicity: Role of GABAergic transmission. Molecular Neurobiology, 58(1), 225–236. https://doi.org/10.1007/s12035-020-02171-7
XXXIII. Singh, D., Sharma, R., & Verma, S. (2021). Mango leaf extract ameliorates rotenone-induced behavioral deficits in rats via antioxidant and anti-inflammatory actions. Neurochemical Research, 46(3), 584–594. https://doi.org/10.1007/s11064-020-03193-6
XXXIV. Treiman, D. M. (2001). GABAergic mechanisms in epilepsy. Epilepsia, 42(Suppl 3), 8–12.
https://doi.org/10.1046/j.1528-1157.2001.042suppl.3008.x
XXXV. Zhang, Y., Wang, Y., & Liu, T. (2023). Mitochondrial dysfunction in epilepsy and related neuroprotection. Free Radical Biology and Medicine, 200, 208–218.
XXXVI. Zhao, X. et al. (2022). Excessive BDNF expression and its role in seizure models. Brain Res Bull, 183, 93–101.