Landolphia owariensis Reduces Alcohol-Induced Neuroinflammation, Oxidative Stress, and Modulates GFAP and NF Expressions in the Prefrontal Cortex of Rats Exposed to Binge Alcohol
DOI:
https://doi.org/10.47081/njn2025.16.2/001Keywords:
Alcohol use disorder, Neuroinflammation, Medicinal plant, Nutraceuticals, Landolphia owariensisAbstract
Alcohol use disorder (AUD), a neurodegenerative-driven mental health condition, lacks satisfactory treatment, prompting the exploration of polypharmacological approaches. Medicinal plants offer a natural solution for polypharmacology, as they contain multiple pharmacologically active compounds, thus eliminating the complexities and risks of combining multiple synthetic pharmaceutical agents. This study investigated the neuroprotective potential of Landolphia owariensis (LO), a medicinal plant, on alcohol-induced neurodegeneration. Thirty-two male rats were randomly allocated into three groups (n = 10 per group) and subjected to a four-day binge alcohol regimen. The control rats received daily oral doses of 5 g/kg of a nutritional shake diet (NSD), Vitamilk®. A set of rats was given 5 g/kg of 25% ethanol diluted NSD 50% v/v. The last cohort of rats received an oral dosage of 100 mg of LO and 5 g/kg of 25% ethanol in diluted (50% v/v) NSD. Rats were sacrificed at the end of the 4th day; brain samples were isolated and subjected to histological, immunohistochemical, and biochemical analysis. Results revealed that alcohol intake increased lipid peroxidation and neurodegeneration in the prefrontal cortex (PFC), with elevated glial fibrillary acidic protein (GFAP) and neurofilament (NF) expression. In contrast, LO administration reduced lipid peroxidation and neurodegeneration, downregulating GFAP and NF protein expression. These findings demonstrate the neuroprotective effects of LO and suggest its potential development as a supplementary agent for AUD management. The mechanism underlying this neuroprotection may partly involve the downregulation of GFAP and NF protein expression, highlighting that LO has the potential to modulate neuroinflammatory responses.
Downloads
References
Abbott Nutrition (2024). Ensure Original Shake. Available at: https://www.abbottnutrition.com/our-products/ensure -original-shake (Accessed March 30, 2025).
Adewunmi, C., and Sofowora, E. (1980). Preliminary screening of some plant extracts for molluscicidal activity. Planta Med 39, 57–65. doi: 10.1055/s-2008-1074903
Ajayi, A. M., Melete, J., Ben‐Azu, B., and Umukoro, S. (2023). Aggressive‐like behaviour and neurocognitive im-pairment in alcohol herbal mixture‐fed mice are associated with increased neuroinflammation and neuronal apoptosis in the prefrontal cortex. J Biochem Molecular Toxicol 37, e23252. doi: 10.1002/jbt.23252
Andersen, J. V., Schousboe, A., and Wellendorph, P. (2023). Astrocytes regulate inhibitory neurotransmission through GABA uptake, metabolism, and recycling. Essays Biochem 67, 77–91. doi: 10.1042/EBC20220208
Araujo, I., Henriksen, A., Gamsby, J., and Gulick, D. (2021). Impact of alcohol abuse on susceptibility to rare neurodegenerative diseases. Front Mol Biosci 8, 643273. doi: 10.3389/fmolb.2021.643273
Atawodi, S. E., and Alafiatayo, A. A. (2007). Assessment of the phytochemical and antitrypanosomal properties of some extracts of leaves, stem and root bark of Landolphia sp., P. Beauv. Journal of Ethnopharmacology 114, 207–211. doi: 10.1016/j.jep.2007.08.001
Ay, A., Çam, C., Kilinç, A., Fatih Önsüz, M., and Meti̇Ntaş, S. (2025). Prevalence of hazardous alcohol consumption and evaluation of associated factors in university students. Soc Psychiatry Psychiatr Epidemiol 60, 223–233. doi: 10.1007/s00127-024-02680-8
Baumgärtel, C., and Lautenschläger, T. (2023). The genus Landolphia P.Beauv. (Apocynaceae): A comprehensive review on its ethnobotanical utilizations, pharmacology and nutritional potential. J Ethnopharmacol 303, 115946. doi: 10.1016/j.jep.2022.115946
Bennett, M. L., and Viaene, A. N. (2021). What are activat-ed and reactive glia and what is their role in neurodegen-eration? Neurobiol Dis 148, 105172. doi: 10.1016/j.nbd.2020.105172
Cardiff, R. D., Miller, C. H., and Munn, R. J. (2014). Manual hematoxylin and eosin staining of mouse tissue sections. Cold Spring Harb Protoc 2014, pdb.prot073411. doi: 10.1101/pdb.prot073411
Charles, O. A., Patrick, I. S., and Godwin, A. O. (2016). Jobelyn® supplement lowered neuronal degeneration: sig-nificance of altered p53 and ɤ-enolase protein expressions in prefrontal cortex of rat exposed to ethanol. Ann Neurosci 23, 139–148. doi: 10.1159/000449179
Chauhan, R. S., Malik, Y. S., Saminathan, M. and Tripathi, B. N. (2024). Techniques in immunopathology. In Essentials of Veterinary Immunology and Immunopathology. (Singapore: Springer Nature), 577-621.
Cizkova, K., Foltynkova, T., Gachechiladze, M., and Tauber, Z. (2021). comparative analysis of immunohistochemical staining intensity determined by light microscopy, ImageJ and QuPath in placental Hofbauer cells. Acta Histochem Cytochem 54, 21–29. doi: 10.1267/ahc.20-00032
Crews, F. T., and Nixon, K. (2009). Mechanisms of neuro-degeneration and regeneration in alcoholism. Alcohol and Alcoholism 44, 115–127. doi: 10.1093/alcalc/agn079
De Luca, C., Virtuoso, A., Korai, S. A., Cirillo, R., Gargano, F., Papa, M., et al. (2022). Altered spinal homeostasis and maladaptive plasticity in GFAP null mice following peripheral nerve injury. Cells 11, 1224. doi: 10.3390/cells11071224
Ding, Z.-B., Song, L.-J., Wang, Q., Kumar, G., Yan, Y.-Q., and Ma, C.-G. (2021). Astrocytes: a double-edged sword in neurodegenerative diseases. Neural Regen Res 16, 1702. doi: 10.4103/1673-5374.306064
Escartin, C., Guillemaud, O., and Carrillo‐de Sauvage, M. (2019). Questions and (some) answers on reactive astro-cytes. Glia 67, 2221–2247. doi: 10.1002/glia.23687
Ezike, A. C., Okonkwo, C. H., Akah, P. A., Okoye, T. C., Nworu, C. S., Mbaoji, F. N., et al. (2016). Landolphia owar-iensis leaf extracts reduce parasitemia in Plasmodium berghei- infected mice. Pharm Biol 54, 2017–2025. doi: 10.3109/13880209.2016.1138970
Fan, Y. -Y., and Huo, J. (2021). A1/A2 astrocytes in central nervous system injuries and diseases: Angels or devils? Neurochem Int 148, 105080. doi: 10.1016/j.neuint.2021. 105080
Fowler, A. -K., Thompson, J., Chen, L., Dagda, M., Dertien, J., Dossou, K. S. S., et al. (2014). Differential sensitivity of prefrontal cortex and hippocampus to alcohol-induced toxicity. PLoS ONE 9, e106945. doi: 10.1371/journal.pone.0106945
Furukawa, A., Kawamoto, Y., Chiba, Y., Takei, S., Haseg-awa-Ishii, S., Kawamura, N., et al. (2011). Proteomic iden-tification of hippocampal proteins vulnerable to oxidative stress in excitotoxin-induced acute neuronal injury. Neuro-biol Dis 43, 706–714. doi: 10.1016/j.nbd.2011.05.024
Gradisnik, L., and Velnar, T. (2023). Astrocytes in the cen-tral nervous system and their functions in health and dis-ease: A review. World J Clin Cases 11, 3385–3394. doi: 10.12998/wjcc.v11.i15.3385
Guerin, S. P., Melbourne, J. K., Dang, H. Q., Shaji, C. A., and Nixon, K. (2023). Astrocyte reactivity and neuro-degeneration in the female rat brain following alcohol de-pendence. Neuroscience 529, 183–199. doi: 10.1016/j.neuroscience.2023.08.016
Gutteridge, J. M. C., and Wilkins, S. (1982). Copper‐dependent hydroxyl radical damage to ascorbic acid: For-mation of a thiobarbituric acid‐reactive product. FEBS Let-ters 137, 327–330. doi: 10.1016/0014-5793(82)80377-3
Hsu, S., Raine, L., and Fanger, H. (1981). The use of antiavidin antibody and avidin-biotin-peroxidase complex in immunoperoxidase technics. Am J Clin Pathol 75, 816–821. doi: 10.1093/ajcp/75.6.816
Ismael, D. L., Yaya, F., Claude, K. A. L., and José, L. A. (2020). Evaluation of the acute toxicity of liana bark of lan-dolphia owariensis p. beauv. (apocynaceae). Int J Res Granthaalayah 8, 167–172. doi: 10.29121/granthaalayah. v8.i4.2020.22
Jena, A. B., Samal, R. R., Bhol, N. K., and Duttaroy, A. K. (2023). Cellular Red-Ox system in health and disease: The latest update. Biomed Pharmacother 162, 114606. doi: 10.1016/j.biopha.2023.114606
Knapp, D. J., and Crews, F. T. (1999). Induction of cy-clooxygenase‐2 in brain during acute and chronic ethanol treatment and ethanol withdrawal. Alcoholism Clin & Exp Res 23, 633–643. doi: 10.1111/j.1530-0277.1999.tb04165.x
Lemon, R. N., Baker, S. N., and Kraskov, A. (2021). Clas-sification of cortical neurons by spike shape and the identi-fication of pyramidal neurons. Cerebral Cortex 31, 5131–5138. doi: 10.1093/cercor/bhab147
Lohoff, F. W. (2022). Targeting unmet clinical needs in the treatment of alcohol use disorder. Front Psychiatry 13, 767506. doi: 10.3389/fpsyt.2022.767506
MacKillop, J., Agabio, R., Feldstein Ewing, S. W., Heilig, M., Kelly, J. F., Leggio, L., et al. (2022). Hazardous drinking and alcohol use disorders. Nat Rev Dis Primers 8, 80. doi: 10.1038/s41572-022-00406-1
Marshall, S. A., McClain, J. A., Kelso, M. L., Hopkins, D. M., Pauly, J. R., and Nixon, K. (2013). Microglial activation is not equivalent to neuroinflammation in alcohol-induced neurodegeneration: The importance of microglia phenotype. Neurobiol Dis 54, 239–251. doi: 10.1016/j.nbd.2012. 12.016
Mason, B. (2022). Looking back, looking forward: current medications and innovative potential medications to treat alcohol use disorder. ARCR 42, 11. doi: 10.35946/arcr.v42.1.11
NAFDAC (National Agency for Food and Drug Administra-tion and Control) (2024). Press briefing on ban on sachet alcohol. [online] Available at: https://nafdac.gov.ng/press-briefing-on-ban-on-sachet-alcohol/ ([Accessed March 24, 2025).
Nutritionix (2024). Vitamilk Soy Milk. Available at: https://www.nutritionix.com/i/vitamilk/soy-milk/652e6bf0e4 be92000866a90c (Accessed March 30, 2025)
Obernier, J. A., White, A. M., Swartzwelder, H. S., and Crews, F. T. (2002). Cognitive deficits and CNS damage after a 4-day binge ethanol exposure in rats. Pharmacol Biochem Behav 72, 521–532. doi: 10.1016/S0091-3057(02)00715-3
Obrador, E., Salvador-Palmer, R., López-Blanch, R., Jihad-Jebbar, A., Vallés, S. L., and Estrela, J. M. (2021). The link between oxidative stress, redox status, bioenergetics and mitochondria in the pathophysiology of ALS. IJMS 22, 6352. doi: 10.3390/ijms22126352
Odeigah, O. W., and Patton, R. (2024). Alcohol licensing legislation and licensing system in South‐West Nigeria: Implications to regulate physical availability of alcohol. Drug Alcohol Rev 43, 199–212. doi: 10.1111/dar.13767
Okonkwo, T. J. N., Osadebe, P. O., and Proksch, P. (2016). Bioactive phenylpropanoids, phenolic acid and phytosterol from Landolphia owariensis P. Beauv stringy seed pulp: Landolphia owariensis P. Beauv phytochemistry. Phytother Res. 30, 78–83. doi: 10.1002/ptr.5503
Oladeji, O. S., Oluyori, A. P., and Dada, A. O. (2024). Lan-dolphia (P. Beauv.) genus: Ethnobotanical, phytochemical and pharmacological studies. Saudi J Biol Sci 31, 103988. doi: 10.1016/j.sjbs.2024.103988
Oyinbo, C. A., Igbigbi, P. S., and Avwioro, G. O. (2016). Landolphia owariensis attenuates alcohol-induced cerebellar neurodegeneration: significance of neurofilament protein alteration in the Purkinje cells. Folia Medica 58, 241–249. doi: 10.1515/folmed-2016-0034
Oyinbo, C. A., Robert, F. O., Avwioro, O. G., and Igbigbi, P. S. (2018). Jobelyn suppresses hippocampal neuronal apoptosis and necrosis in experimental alcohol-induced brain stress. Pathophysiology 25, 317–325. doi: 10.1016/j.pathophys.2018.05.002
Robert, F. O., and Oyinbo, C. A., (2018). Jobelyn attenuates neuronal degeneration in cerebellar cortex of adolescent rat exposed to binge alcohol. Eur J Biomed 5(2), 109-114.
Robert, F. O., Oyinbo, C. A., Johnbull, T. O., and Atoni, A. D. (2017). Moringa oleifera leaf powder ameriorate neuronal degeneration in the entorhinal cortex of adolescent male alcoholic rats. International Journal of Basic, Applied and Innovative Research 6(4), 107-114.
Sahoo, S. (2018). A review of some medicinal plants used for nervous disorders. J Med Plant Stud 6(3), 220-224.
Singh, A. K., and Bhadra, S. (2022). Alcoholism among adolescents and juvenile delinquency. In Alcoholism. CRC Press, 211-226.
Syahputra, R. A., Sutiani, A., Silitonga, P. M., Rani, Z., and Kudadiri, A. (2021). Extraction and phytochemical screening of ethanol extract and simplicia of moringa leaf (Moringa oleifera Lam.) from sidikalang, north sumatera. International Journal of Science, Technology & Management 2(6), 2072-2076.
Tajuddin, N., Moon, K.-H., Marshall, S. A., Nixon, K., Neaf-sey, E. J., Kim, H.-Y., et al. (2014). Neuroinflammation and neurodegeneration in adult rat brain from binge ethanol exposure: abrogation by docosahexaenoic acid. PLoS ONE 9, e101223. doi: 10.1371/journal.pone.0101223
Tsermpini, E. E., Plemenitaš Ilješ, A., and Dolžan, V. (2022). Alcohol-induced oxidative stress and the role of antioxidants in alcohol use disorder: A systematic review. Antioxidants 11, 1374. doi: 10.3390/antiox11071374
Verkhratsky, A., Butt, A., Li, B., Illes, P., Zorec, R., Semy-anov, A., et al. (2023). Astrocytes in human central nervous system diseases: a frontier for new therapies. Sig Transduct Target Ther 8, 396. doi: 10.1038/s41392-023-01628-9
West, R. K., Rodgers, S. P., and Leasure, J. L. (2021). Neural perturbations associated with recurrent binge alcohol in male and female rats. Alcohol Clin Exp Res 45, 365–374. doi: 10.1111/acer.14529
Yang, C., Liu, G., Chen, X., and Le, W. (2024). Cerebellum in Alzheimer’s disease and other neurodegenerative dis-eases: an emerging research frontier. MedComm 5, e638. doi: 10.1002/mco2.638
Yang, Q., and Zhou, J. (2019). Neuroinflammation in the central nervous system: Symphony of glial cells. Glia 67, 1017–1035. doi: 10.1002/glia.23571
Yuan, A., and Nixon, R. A. (2021). Neurofilament proteins as biomarkers to monitor neurological diseases and the efficacy of therapies. Front Neurosci 15, 689938. doi: 10.3389/fnins.2021.689938
Additional Files
Published
Issue
Section
License
Copyright (c) 2025 Published articles are licensed under Creative Commons Attribution CC BY 4.0, which permits use, sharing, adaptation, distribution, and reproduction in any medium or format, as long as appropriate credit is given to the original author(s) and the source(s).
This work is licensed under a Creative Commons Attribution 4.0 International License.
Copyrights for articles are retained by the authors, with first publication rights granted to the journal. Authors have rights to reuse, republish, archive, and distribute their own articles after publication. The journal/publisher is not responsible for subsequent uses of the work. This journal is licenced under a Creative Commons Attribution 4.0 License CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/).
