Integrated in vivo and in silico assessment of Rauvolfia vomitoria extract on NMDA receptors in a PTZ-induced seizure model
DOI:
https://doi.org/10.31117/neuroscirn.v9i2.518Keywords:
Alkaloid, Pretreatment, Seizure, Recognition memory, Rauvolfia vomitoriaAbstract
Rauvolfia vomitoria (RV) is recognised for its anti-seizure properties, largely due to its rich alkaloid content. In this study, we evaluated the effect of an aqueous extract of Rauvolfia vomitoria on PTZ-induced seizures in male Wistar rats and used in-silico methods to identify the most promising alkaloid compound for predictive analysis. Male Wistar rats (average weight: 160 g) were divided into four groups (n = 5): saline (control), 25 mg/kg PTZ i.p., 200 mg/kg oral RV pretreatment + 25 mg/kg PTZ i.p., and 40 mg/kg oral carbamazepine pretreatment + 25 mg/kg PTZ i.p. Following treatment, we assessed behaviour via the novel object recognition test (NORT) and evaluated antioxidant enzyme levels, brain electrolyte concentrations, and histomorphology changes. Additionally, we employed molecular docking and pharmacokinetic profiling to assess the drug-like properties of the compounds. NORT results revealed increased exploratory time and a non-significant discrimination index. Antioxidant defences were enhanced, while lipid peroxidation indices showed a non-significant reduction. Major electrolyte concentrations were preserved. Molecular docking identified serpentinine as a high-affinity NMDA receptor ligand, with several other Rauvolfia vomitoria alkaloids exhibiting favourable drug-like properties. Oral pretreatment with Rauvolfia vomitoria mitigates PTZ-induced seizure, potentially through antioxidant modulation and a slight trend towards recognition memory. In-silico analyses highlight Rauvolfia vomitoria alkaloids as promising candidates for further experimental validation.
Downloads
References
Aebi, H. (1984). Catalase in vitro. Methods in Enzymology, 105, 121–126. https://doi.org/10.1016/s0076-6879(84)05016-3
Amole, O. O., Yemitan, O. K., & Oshikoya, K. A. (2009). Anticonvulsant activity of Rauvolfia vomitoria (Afzel). African Journal of Pharmacy and Pharmacology, 3(6), 319-322.
Anwar, H., Khan, Q. U., Nadeem, N., Pervaiz, I., Ali, M., & Cheema, F. F. (2020). Epileptic seizures. Discoveries, 8(2), e110. https://doi.org/10.15190/d.2020.7
Bernardi, R. B., & Barros, H. M. T. (2004). Carbamazepine enhances discriminative memory in a rat model of epilepsy. Epilepsia, 45(11), 1443–1447. https://doi.org/10.1111/j.0013-9580.2004.52403.x
Bitew, M., Desalegn, T., Demissie, T. B., Belayneh, A., Endale, M., & Eswaramoorthy, R. (2021). Pharmacokinetics and drug-likeness of antidiabetic flavonoids: Molecular docking and DFT study. PLoS ONE, 16(12), e0260853. https://doi.org/10.1371/journal.pone.0260853
Cheng, F., Li, W., Zhou, Y., Shen, J., Wu, Z., Liu, G., Lee, P. W., & Tang, Y. (2012). admetSAR: A comprehensive source and free tool for assessment of chemical ADMET properties. Journal of Chemical Information and Modeling, 52(11), 3099–3105. https://doi.org/10.1021/ci300367a
Chipiti, T., Viljoen, A. M., Cordero-Maldonado, M. L., Veale, C. G. L., Van Heerden, F. R., Sandasi, M., Chen, W., Crawford, A. D., & Enslin, G. M. (2021). Anti-seizure activity of African medicinal plants: The identification of bioactive alkaloids from the stem bark of Rauvolfia caffra using an in vivo zebrafish model. Journal of Ethnopharmacology, 279, 114282. https://doi.org/10.1016/j.jep.2021.114282
Daina, A., Michielin, O., & Zoete, V. (2017). SwissADME: A free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Scientific Reports, 7(1), 42717. https://doi.org/10.1038/srep42717
Egunlusi, A. O., & Joubert, J. (2024). NMDA receptor antagonists: Emerging insights into molecular mechanisms and clinical applications in neurological disorders. Pharmaceuticals, 17(5), 639. https://doi.org/10.3390/ph17050639
Ekong, M. B., Bassey, O. O., Ebeh, D. I., Usukuma, G. D., Samuel, D. C., Bassey, R. B., Peter, A. I., Mbadugha, C. C., Okokon, J. E., & Akpanabiatu, M. I. (2024). Rauvolfia vomitoria phenol extract relieves pentylenetetrazol-induced seizures in Swiss mice and protects some temporal lobe structures. Acta Epileptologica, 6(1), 35. https://doi.org/10.1186/s42494-024-00183-2
Ekong, M., Peter, A., Davies, K., Bassey, E., Aquaisua, A., Akpanabiatu, M., & Ekanem, T. (2013). Gongronema latifolium ameliorates Rauwolfia vomitoria induced behavior, biochemicals, and histomorphology of the cerebral cortex. [Conference presentation]. Journal of Neurochemistry, 125(S1), 269. https://doi.org/10.1111/jnc.12186
Glasgow, S. D., McPhedrain, R., Madranges, J. F., Kennedy, T. E., & Ruthazer, E. S. (2019). Approaches and limitations in the investigation of synaptic transmission and plasticity. Frontiers in Synaptic Neuroscience, 11, 20. https://doi.org/10.3389/fnsyn.2019.00020
Guskjolen, A., & Cembrowski, M. S. (2023). Engram neurons: Encoding, consolidation, retrieval, and forgetting of memory. Molecular Psychiatry, 28(8), 3207–3219. https://doi.org/10.1038/s41380-023-02137-5
Harborne, J.B. (1973). Phytochemical methods: A guide to modern techniques of plant analysis (1st ed.). Chapman & Hall.
Hoxhaj, P., Habiya, S. K., Sayabugari, R., Balaji, R., Xavier, R., Ahmad, A., Khanam, M., Kachhadia, M. P., Patel, T., Abdin, Z. U., Haider, A., & Nazir, Z. (2023). Investigating the impact of epilepsy on cognitive function: A narrative review. Cureus, 15(6), e41223. https://doi.org/10.7759/cureus.41223
Kiss, T., Orvos, P., Bánsághi, S., Forgo, P., Jedlinszki, N., Tálosi, L., Hohmann, J., & Csupor, D. (2013). Identification of diterpene alkaloids from Aconitum napellus subsp. firmum and GIRK channel activities of some Aconitum alkaloids. Fitoterapia, 90, 85–93. https://doi.org/10.1016/j.fitote.2013.07.010
Kukuia, K. K. E., Mensah, J. A., Amoateng, P., Osei-Safo, D., Koomson, A. E., Torbi, J., Adongo, D. W., Ameyaw, E. O., Ben, I. O., Amponsah, S. K., Bugyei, K. A., & Asiedu-Gyekye, I. J. (2021). Glycine/NMDA receptor pathway mediates the rapid-onset antidepressant effect of alkaloids from Trichilia monadelpha. Basic and Clinical Neuroscience, 12(3), 395–408. https://doi.org/10.32598/bcn.12.3.2838.1
Leone, M. A., Giussani, G., Nevitt, S. J., Marson, A. G., & Beghi, E. (2021). Immediate antiepileptic drug treatment, versus placebo, deferred, or no treatment for first unprovoked seizure. The Cochrane Database of Systematic Reviews, 2021(5), CD007144. https://doi.org/10.1002/14651858.CD007144.pub3
Lueptow, L. M. (2017). Novel object recognition test for the investigation of learning and memory in mice. Journal of Visualized Experiments, 126, 55718. https://doi.org/10.3791/55718
Misra, H. P., & Fridovich, I. (1972). The role of superoxide anion in the autoxidation of epinephrine and a simple assay for superoxide dismutase. The Journal of Biological Chemistry, 247(10), 3170–3175.
Nandi, A., Yan, L.-J., Jana, C. K., & Das, N. (2019). Role of catalase in oxidative stress- and age-associated degenerative diseases. Oxidative Medicine and Cellular Longevity, 2019, 9613090. https://doi.org/10.1155/2019/9613090
OECD. (2002). Guidance Document on Acute Oral Toxicity Testing. OECD. https://doi.org/10.1787/9789264078413-en
Oghenesuvwe, E. E., Ekene, N. E., & Lotanna, A. D. (2014). Guidelines on dosage calculation and stock solution preparation in experimental animals’ studies. Journal of Natural Sciences Research, 4(18), 100.
Ohkawa, H., Ohishi, N., & Yagi, K. (1979). Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Analytical Biochemistry, 95(2), 351–358. https://doi.org/10.1016/0003-2697(79)90738-3
Parsons, A. L. M., Bucknor, E. M. V., Castroflorio, E., Soares, T. R., Oliver, P. L., & Rial, D. (2022). The interconnected mechanisms of oxidative stress and neuroinflammation in epilepsy. Antioxidants, 11(1), 157. https://doi.org/10.3390/antiox11010157
Perucca, E., Bialer, M., & White, H. S. (2023). New GABA-targeting therapies for the treatment of seizures and epilepsy: I. Role of GABA as a modulator of seizure activity and recently approved medications acting on the GABA system. CNS Drugs, 37(9), 755–779. https://doi.org/10.1007/s40263-023-01027-2
Sanya, E. O., Soladoye, A. O., Desalu, O. O., Kolo, P. M., & Olatunji, L. A. (2016). Antiseizure effects of ketogenic diet on seizures induced with pentylenetetrazole, 4-aminopyridine and strychnine in Wistar rats. Nigerian Journal of Physiological Sciences, 31(2), 115-119.
Shan, T., Zhu, Y., Fan, H., Liu, Z., Xie, J., Li, M., & Jing, S. (2024). Global, regional, and national time trends in the burden of epilepsy, 1990–2019: An age-period-cohort analysis for the global burden of disease 2019 study. Frontiers in Neurology, 15, 1418926. https://doi.org/10.3389/fneur.2024.1418926
Shimada, T., & Yamagata, K. (2018). Pentylenetetrazole-induced kindling mouse model. Journal of Visualized Experiments, 136, 56573. https://doi.org/10.3791/56573
Sofowora, A. (1993). Medicinal Plants and Traditional Medicine in Africa (2nd ed.). Spectrum Books.
Sridhar, S., Khamaj, A., & Asthana, M. K. (2023). Cognitive neuroscience perspective on memory: Overview and summary. Frontiers in Human Neuroscience, 17, 1217093. https://doi.org/10.3389/fnhum.2023.1217093
Trease, G.E. and Evans, W.C. (1989). A textbook of pharmacognosy (13th ed.). Baillière Tindall.
Zhang, Y., Ye, F., Zhang, T., Lv, S., Zhou, L., Du, D., Lin, H., Guo, F., Luo, C., & Zhu, S. (2021). Structural basis of ketamine action on human NMDA receptors. Nature, 596(7871), 301–305. https://doi.org/10.1038/s41586-021-03769-9
Downloads
Published
How to Cite
Issue
Section
Categories
License
Copyright (c) 2026 Baliqis Olukade, Ifabunmi Osonuga, Albert Ogunlade, Daniel Umaru, Solape Bello, Adejoke Memudu, Royhaan Folarin

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
The observations and associated materials published or posted by NeurosciRN are licensed by the authors for use and distribution in accord with the Creative Commons Attribution license CC BY-NC 4.0 international, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.