Vernonia ambigua Alters the Expressions of some Antioxidant Enzymes, Pro-Inflammatory Cytokines, and Acetylcholinesterase in the Cerebellar Cortex of Rats
DOI:
https://doi.org/10.47081/njn2025.16.2/003Keywords:
PCR, Transcriptase, Ethanol leaf-extract, Purkinje cellsAbstract
The therapeutic effects of medicinal plants are often attributed to their recognised and scientifically validated phytochemical constituents. However, literature is rare on the effects of Vernonia ambigua (VA), a documented medicinal plant, on the expression of antioxidant enzymes, cytokines, and neurotransmitters. This study aimed to examine the relative gene expression of cerebellar catalase (rCCAT), glutathione peroxidase-1 (rCGPx-1), tumour necrosis factor-alpha (rCTNF-α), interleukin-1 beta (rCIL-1β), and acetylcholinesterase (rCAChE) in male Wistar rats after the ingestion of an ethanol leaf extract of VA (ELEVA). The 200-220 g rats were divided into four groups, each containing five rats. The control group received feed and water, while test groups ELEVA (E)1, E2, and E3 received 100 mg/kg, 200 mg/kg, and 400 mg/kg of body weight of ELEVA, respectively, for 14 days. On the 15th day, portions of fresh cerebellar tissues were collected for total ribonucleic acid quantification and analysis using a spectrophotometer. Complementary deoxyribonucleic acid was produced using reverse transcriptase kits. rCTNF-α was significantly increased (p<0.05) in E1, E2, and E3, while rCGPx-1 and rCCAT were significantly increased and decreased, respectively, in E3. No significant difference (p>0.05) in rCIL-1β was observed in the test groups. The rCAChE in E1 and E2 were significantly reduced. ELEVA demonstrated concentration-dependent effects that reduced rCCAT and rCAChE but increased rCGPx-1 and rCTNF-α. Consequently, ELEVA may decrease AChE activity, offering potential therapeutic benefits while posing a risk of overstretched inflammatory responses. Additionally, the antioxidant effects of ELEVA may rely on elevated rCGPx-1, as it reduced rCCAT.
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References
Ahn, J. H., Chen, B. H., Shin, B.-N., Lee, T.-K., Cho, J. H., Kim, I. H., et al. (2016). Comparison of catalase immunoreactivity in the hippocampus between young, adult and aged mice and rats. Mol Med Rep 14, 851. doi: 10.3892/mmr.2016.5300
Aliyu, A. B., Musa, A. M., Abdullahi, M. S., Ibrahimi, H., and Oyewale, A. O. (2011). Phytochemical screening and antibacterial activities of Vernonia ambigua, Vernonia blumeoides and Vernonia oocephala (Asteraceae). Acta Pol Pharm 68, 67–73.
Alrafiah, A. (2021). Thymoquinone protects neurons in the cerebellum of rats through mitigating oxidative stress and inflammation following high-fat diet supplementation. Biomolecules 11, 165. doi: 10.3390/biom11020165
Amore, G., Spoto, G., Ieni, A., Vetri, L., Quatrosi, G., Di Rosa, G., et al. (2021). A Focus on the cerebellum: From embryogenesis to an age-related clinical perspective. Front Syst Neurosci 15, 646052. doi: 10.3389/fnsys.2021.646052
Asante, D.-B., Wiafe, G. A., Tsegah, K. M., and Domey, N. K. (2024). Therapeutic Benefits of Vernonia amygdalina in the Treatment of Inflammation and Its Associated Diseases. Clin. Complement Med Pharmacol 4, 100122. doi: 10.1016/j.ccmp.2023.100122
Ashafaq, M., Hussain, S., Alshahrani, S., Siddiqui, R., Alam, M. I., Elhassan Taha, M. M., et al. (2023). Neuroprotective Effects of nano-curcumin against cypermethrin associated oxidative stress and up-regulation of apoptotic and inflammatory gene expression in rat brains. Antioxidants. 12, 644. doi: 10.3390/antiox12030644
Azevedo, F. A. C., Carvalho, L. R. B., Grinberg, L. T., Farfel, J. M., Ferretti, R. E. L., Leite, R. E. P., et al. (2009). Equal numbers of neuronal and nonneuronal cells make the human brain an isometrically scaled‐up primate brain. J Comp Neurol 513, 532–541. doi: 10.1002/cne.21974
Bavarsad, N. H., Bagheri, S., Kourosh-Arami, M., and Komaki, A. (2023). Aromatherapy for the brain: Lavender’s healing effect on epilepsy, depression, anxiety, migraine, and Alzheimer’s disease: A review article. Heliyon 9, e18492. doi: 10.1016/j.heliyon.2023.e18492
Breijyeh, Z., Jubeh, B., Bufo, S. A., Karaman, R., and Scrano, L. (2021). Cannabis: A toxin-producing plant with potential therapeutic uses. Toxins 13, 117. doi: 10.3390/toxins13020117
Brigelius-Flohé, R., and Flohé, L. (2020). Regulatory Phenomena in the Glutathione Peroxidase Superfamily. Antioxid. Redox Signal 33(7), 498-516. doi: 10.1089/ars.2019.7905
Builders, M., Wannang, N., Ajoku, G., Builders, P., Orisadipe, A., and Aguiyi, J. (2011). Evaluation of the Antimalarial Potential of Vernonia ambigua Kotschy and Peyr (Asteraceae). Int J Pharmacol 7, 238–247. doi: 10.3923/ijp.2011.238.247
Caldito, N. G. (2023). Role of tumor necrosis factor-alpha in the central nervous system: a focus on autoimmune disorders. Front Immunol 14, 1213448. doi: 10.3389/fimmu. 2023.1213448
Ciapponi, C., Li, Y., Osorio Becerra, D. A., Rodarie, D., Casellato, C., Mapelli, L., et al. (2023). Variations on the theme: focus on cerebellum and emotional processing. Front Syst Neurosci 17, 1185752. doi: 10.3389/fnsys.2023. 1185752
Cueto-Ureña, C., Ramírez-Expósito, M. J., Mayas, M. D., Carrera-González, M. P., Godoy-Hurtado, A., and Martínez-Martos, J. M. (2023). glutathione peroxidase gpx1 to gpx8 genes expression in experimental brain tumors reveals gender-dependent patterns. Genes 14, 1674. doi: 10.3390/genes14091674
D’Ascenzo, M., and Colussi, C. (2025). Oxidative stress and the central nervous system. Antioxidants 14, 110. doi: 10.3390/antiox14010110
Dash, U. C., Bhol, N. K., Swain, S. K., Samal, R. R., Nayak, P. K., Raina, V., et al. (2025). Oxidative stress and inflammation in the pathogenesis of neurological disorders: Mechanisms and implications. Acta Pharm Sin B 15, 15–34. doi: 10.1016/j.apsb.2024.10.004
Gelata, A., Jemal, M., Gershe, S., and Abdissa, N. (2024). Chemical constituents and evaluation of bioactivity of vernonia hymenolepis A. rich root extracts. Biol Med Nat Prod Chem 13, 595–600. doi: 10.14421/biomedich.2024. 132.595-600
Georgewill, O., and Georgewill, U. (2010). Evaluation of the anti-inflammatory activity of extract of Vernonia Amygdalina. Asian Pac J Trop Med 3, 150–151. doi: 10.1016/S1995-7645(10)60057-0
Goschorska, M., Gutowska, I., Baranowska-Bosiacka, I., Piotrowska, K., Metryka, E., Safranow, K., et al. (2018). Influence of acetylcholinesterase inhibitors used in Alzheimer’s disease treatment on the activity of antioxidant enzymes and the concentration of glutathione in THP-1 macrophages under fluoride-induced oxidative stress. Int. J Environ Res Public Health 16, 10. doi: 10.3390/ijerph16010010
Gregory, J., Vengalasetti, Y. V., Bredesen, D. E., and Rao, R. V. (2021). Neuroprotective herbs for the management of Alzheimer’s disease. Biomolecules 11, 543. doi: 10.3390/biom11040543
Haile, F., G/Medhin, M. T., Kifle, Z. D., Dejenie, T. A., and Berhane, N. (2022). Synergetic antibacterial activity of Vernonia auriculifera Hiern and Buddleja polystachya Fresen on selected human pathogenic bacteria. Metab Open 16, 100210. doi: 10.1016/j.metop.2022.100210
Handy, D. E., and Loscalzo, J. (2022). The role of glutathione peroxidase-1 in health and disease. Free Radic Biol Med 188, 146–161. doi: 10.1016/j.freeradbiomed.2022.06. 004
Hariharan, S., and Dharmaraj, S. (2020). Selenium and selenoproteins: it’s role in regulation of inflammation. Inflammopharmacology 28, 667–695. doi: 10.1007/s10787-020-00690-x
Hendrix, J., Nijs, J., Ickmans, K., Godderis, L., Ghosh, M., and Polli, A. (2020). The Interplay between Oxidative Stress, Exercise, and Pain in Health and Disease: Potential Role of Autonomic Regulation and Epigenetic Mechanisms. Antioxidants 9, 1166. doi: 10.3390/antiox9111166
Hewett, S. J., Jackman, N. A., and Claycomb, R. J. (2012). Interleukin-1β in central nervous system injury and repair. Eur J Neurodegener Dis 1, 195.
Hong, Y., Boiti, A., Vallone, D., and Foulkes, N. S. (2024). Reactive oxygen species signaling and oxidative stress: transcriptional regulation and evolution. Antioxidants 13, 312. doi: 10.3390/antiox13030312
Igwe, E. C., Besong, E. E., Esomchi, C. N., Nwofia, J. O., Okoche, M. C., and Onigbo, E. O. (2024). Effects of Vernonia ambigua on testicular histology, selected semen profiles and serum oxidative stress biomarkers of Wistar rats. J Exp Clin Anat 21, 385–392. doi: 10.4314/jeca.v21i2.33
Kavitha, S., Kumar, T. S., Naresh, E., Kalmani, V. H., Bamane, K. D., and Pareek, P. K. (2023). Medicinal plant identification in real-time using deep learning model. SN Comput Sci 5, 73. doi: 10.1007/s42979-023-02398-5
Kiplimo, J. J. (2016). A Review on the biological activity and the triterpenoids from the genus Vernonia (Asteraceae Family). Int Res J Pure Appl Chem 11, 1–14. doi: 10.9734/IRJPAC/2016/25091
Kunle, O., and Egharevba, H. (2009). Preliminary studies on Vernonia ambigua: phytochemical and antimicrobial screening of the whole plant. Ethnobot Leafl 13, 1216–1221.
Lee, K. H., Cha, M., and Lee, B. H. (2020). Neuroprotective Effect of Antioxidants in the Brain. Int J Mol Sci 21, 7152. doi: 10.3390/ijms21197152
Li, C. N., Keay, K. A., Henderson, L. A., and Mychasiuk, R. (2024). Re-examining the mysterious role of the cerebellum in pain. J Neurosci 44, e1538232024. doi: 10.1523/JNEUROSCI.1538-23.2024
Maroyi, A. (2020). Evaluation of pharmacological properties, phytochemistry and medicinal uses of Vernoniastrum ambiguum. Res J Pharm Technol 13, 4715–4719. doi: 10.5958/0974-360X.2020.00830.6
Mbah Ntepe, L. J., Habib, R., Judith Laure, N., Raza, S., Nepovimova, E., Kuca, K., et al. (2020). Oxidative stress and analysis of selected SNPs of ACHE (rs 2571598), BCHE (rs 3495), CAT (rs 7943316), SIRT1 (rs 10823108), GSTP1 (rs 1695), and Gene GSTM1, GSTT1 in Chronic Organophosphates Exposed Groups from Cameroon and Pakistan. Int J Mol Sci 21, 6432. doi: 10.3390/ijms21176432
Muzio, L., Viotti, A., and Martino, G. (2021). Microglia in neuroinflammation and neurodegeneration: From understanding to therapy. Front Neurosci 15, 742065. doi: 10.3389/fnins.2021.742065
Nandi, A., Yan, L.-J., Jana, C. K., and Das, N. (2019). Role of catalase in oxidative stress- and age-associated degenerative diseases. Oxid Med Cell Longev 2019, 9613090. doi: 10.1155/2019/9613090
National Research Council (2011). Guide for the Care and Use of Laboratory Animals. National Research Council (US) Committee for the Update of the Guide for theCare and Use of Laboratory Animals 8th Edn. Washington (DC): National Academies Press (US). Available at: http://www.ncbi.nlm.nih.gov/books/NBK54050/ (Accessed January 1, 2025).
Nnanga, L. S., Ambamba, B. D. A., Ella, F. A., Mandob, D. E., and Ngondi, J. L. (2022). Lipotropic activities of aqueous extract of Vernonia guineensis Benth. in Wistar rats fed high fat diet. BMC Complement Med Ther 22, 117. doi: 10.1186/s12906-022-03602-4
Noumi, E., and Fozi, F. L. (2003). Ethnomedical botany of epilepsy treatment in Fongo-Tongo village, Western Province, Cameroon. Pharm Biol doi: 10.1076/phbi.41.5.330. 15944
OECD (2022). Test No. 425: Acute Oral Toxicity: Up-and-Down Procedure. Paris: Organisation for Economic Co-operation and Development. Available at: https://www.oecd-ilibrary.org/environment/test-no-425-acut e-oral-toxicity-up-and-down-procedure_9789264071049-en (Accessed December 4, 2024).
Oladele, J. O., Oyeleke, O. M., Oladele, O. T., and Olaniyan, M. (2020). Neuroprotective mechanism of Vernonia amygdalina in a rat model of neurodegenerative diseases. Toxicol Rep 7, 1223–1232. doi: 10.1016/j.toxrep.2020.09.005
Oliveira-Silva, J. A. de, Yamamoto, J. U. P., Oliveira, R. B. de, Monteiro, V. C. L., Frangipani, B. J., Kyosen, S. O., et al. (2019). Oxidative stress assessment by glutathione peroxidase activity and glutathione levels in response to selenium supplementation in patients with Mucopolysaccharidosis I, II and VI. Genet Mol Biol 42, 1–8. doi: 10.1590/1678-4685-GMB-2017-0334
Olufunmilayo, E. O., Gerke-Duncan, M. B., and Holsinger, R. M. D. (2023). Oxidative stress and antioxidants in neurodegenerative disorders. Antioxidants 12, 517. doi: 10.3390/antiox12020517
Omotuyi, O. I., Nash, O., Inyang, O. K., Ogidigo, J., Enejoh, O., Okpalefe, O., et al. (2018). Flavonoid-rich extract of Chromolaena odorata modulate circulating GLP-1 in Wistar rats: computational evaluation of TGR5 involvement. 3 Biotech 8, 124. doi: 10.1007/s13205-018-1138-x
Philips, N., Samuel, P., Keller, T., Alharbi, A., Alshalan, S., and Shamlan, S.-A. (2020). Beneficial regulation of cellular oxidative stress effects, and expression of inflammatory, angiogenic, and the extracellular matrix remodeling proteins by 1α,25-Dihydroxyvitamin D3 in a melanoma cell line. Molecules 25, 1164. doi: 10.3390/molecules25051164
Phillips, J. R., Hewedi, D. H., Eissa, A. M., and Moustafa, A. A. (2015). The cerebellum and psychiatric disorders. Front Public Health 3, 66. doi: 10.3389/fpubh.2015.00066
Rabizadeh, F., Mirian, M. S., Doosti, R., Kiani-Anbouhi, R., and Eftekhari, E. (2022). Phytochemical classification of medicinal plants used in the treatment of kidney disease based on traditional persian medicine. Evid -Based Complement Altern Med 2022, 8022599. doi: 10.1155/2022/8022599
Rasheed, Z. (2024). Therapeutic potentials of catalase: Mechanisms, applications, and future perspectives. Int J Health Sci 18, 1–6.
Roostaei, T., Nazeri, A., Sahraian, M. A., and Minagar, A. (2014). The human cerebellum: a review of physiologic neuroanatomy. Neurol Clin 32, 859–869. doi: 10.1016/j.ncl.2014.07.013
Schad, A., Fahimi, H. D., Völkl, A., and Baumgart, E. (2003). Expression of catalase mRNA and protein in adult rat brain: detection by nonradioactive in situ hybridization with signal amplification by catalyzed reporter deposition (ISH-CARD) and immunohistochemistry (IHC)/ immunofluorescence (IF). J. Histochem. Cytochem. Off. J. Histochem. Soc. 51, 751–760. doi: 10.1177/002215540305100 606
Shim, H. G., Jang, S.-S., Kim, S. H., Hwang, E. M., Min, J. O., Kim, H. Y., et al. (2018). TNF-α increases the intrinsic excitability of cerebellar Purkinje cells through elevating glutamate release in Bergmann Glia. Sci Rep 8, 11589. doi: 10.1038/s41598-018-29786-9
Theja, D. D., and Nirmala, S. (2024). A review of Vernonia cinerea L. ethno-medicinal uses and pharmacology shows that it could be a useful plant for medical purposes. Intell Pharm 2, 662–671. doi: 10.1016/j.ipha.2023. 11.005
Toyang, N. J., and Verpoorte, R. (2013). A review of the medicinal potentials of plants of the genus Vernonia (Asteraceae). J Ethnopharmacol 146, 681–723. doi: 10.1016/j.jep.2013.01.040
Vasincu, A., Luca, S. V., Charalambous, C., Neophytou, C. M., Skalicka-Woźniak, K., and Miron, A. (2022). LC-HRMS/MS phytochemical profiling of Vernonia kotschyana Sch. Bip. ex Walp.: Potential involvement of highly-oxygenated stigmastane-type saponins in cancer cell viability, apoptosis and intracellular ROS production. South Afr J Bot 144, 83–91. doi: 10.1016/j.sajb.2021.09.003
Vladimir-Knežević, S., Blažeković, B., Kindl, M., Vladić, J., Lower-Nedza, A. D., and Brantner, A. H. (2014). Acetylcholinesterase Inhibitory, Antioxidant and Phytochemical Properties of Selected Medicinal Plants of the Lamiaceae Family. Molecules 19, 767. doi: 10.3390/molecules190 10767
Wang, X., and Michaelis, E. K. (2010). Selective neuronal vulnerability to oxidative stress in the brain. Front Aging Neurosci 2, 12. doi: 10.3389/fnagi.2010.00012
Zhang, P., Duan, L., Ou, Y., Ling, Q., Cao, L., Qian, H., et al. (2023). The cerebellum and cognitive neural networks. Front Hum Neurosci 17, 1197459. doi: 10.3389/fnhum. 2023.1197459
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