Attenuation of Glycoprotein and Hydroxyproline Levels in Sodium Valproate-Induced Brain Damage with Moringa Hydroalcoholic Extracts

Mehraj Babayev; Bertan Boran Bayrak; Umar Faruk Magaji; Özlem Saçan; Refiye Yanardağ

doi:10.26650/EurJBiol.2026.1027253

Attenuation of Glycoprotein and Hydroxyproline Levels in Sodium Valproate-Induced Brain Damage with Moringa Hydroalcoholic Extracts

Abstract

Objective: Valproic acid (VPA) and its salts are psychotropic medications that are widely used to treat neurological diseases, such as epilepsy, migraine, and neuropathic pain, as well as psychiatric disorders, such as schizophrenia, addiction, and bipolar mood disorder. Moringa extract contains antioxidant, antimicrobial, antidiabetic, cardioprotective, and anti-inflammatory compounds that may support human health.

Materials and Methods: This study aimed to investigate the possible protective effects of Moringa hydroalcoholic extract (MOL) against sodium valproate (SVP)-induced damage to brain glycoproteins and hydroxyproline. Female rats (Sprague Dawley) were randomly assigned to the following four groups: control, MOL, SVP, and SVP + MOL. SVP and MOL were administered at doses of 500 and 300 mg/kg body weight, respectively, for 15 days. Rats were sacrificed on day 16. The collection and subsequent homogenisation of brain tissue was conducted using a physiological saline solution at a ratio of 10% (weight/volume). The levels of sialic acid, hexose, hexosamine, fucose, and hydroxyproline were determined in the brain tissue.

Results: Statistical analysis revealed a significant increase in glycoprotein and hydroxyproline levels in the brain tissue of rats treated with SVP. The administration of a hydroalcoholic extract of MOL to rats treated with SVP resulted in the recovery of these alterations, thus preventing or reducing brain damage.

Conclusion: The hydroalcoholic extract of Moringa exerts an attenuating effect on brain damage associated with increased glycoprotein and hydroxyproline levels caused by SVP.

Keywords

References

Rahman M, Awosika AO, Nguyen H. Valproic acid, Treasure Island (FL): StatPearls Publishing, [https://www.ncbi.nlm.nih.gov/books/NBK559112/(accessed](https://www.ncbi.nlm.nih.gov/books/NBK559112/(accessed) on 18 October 2025). google scholar
Schwartz TL, Massa JL, Gupta S, Al-Samarrai S, Devitt P, Masand PS. Divalproex sodium versus valproic acid in hospital treatment of psychotic disorders. Prim Care Companion J Clin Psychiatry, 2000;2(2):45-48.google scholar
Bairy LK, Madhyastha S. Advancements in valproate therapy for seizures, migraines, and bipolar disorders. Med Princ Pract. 2025;34:301-315. google scholar
Bischof MC, Stadelmann MI, Janett S, et al. Valproic acid-associated acute pancreatitis: Systematic literature review. J Clin Med. 2023;12(18):6044. doi:10.3390/jcm12186044 google scholar
Bayrak BB, Sancar S, Cakmak NH, Bolkent S, Yanardag R. Ameliorative effects of edaravone against valproic acid-induced kidney damage. J Mol Histol. 2025;56(1):4. doi:10.1007/s10735-024-10291-5 google scholar
Kadam R, Palkar M, Pingili RB. Mechanisms involved in the valproic acid- induced hepatotoxicity: A comprehensive review. Toxicol Mech Method. 2025;35(6):565-580. google scholar
Magaji UF, Koroglu P, Coremen M, Bulan OK, Sacan O, Yanardag R. Effects of Moringa oleifera extract on biochemical and histological parameters of sodium valproate induced lungs damage. J Mol Histol. 2025;56(1):56. doi:10.1007/ s10735-024-10345-8 google scholar
Terim Kapakin KA, Bolat İ, İskender H, et al. Protective effects of curcumin against valproic acid induced brain kidney and liver damage in rats. Drug Chem Toxicol. 2025;48(3):644-659. google scholar

Chandimali N, Bak SG, Park EH, et al. Free radicals and their impact on health and antioxidant defenses: A review. Cell Death Discov. 2025;11:19. doi:10.1038/ s41420-024-02278-8 google scholar
Xu J, Zhao Y, Tyler Mertens R, Ding Y, Xiao P. Sweet regulation-the emerging immunoregulatory roles of hexoses. J Adv Res. 2025;69:361-379. doi:10.1016/ j.jare.2024.04.014 google scholar
Ter ZY, Mun SL, Abd Rahman NF, et al. A review of glycoproteins in food: Sources, biochemistry and applications. Int J Biol Macromol. 2025;319:145483. doi:10.1016/ j.ijbiomac.2025.145483 google scholar
Kültz D. Molecular and evolutionary basis of the cellular stress response. Ann Rev Physiol. 2005;67:225-257. google scholar
Sharma V, Mahajan G, Gupta R. Nutritional content and renoprotective potential of miracle tree (Moringa oleifera). BioTechnologia. 2025;106(2):223. doi:10.5114/ bta/204529 google scholar
Jain N, Kumari A, Sharma R, Saini V, Jain M. Drumstick tree–an explicable miracle. Emerg Life Sci Res. 2021;7:49-55. google scholar
Nazim M, Raza W, ul Hassan Nasim F, Anjum S, Ullah H, Nawaz A, Ayaz M, Daglia, M. Moringa oleifera: A comprehensive review with special emphasis on phytochemistry. Phytochem Rev. 2026;25:891-944.google scholar
Xie R, Ponnampalam EN, Ahmadi F, Dunshea FR, Suleria HAR. Antioxidant potential and characterization of polyphenol compounds in Moringa oleifera pods. Food Sci Nutr. 2024;12(12):10881-10902. google scholar
Villegas-Vazquez EY, Gómez-Cansino R, Marcelino-Pérez G, Jiménez-López D, Quintas-Granados LI. Unveiling the miracle tree: Therapeutic potential of Moringa oleifera in chronic disease management and beyond. Biomedicines. 2025;13(3):634. doi:10.3390/biomedicines13030634 google scholar
Gao Q, Liu X, Shi J, Li L, Sun B. Polyphenols in different parts of Moringa oleifera Lam.: Composition, antioxidant and neuroprotective potential. Food Chem. 2025;475:143207. doi:10.1016/j.foodchem.2025.143207 google scholar
Alam MN, Singh L, Khan NA, et al. Ameliorative effect of ethanolic extract of Moringa oleifera leaves in combination with curcumin against PTZ-induced kindled epilepsy in rats: In vivo and in silico. Pharmaceuticals (Basel). 2023;16(9):1223. doi:10.3390/ph16091223 google scholar
Soto JA, Gómez AC, Vásquez M, Barreto AN, Molina KS, Zuniga-Gonzalez CA. Biological properties of Moringa oleifera: A systematic review of the last decade. F1000Res. 2025;13:1390. doi:10.12688/f1000research.157194.2 google scholar
Taher MA, Nyeem MAB, Ahammed MM, Hossain MM, Islam MN. Moringa oleifera (Shajna): The wonderful indigenous medicinal plant. Asian J Med Biol Res. 2017;3(1):20-30. google scholar
Ibiyemi FO, Odetayo IK, Adeshina F. Miraculous Moringa: A comprehensive explanation of its botanical, nutritional and medicinal potentials. Int J Res Pharm Allied Sci. 2025;4(7):77-96. google scholar
Bayrak BB, Yanardag R. Histone deacetylase, xanthine oxidase and urease inhibitory activities of Eremurus spectabilis M. Bieb. extracts. Experimed. 2021;11(3):156-161. google scholar
Ertik O, Magaji UF, Sacan O, Yanardag R. Effect of Moringa oleifera leaf extract on valproate-induced oxidative damage in muscle. Drug Chem Toxicol. 2023;46:1212–1222. google scholar
Lorentz K, Weiss T, Kraas E. Sialic acid in human serum and cerebrospinal fluid. Comparison of methods and reference values. J Clin Chem Clin Biochem. 1986;24(3):189–198. google scholar
Winzler RJ. Determination of serum glycoproteins. In: Glick, DP, ed. Methods in Biochemical Analysis. New York, Interscience Publishers Inc., 1955:279–311. google scholar
Zacharias D, Shettles LB. A specific color reaction of methylpentoses and a spectrophotometric micromethod for their determination. J Biol Chem. 1948;175(2):595–603. google scholar
Reddy GK, Enwemeka CS. A simplified method for the analysis of hydroxyproline in biological tissues. Clin Biochem. 1996;29(3):225–229. google scholar
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951;193(1):265–275. google scholar
Cárdenas-Rodríguez N, Carmona-Aparicio L, Pérez-Lozano DL, Ortega-Cuellar D, Gómez-Manzo S, Ignacio-Mejía I. Genetic variations associated with pharmacoresistant epilepsy. Mol Med Rep. 2020;21(4):1685-1701. google scholar
Lv S, Luo C. Blood-brain barrier dysfunction in schizophrenia: Mechanisms and implications. Int J Mol Med. 2025;56(4):153. doi:10.3892/ijmm.2025.5594google scholar
Anandakumar P, Jagan S, Kamaraj S, Ramakrishnan G, Titto AA, Devaki T. Beneficial influence of capsaicin on lipid peroxidation, membrane-bound enzymes and glycoprotein profile during experimental lung carcinogenesis. J Pharm Pharmacol. 2008;60(6):803-808. google scholar
Magaji UF, Miftari S, Saçan Ö, Yanardağ R. Effect of antiepileptic drug sodium valproate on stomach tissue glycoproteins: The protective role of Moringa extract. Arch Epilepsy. 2023;29(2):41-45. European Journal of Biology, 85 (2): 94–101 100Moringa and Sodium Valproate-Induced Brain Damage | Babayev et al., 2026 google scholar
Puigdellívol M, Allendorf DH, Brown GC. Sialylation and galectin-3 in microglia- mediated neuroinflammation and neurodegeneration. Front Cell Neurosci. 2020;14:162. doi:10.3389/fncel.2020.00162google scholar
Iannaccone T, Sellitto C, Manzo V, et al. Pharmacogenetics of carbamazepine and valproate: Focus on polymorphisms of drug metabolizing enzymes and transporters. Pharmaceuticals. 2021;14(3):204. doi:10.3390/ph14030204 google scholar
Zhu W, Zhou Y, Guo L, Feng, S. Biological function of sialic acid and sialylation in human health and disease. Cell Death Discov. 2024;10:415. doi:10.1038/ s41420-024-02180-3 google scholar
Rawal P, Zhao L. Sialometabolism in brain health and Alzheimer’s disease. Front Neurosci. 2021;15:648617. doi:10.3389/fnins.2021.648617 google scholar
Ertik O, Koroglu P, Magaji UF, Bulan NO, Sacan O, Yanardag R. Treatment of oxidative damage caused by valproic acid in tongue tissue with ethanolic Moringa oleifera leaves extract and prediction of potential bioactive molecules with molecular docking. J Mol Histol. 2025;56(1):37. doi:10.1007/ s10735-024-10277-3 google scholar
Guerrero-Flores GN, Butler FM, Martinez Marignac VL, Zhang G, Pacheco FJ, Boskovic DS. Sialic acids in health and disease. Biologics. 2025;5(2):10. doi:10.3390/biologics5020010 google scholar
Pawluczyk IZ, Najafabadi MG, Brown JR, Bevington A, Topham PS. Sialic acid supplementation ameliorates puromycin aminonucleoside nephrosis in rats. Lab Invest. 2015;95(9):1019-1028. google scholar
Yadav J, Verma AK, Garg RK, Ahmad K, Mahdi AA, Srivastava S. Sialic acid associated with oxidative stress and total anti-oxidant capacity (TAC) expression level as a predictive indicator in moderate to severe Alzheimer’s disease. Exp Gerontol. 2020;141:111092. doi:10.1016/j.exger.2020.111092 google scholar
Iijima R, Takahashi H, Namme R, Ikegami S, Yamazaki M. Novel biological function of sialic acid (N‐acetylneuraminic acid) as a hydrogen peroxide scavenger. FEBS Lett. 2004;561(1-3):163-166. google scholar
Gupta A, Prasad B, Singh A. Pharmacological active potential of Moringa oleifera. Int J Agrochem. 2024;10(1):6–12. google scholar
Ozel AB, Cilingir‐Kaya OT, Sener G, et al. Investigation of possible neuroprotective effects of some plant extracts on brain in bile duct ligated rats. J Food Biochem. 2021;45(8):e13835. doi:10.1111/jfbc.13835google scholar
Blanco A, Blanco G. Medical Biochemistry. London, Academic Press; 2017. google scholar
Chen L, Jiang H, Licinio J, Wu H. Brain O-GlcNAcylation: Bridging physiological functions, disease mechanisms, and therapeutic applications. Mol Psychiatry. 2025;30:2754-2772. google scholar
Zou Y, Liu Z, Liu W, Liu Z. Current knowledge and potential intervention of hexosamine biosynthesis pathway in lung cancer. World J Surg Onc. 2023;21(1):334. doi:10.1186/s12957-023-03226-z google scholar
Huang Y, Zhang Z, Chen L. Diagnosis and prognosis of serum Fut8 for epilepsy and refractory epilepsy in children. PLoS One. 2023;18(4):e0284239. doi:10.1371/ journal.pone.0284239 google scholar
Ertik O, Aydin PK, Bulan OK, Yanardag R. Glycoprotein levels and oxidative stomach damage in diabetes and prostate cancer model: Protective effect of metformin. Acta Chim Slov. 2023;70(4):574-587.google scholar
Abe C, Yi Y, Hane M, Kitajima K, Sato C. Acute stress-induced change in polysialic acid levels mediated by sialidase in mouse brain. Sci Rep. 2019;9:9950. doi:10.1038/s41598-019-46240-6 google scholar
Treder, N., Bączek, T. Sialic acid in neurodegenerative and psychiatric disorders: From molecular regulation to targeted nanocarrier-based therapy. Pharmaceutics. 2025;17(12):1593. doi:10.3390/pharmaceutics17121593 google scholar
Dagsuyu E, Koroglu P, Magaji UF, Sacan O, Bulan OK, Yanardag R. Moringa oleifera mitigates oxidative stress and pancreatic toxicity induced by sodium valproate in female Sprague Dawley rats. J Mol Histol. 2025;56(5):325. doi:10.1007/ s10735-025-10600-6 google scholar
Wu G. Important roles of dietary taurine, creatine, carnosine, anserine and 4- hydroxyproline human nutrition and health. Amino Acids. 2020;52:329-360.google scholar
Belostotsky R, Frishberg Y. Catabolism of hydroxyproline in vertebrates: Physiology, evolution, genetic diseases and new siRNA approach for treatment. Int J Mol Sci. 2022;23(2):1005. doi:10.3390/ijms23021005 google scholar
Wu Z, Hou Y, Dai Z, Hu CAA, Wu G. Metabolism, nutrition, and redox signaling of hydroxyproline. Antioxid Redox Signal. 2019;30(4):674-682. google scholar
Srivastava AK, Khare P, Kumar Nagar H, Raghuwanshi N, Srivastava R. Hydroxypoline: A potential biochemical marker and its role in the pathogenesis of different diseases. Curr Protein Pept Sci. 2016;17(6):596-602. google scholar
El-Bakry K, Toson E, Serag M. Hepatoprotective effect of Moringa oleifera leaves extract against carbon tetrachloride-induced liver damage in rats. World J Pharm Pharm Sci. 2016;5:76-89. google scholar
Elik G, Oktay S, Turkyilmaz IB, et al. Dermatoprotective effect of Moringa oleifera leaf extract on sodium valproate-induced skin damage in rats. Drug Chem Toxicol. 2024;47(6):1257-1266. google scholar
Moustafa EM, Abdel-Rafei MK, Thabet NM, Hasan HF. Moringa oleifera leaf ethanolic extract subsidized by low doses of gamma irradiation modulates the thioacetamide induced fibrotic signs in liver of albino rats. Pak J Zool. 2015;47(3):793-802. google scholar

Details

Primary Language

English

Subjects

Toxicology

Journal Section

Research Article

Authors

Mehraj Babayev
0009-0005-7864-5807
Türkiye

Bertan Boran Bayrak ^*
0000-0002-0700-5096
Türkiye

Umar Faruk Magaji
0000-0002-4009-481X
Türkiye

Özlem Saçan
0000-0001-6503-4613
Türkiye

Refiye Yanardağ
0000-0003-4185-4363
Türkiye

Publication Date

June 12, 2026

Submission Date

December 31, 2025

Acceptance Date

February 17, 2026

Published in Issue

Year 2026 Volume: 85 Number: 2

DOI

https://doi.org/10.26650/EurJBiol.2026.1027253

IZ

https://izlik.org/JA84ES36NM

Cite

RIS / Bibtex

APA

Babayev, M., Bayrak, B. B., Magaji, U. F., Saçan, Ö., & Yanardağ, R. (2026). Attenuation of Glycoprotein and Hydroxyproline Levels in Sodium Valproate-Induced Brain Damage with Moringa Hydroalcoholic Extracts. European Journal of Biology, 85(2), 94-101. https://doi.org/10.26650/EurJBiol.2026.1027253

AMA

1.Babayev M, Bayrak BB, Magaji UF, Saçan Ö, Yanardağ R. Attenuation of Glycoprotein and Hydroxyproline Levels in Sodium Valproate-Induced Brain Damage with Moringa Hydroalcoholic Extracts. Eur J Biol. 2026;85(2):94-101. doi:10.26650/EurJBiol.2026.1027253

Chicago

Babayev, Mehraj, Bertan Boran Bayrak, Umar Faruk Magaji, Özlem Saçan, and Refiye Yanardağ. 2026. “Attenuation of Glycoprotein and Hydroxyproline Levels in Sodium Valproate-Induced Brain Damage With Moringa Hydroalcoholic Extracts”. European Journal of Biology 85 (2): 94-101. https://doi.org/10.26650/EurJBiol.2026.1027253.

EndNote

Babayev M, Bayrak BB, Magaji UF, Saçan Ö, Yanardağ R (June 1, 2026) Attenuation of Glycoprotein and Hydroxyproline Levels in Sodium Valproate-Induced Brain Damage with Moringa Hydroalcoholic Extracts. European Journal of Biology 85 2 94–101.

IEEE

[1]M. Babayev, B. B. Bayrak, U. F. Magaji, Ö. Saçan, and R. Yanardağ, “Attenuation of Glycoprotein and Hydroxyproline Levels in Sodium Valproate-Induced Brain Damage with Moringa Hydroalcoholic Extracts”, Eur J Biol, vol. 85, no. 2, pp. 94–101, June 2026, doi: 10.26650/EurJBiol.2026.1027253.

ISNAD

Babayev, Mehraj - Bayrak, Bertan Boran - Magaji, Umar Faruk - Saçan, Özlem - Yanardağ, Refiye. “Attenuation of Glycoprotein and Hydroxyproline Levels in Sodium Valproate-Induced Brain Damage With Moringa Hydroalcoholic Extracts”. European Journal of Biology 85/2 (June 1, 2026): 94-101. https://doi.org/10.26650/EurJBiol.2026.1027253.

JAMA

1.Babayev M, Bayrak BB, Magaji UF, Saçan Ö, Yanardağ R. Attenuation of Glycoprotein and Hydroxyproline Levels in Sodium Valproate-Induced Brain Damage with Moringa Hydroalcoholic Extracts. Eur J Biol. 2026;85:94–101.

MLA

Babayev, Mehraj, et al. “Attenuation of Glycoprotein and Hydroxyproline Levels in Sodium Valproate-Induced Brain Damage With Moringa Hydroalcoholic Extracts”. European Journal of Biology, vol. 85, no. 2, June 2026, pp. 94-101, doi:10.26650/EurJBiol.2026.1027253.

Vancouver

1.Mehraj Babayev, Bertan Boran Bayrak, Umar Faruk Magaji, Özlem Saçan, Refiye Yanardağ. Attenuation of Glycoprotein and Hydroxyproline Levels in Sodium Valproate-Induced Brain Damage with Moringa Hydroalcoholic Extracts. Eur J Biol. 2026 Jun. 1;85(2):94-101. doi:10.26650/EurJBiol.2026.1027253