Journal of Semnan University of Medical Sciences
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Outline
Investigating the Effect of Silibinin on Oxidative Stress in Olfactory Ensheathing Cells of Rat Pups
Authors
Abstract
Background: Today, cell therapy is one of the most important therapeutic strategies in the nervous system. Meanwhile, the
transplantation of olfactory ensheathing cells (OECs) has attracted the attention of researchers due to their easy access. Silibinin,
the active substance of Silybum marianum, has various properties, including antioxidant properties.
Objectives: In this study, the antioxidant effects of silibinin on oxidative stress in OEC cells were investigated.
Methods: Olfactory ensheathing cells were extracted from the olfactory mucosa of rat pups and cultured. After determination of
the nature of the cells through immunocytochemistry for p75NTR and S100- markers, different concentrations of 1, 5, 10, 25, 50, 75,
100, and 125 μM of silibinin were prepared and added to the cultured cells. The protective and toxic concentrations of silibinin were
determined by the MTT (Dimethyl thiazyl -5 ,2diphenyltetrazolium bromide) test. Protective (5 and 1 μM) and toxic (50 and 75 μM)
concentrations were added to the cultured cells, and the amount of nitric oxide (NO) and reactive oxygen species (ROS) production
was evaluated by Griess and fluorometry methods, respectively.
Results: The results of immunocytochemistry confirmed that the cultured cells are OECs. MTT results confirmed the cell survival
property of low concentrations of silibinin. Protective concentrations of silibinin prevented the increase in NO and ROS production
in OECs.
Conclusion: The results of this study confirmed the antioxidant properties of low concentrations of silibinin in OECs.
Highlights
References
- 1.Mansergh FC, Wride MA, Rancourt DE. Neurons from stem cells: implications for understanding nervous system development and repair. Biochem Cell Biol. 2000;78(5):613-28. [PubMed ID:11103952].
- 2.Mayeur A, Duclos C, Honore A, Gauberti M, Drouot L, do Rego JC, et al. Potential of olfactory ensheathing cells from different sources for spinal cord repair. PLoS One. 2013;8(4):e62860. [PubMed ID:23638158]. [PubMed Central ID:PMC3634744]. https://doi.org/10.1371/journal.pone.0062860.
- 3.Stamegna JC, Felix MS, Roux-Peyronnet J, Rossi V, Feron F, Gauthier P, et al. Nasal OEC transplantation promotes respiratory recovery in a subchronic rat model of cervical spinal cord contusion. Exp Neurol. 2011;229(1):120-31. [PubMed ID:20633558]. https://doi.org/10.1016/j.expneurol.2010.07.002.
- 4.Radtke C, Aizer AA, Agulian SK, Lankford KL, Vogt PM, Kocsis JD. Transplantation of olfactory ensheathing cells enhances peripheral nerve regeneration after microsurgical nerve repair. Brain Res. 2009;1254:10-7. [PubMed ID:19059220]. https://doi.org/10.1016/j.brainres.2008.11.036.
- 5.Chen J, Bhandar B, Kavdia M. Interaction of ROS and RNS with GSH and GSH/GPX Systems. FASEB J. 2015;29(S1). https://doi.org/10.1096/fasebj.29.1_supplement.636.7.
- 6.Tewari D, Sah AN, Bawari S, Nabavi SF, Dehpour AR, Shirooie S, et al. Role of Nitric Oxide in Neurodegeneration: Function, Regulation, and Inhibition. Curr Neuropharmacol. 2021;19(2):114-26. [PubMed ID:32348225]. [PubMed Central ID:PMC8033982]. https://doi.org/10.2174/1570159X18666200429001549.
- 7.Liu C, Liang MC, Soong TW. Nitric Oxide, Iron and Neurodegeneration. Front Neurosci. 2019;13:114. [PubMed ID:30833886]. [PubMed Central ID:PMC6388708]. https://doi.org/10.3389/fnins.2019.00114.
- 8.Hardingham N, Dachtler J, Fox K. The role of nitric oxide in pre-synaptic plasticity and homeostasis. Front Cell Neurosci. 2013;7:190. [PubMed ID:24198758]. [PubMed Central ID:PMC3813972]. https://doi.org/10.3389/fncel.2013.00190.
- 9.Niforou K, Cheimonidou C, Trougakos IP. Molecular chaperones and proteostasis regulation during redox imbalance. Redox Biol. 2014;2:323-32. [PubMed ID:24563850]. [PubMed Central ID:PMC3926111]. https://doi.org/10.1016/j.redox.2014.01.017.
- 10.Morris G, Berk M, Klein H, Walder K, Galecki P, Maes M. Nitrosative Stress, Hypernitrosylation, and Autoimmune Responses to Nitrosylated Proteins: New Pathways in Neuroprogressive Disorders Including Depression and Chronic Fatigue Syndrome. Mol Neurobiol. 2017;54(6):4271-91. [PubMed ID:27339878]. https://doi.org/10.1007/s12035-016-9975-2.
- 11.Hannibal L. Nitric Oxide Homeostasis in Neurodegenerative Diseases. Curr Alzheimer Res. 2016;13(2):135-49. [PubMed ID:26391043]. https://doi.org/10.2174/1567205012666150921101250.
- 12.Schieber M, Chandel NS. ROS function in redox signaling and oxidative stress. Curr Biol. 2014;24(10):R453-62. [PubMed ID:24845678]. [PubMed Central ID:PMC4055301]. https://doi.org/10.1016/j.cub.2014.03.034.
- 13.Borza LR. A review on the cause-effect relationship between oxidative stress and toxic proteins in the pathogenesis of neurodegenerative diseases. Rev Med Chir Soc Med Nat Iasi. 2014;118(1):19-27. [PubMed ID:24741770].
- 14.Mateen S, Tyagi A, Agarwal C, Singh RP, Agarwal R. Silibinin inhibits human nonsmall cell lung cancer cell growth through cell-cycle arrest by modulating expression and function of key cell-cycle regulators. Mol Carcinog. 2010;49(3):247-58. [PubMed ID:19908243]. [PubMed Central ID:PMC3049548]. https://doi.org/10.1002/mc.20595.
- 15.Hogan FS, Krishnegowda NK, Mikhailova M, Kahlenberg MS. Flavonoid, silibinin, inhibits proliferation and promotes cell-cycle arrest of human colon cancer. J Surg Res. 2007;143(1):58-65. [PubMed ID:17950073]. https://doi.org/10.1016/j.jss.2007.03.080.
- 16.Jain D, Somani R. Silibinin, a bioactive flavanone, prevents the progression of early diabetic nephropathy in experimental type-2 diabetic rats. Int J Green Pharm. 2015;9(2). https://doi.org/10.4103/0973-8258.155060.
- 17.Basiglio CL, Sanchez Pozzi EJ, Mottino AD, Roma MG. Differential effects of silymarin and its active component silibinin on plasma membrane stability and hepatocellular lysis. Chem Biol Interact. 2009;179(2-3):297-303. [PubMed ID:19135039]. https://doi.org/10.1016/j.cbi.2008.12.008.
- 18.Duan S, Guan X, Lin R, Liu X, Yan Y, Lin R, et al. Silibinin inhibits acetylcholinesterase activity and amyloid beta peptide aggregation: a dual-target drug for the treatment of Alzheimer's disease. Neurobiol Aging. 2015;36(5):1792-807. [PubMed ID:25771396]. https://doi.org/10.1016/j.neurobiolaging.2015.02.002.
- 19.Alihosseini T, Azizi M, Abbasi N, Mohammadpour S, Bagheri M. Amelioration of amyloid beta (Abeta(1-40)) neurotoxicity by administration of silibinin; a behavioral and biochemical assessment. Iran J Basic Med Sci. 2023;26(7):791-8. [PubMed ID:37396937]. [PubMed Central ID:PMC10311968]. https://doi.org/10.22038/IJBMS.2023.66831.14665.
- 20.Muthu M, Naroem Chanu S, Kalist S, Prabu M. Defensive role of silibinin against arsenic induced oxidative stress mediated dyslipidemia and neurotoxicity in rats. Int J Pharmacol Toxicol. 2016;4(1):78-88. https://doi.org/10.14419/ijpt.v4i1.5803.
- 21.Wang Q, Zou L, Liu W, Hao W, Tashiro S, Onodera S, et al. Inhibiting NF-kappaB activation and ROS production are involved in the mechanism of silibinin's protection against D-galactose-induced senescence. Pharmacol Biochem Behav. 2011;98(1):140-9. [PubMed ID:21167197]. https://doi.org/10.1016/j.pbb.2010.12.006.
- 22.Azizi M, Farahmandghavi F, Joghataei MT, Zandi M, Imani M, Bakhtiari M, et al. ChABC-loaded PLGA nanoparticles: A comprehensive study on biocompatibility, functional recovery, and axonal regeneration in animal model of spinal cord injury. Int J Pharm. 2020;577:119037. [PubMed ID:31953081]. https://doi.org/10.1016/j.ijpharm.2020.119037.
- 23.Wang M, Li YJ, Ding Y, Zhang HN, Sun T, Zhang K, et al. Silibinin Prevents Autophagic Cell Death upon Oxidative Stress in Cortical Neurons and Cerebral Ischemia-Reperfusion Injury. Mol Neurobiol. 2016;53(2):932-43. [PubMed ID:25561437]. https://doi.org/10.1007/s12035-014-9062-5.
- 24.Galhardi F, Mesquita K, Monserrat JM, Barros DM. Effect of silymarin on biochemical parameters of oxidative stress in aged and young rat brain. Food Chem Toxicol. 2009;47(10):2655-60. [PubMed ID:19647779]. https://doi.org/10.1016/j.fct.2009.07.030.
- 25.Shivani C, Lubhan S, Kedarinath T, Vipul K. Neuroprotective effect of Silibinin against middle cerebral artery occlusion induced focal cerebral ischemia and brain injury in Wistar rats. J Neuroscience Behav Health. 2017;9(1):10-5. https://doi.org/10.5897/jnbh2014.0120.
- 26.Song X, Zhou B, Cui L, Lei D, Zhang P, Yao G, et al. Silibinin ameliorates Abeta(25-35)-induced memory deficits in rats by modulating autophagy and attenuating neuroinflammation as well as oxidative stress. Neurochem Res. 2017;42(4):1073-83. [PubMed ID:28004303]. https://doi.org/10.1007/s11064-016-2141-4.
- 27.Lu P, Mamiya T, Lu LL, Mouri A, Niwa M, Hiramatsu M, et al. Silibinin attenuates amyloid beta(25-35) peptide-induced memory impairments: implication of inducible nitric-oxide synthase and tumor necrosis factor-alpha in mice. J Pharmacol Exp Ther. 2009;331(1):319-26. [PubMed ID:19638571]. https://doi.org/10.1124/jpet.109.155069.
- 28.Jung UJ, Jeon MT, Choi MS, Kim SR. Silibinin attenuates MPP(+)-induced neurotoxicity in the substantia nigra in vivo. J Med Food. 2014;17(5):599-605. [PubMed ID:24660866]. https://doi.org/10.1089/jmf.2013.2926.
Copyright
© 2025, Author(s). This open-access article is available under the Creative Commons Attribution 4.0 (CC BY 4.0) International License (https://creativecommons.org/licenses/by/4.0/), which allows for unrestricted use, distribution, and reproduction in any medium, provided that the original work is properly cited.
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