Abstract
The aim of this study was determined the effects of Hesperidin (HP) on neuronal damage in brain tissue caused by Experimental allergic encephalomyelitis (EAE), an established model of multiple sclerosis in C57BL/J6 mice. To explore 40 mice were equally divided into four groups: (1) Control, (2) EAE, (3) HP, and (4) HP + EAE. 14 days after induction of EAE with MOG35-55 and pertussis toxin, the mice treated with HP at the doses of 50 mg/kg/day for 7 days subcutaneously. To our results HP treatment prevents the oxidative stress caused by EAE via a decrease in lipid peroxidations and increase in elements of the antioxidant defense systems in brain tissue. Also, EAE elevate the IL-17, express the pro-inflammatory cytokines, and caspase-3-like immunreactivity, show apoptosis, staining in EAE mice brain and increased the incidence of histopathological damage. However, immonohistochemical and histological changes were reversed with HP. Moreover, elevated TNF-α and IL-1β levels, a result of EAE, were decreased in serum and neurological deficits as clinical signs were reversed with HP treatment in EAE mice, given HP. In conclusion, HP treatment effectively prevents oxidative, immunological and histological damage in the brain caused by EAE. It was thought that the beneficial effects of HP are likely a result of its strong antioxidant and anti-inflammatory properties.
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Croxford AL, Kurschus FC, Waisman A (2011) Mouse models for multiple sclerosis: historical facts and future implications. Biochim Biophys Acta 1812:177–183
Ma X, Jiang Y, Wu A, Chen X, Pi R, Liu M, Liu Y (2010) Berberine attenuates experimental autoimmune encephalomyelitis in C57 BL/6 mice. PLoS ONE 5(10):e134–e189. doi:10.1371/journal.pone.0013489
Matute C, Perez-Cerda F (2005) Multiple sclerosis: novel perspectives on newly forming lesions. Trends Neurosci 28(4):173–175
Jiang Y, Zou Y, Chen S, Zhu C, Wu A, Liu Y, Ma L, Zhu D, Ma X, Liu M, Kang Z, Pi R, Peng F, Wang Q, Chen X (2013) The anti-inflammatory effect of donepezil on experimental autoimmune encephalomyelitis in C57 BL/6 mice. Neuropharmacology 73:415–424. doi:10.1016/j.neuropharm.2013.06.023
Feng J, Tao T, Yan W, Chen CS, Qin X (2014) Curcumin inhibits mitochondrial injury and apoptosis from the early stage in EAE mice. Oxid Med Cell Longev 2014:728–751. doi:10.1155/2014/728751
Zeng Y, Song C, Ding X, Ji X, Yi L, Zhu K (2007) Baicalin reduces the severity of experimental autoimmune encephalomyelitis. Braz J Med Biol Res 40(7):1003–1010
Lee DH, Gold R, Linker RA (2012) Mechanisms of oxidative damage in multiple sclerosis and neurodegenerative diseases: therapeutic modulation via fumaric acid esters. Int J Mol Sci 13(9):11783–11803. doi:10.3390/ijms130911783
Murphy MP (2009) How mitochondria produce reactive oxygen species. Biochem 417:1–13
Bentli R, Ciftci O, Cetin A, Unlu M, Basak N, Cay M (2013) Oral administration of hesperidin, a citrus flavonone, in rats counteracts the oxidative stress, the inflammatory cytokine production, and the hepatotoxicity induced by the ingestion of 2,3,7,8- tetrachlorodibenzo-p-dioxin (TCDD). Eur Cytokine Netw 24(2):91–96. doi:10.1684/ecn.2013.0337
Kamisli S, Ciftci O, Kaya K, Cetin A, Kamisli O, Ozcan C (2013) Hesperidin protects brain and sciatic nerve tissues against cisplatin-induced oxidative, histological and electromyographical side effects in rats. Toxicol Ind Health. doi:10.1177/0748233713483192
Ross JA, Kasum CM (2002) Dietary flavonoids: bioavailability, metabolic effects, and safety. Annu Rev Nutr 22:19–34
Oztanir MN, Ciftci O, Cetin A, Aladag MA (2014) Hesperidin attenuates oxidative and neuronal damage caused by global cerebral ischemia/reperfusion in a C57BL/J6 mouse model. Neurol Sci 2014; Mar 28 (Epub ahead of print)
Gaur V, Kumar A (2010) Hesperidin pre-treatment attenuates NO-mediated cerebral ischemic reperfusion injury and memory dysfunction. Pharmacol Rep 62(4):635–648
Youdim KA, Dobbie MS, Kuhnle G, Proteggente AR, Abbott NJ, Rice-Evans C (2003) Interaction between flavonoids and the blood–brain barrier: in vitro studies. J Neurochem 85(1):180–192. doi:10.1046/j.1471-4159.2003.01652.x
Hwang SL, Shih PH, Yen GC (2012) Neuroprotective effects of citrus flavonoids. J Agric Food Chem 60(4):877–885
Fonseca-Kelly Z, Nassrallah M, Uribe J, Khan RS, Dine K, Dutt M, Shindler KS (2012) Resveratrol neuroprotection in a chronic mouse model of multiple sclerosis. Front Neurol 3:84. doi:10.3389/fneur.00084
Shindler KS, Ventura E, Dutt M, Elliott P, Fitzgerald DC, Rostami A (2010) Oral resveratrol reduces neuronal damage in a model of multiple sclerosis. J Neuroophthalmol 30(4):328–339. doi:10.1097/WNO.0b013e3181f7f833
Ciftci O, Ozdemir I, Vardi N, Beytur A, Oguz F (2012) Ameliorating effects of quercetin and chrysin on 2,3,7,8-tetrachlorodibenzo- p-dioxin-induced nephrotoxicity in rats. Toxicol Ind Health 28:947–954
Oguzturk H, Ciftci O, Aydin M, Timurkaan N, Beytur A, Yilmaz F (2012) Ameliorative effects of curcumin against acute cadmium toxicity on male reproductive system in rats. Andrologia 44:243–249
Compston A, Coles A (2008) Multiple sclerosis. Lancet 1502–17:1897. doi:10.1016/S0140-6736(08)61620-7
Murray ED, Buttner EA, Price BH (2012) Depression and psychosis in neurological Practice bradley’s neurology in clinical practice. Philadelphia PA Elsevier/SaundersIn Daroff R, Fenichel G, Jankovic J, Mazziotta J1-4377-0434-4
Compston A, Coles A (2002) Multiple sclerosis. Lancet 359(9313):1221–1231. doi:10.1016/S0140-6736(02)08220-X
Ciftci O, Oztanir MN, Cetin A (2014) Neuroprotective effects of ?-myrcene following global cerebral ischemia/reperfusion-mediated oxidative and neuronal damage in a C57BL/J6 Mouse. Neurochem Res 39(9):1717–1723. doi:10.1007/s11064-014-1365-4
di Penta A, Moreno B, Reix S, Fernandez-Diez B, Villanueva M, Errea O, Escala N, Vandenbroeck K, Comella JX, Villoslada P (2013) Oxidative stress and proinflammatory cytokines contribute to demyelination and axonal damage in a cerebellar culture model of neuroinflammation. PLoS ONE 8(2):e54722. doi:10.1371/journal.pone.0054722
Ljubisavljevic S, Stojanovic I, Pavlovic D, Sokolovic D, Stevanovic I (2011) Aminoguanidine and N-acetyl-cysteine supress oxidative and nitrosative stress in EAE rat brains. Redox Rep 16(4):166–172. doi:10.1179/1351000211Y.0000000007
Sunil AG, Kesavanarayanan KS, Kalaivani P, Sathiya S, Ranju V, Priya RJ, Pramila B, Paul FD, Venkhatesh J, Babu CS (2011) Total oligomeric flavonoids of cyperus rotundus ameliorates neurological deficits, excitotoxicity and behavioral alterations induced by cerebral ischemic-reperfusion injury in rats. Brain Res Bull 84:394–405
Gaur V, Kumar A (2010) Hesperidin pre-treatment attenuates NO-mediated cerebral ischemic reperfusion injury and memory dysfunction. Pharmacol Rep 62(4):635–648
De Paula ML, Rodrigues DH, Teixeira HC, Barsante MM, Souza MA, Ferreira AP (2008) Genistein down-modulates pro-inflammatory cytokines and reverses clinical signs of experimental autoimmune encephalomyelitis. Int Immunopharmacol 8(9):1291–1297. doi:10.1016/j.intimp.2008.05.002
Warford J, Jones QR, Nichols M, Sullivan V, Rupasinghe HP, Robertson GS (2014) The flavonoid-enriched fraction AF4 suppresses neuroinflammation and promotes restorative gene expression in a mouse model of experimental autoimmune encephalomyelitis. J Neuroimmunol 268(1–2):71–83.
Manthey JA (2000) Biological properties of flavonoids pertaining to inflammation. Microcirculation 7(6 Pt 2):S29-34
Coelho RC, Hermsdorff HH, Bressan J (2013) Anti-inflammatory properties of orange juice: possible favorable molecular and metabolic effects. Plant Foods Hum Nutr 68(1):1–10. doi:10.1007/s11130-013-0343-3
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We acknowledge the financial support of IUBAP (Scientific Research Fund of Inonu University) under Grant 2013/205.
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Ciftci, O., Ozcan, C., Kamisli, O. et al. Hesperidin, a Citrus Flavonoid, Has the Ameliorative Effects Against Experimental Autoimmune Encephalomyelitis (EAE) in a C57BL/J6 Mouse Model. Neurochem Res 40, 1111–1120 (2015). https://doi.org/10.1007/s11064-015-1571-8
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DOI: https://doi.org/10.1007/s11064-015-1571-8