SH-SY5Y İnsan Hücre Hattı: Hawthorne Berry (Crataegus spp.) Parkinson Hastalığının İn Vitro Modelinde Oluşturulan 6-OHDA Kaynaklı Nörotoksisiteye Karşı Korur

Yıl 2023, , 881 - 889, 05.01.2024

Yeşim Yeni , Ahmet Hacımüftüoğlu

https://doi.org/10.38079/igusabder.1308558

Öz

Amaç: Çalışmada antioksidan ve antiinflamatuar özelliklere sahip olduğu bilinen Hawthorn berry (crataegus spp.) ekstraktın, SH-SY5Y hücrelerinde 6-OHDA ile meydana gelen nörotoksisiteye karşı nöroprotektif etkilerini araştırmayı amaçlanmıştır.
Yöntem: SH-SY5Y hücreleri, 6-OHDA uygulamasından önce iki saat boyunca Hawthorn berry (25, 50, 75 ve 100 μg/mL) ile muamele edildi. Hücreler, in vitro Parkinson hastalığı modelini taklit etmek için 24 saat boyunca 200 uM 6-OHDA’ya maruz bırakıldı. Bir gün sonra, 3-(4,5 Dimetiltiazol-2-il)-2,5-difeniltetrazolyum bromür ve laktat dehidrogenaz tahlilleri ile hücre canlılığı belirlendi. Oksidatif stres tümör nekroz faktör-α, interlökin-1β, süperoksit dismutaz, katalaz, glutatyon, glutatyon peroksidaz, miyeloperoksidaz ve malondialdehit analizleri ile değerlendirildi.
Bulgular: Canlılık oranında Hawthorn berry’nin konsantrasyona bağlı olarak bir artış gösterdiği ve en yüksek konsantrasyonda hücre canlılığı % 94 oranında bulundu (p<0,001). Ayrıca, 6-OHDA SH-SY5Y hücrelerinde laktat dehidrogenaz sızıntısını arttırdı (p<0,001). 6-OHDA tümör nekroz faktör-α, interlökin-1β, miyeloperoksidaz ve malondialdehit artırarak oksidatif stresi şiddetlendirirken (p<0,001), Hawthorn berry ile ön tedavi süperoksit dismutaz, katalaz, glutatyon ve glutatyon peroksidazı artırarak antioksidan kapasite yoluyla 6-OHDA'nın bu toksik etkilerini hafifletti (p<0,05), (p<0,001). Tüm bulgular doğrultusunda Hawthorn berry nöronal hücre ölümünü hafifleterek doza bağlı bir şekilde önledi.
Sonuç: Oksidatif stres üzerindeki etkilerinin yanı sıra nöroprotektif rolü göz önüne alındığında Hawthorn berry, Parkinson hastalığının gelişimini önlemek için potansiyel doğal biyo-ilaç olabilir.

Anahtar Kelimeler

Antioksidan, Hawthorn berry, 6-OHDA, Parkinson hastalığı, SH-SY5Y hücre hattı

The SH-SY5Y Human Cell Line: Hawthorne Berry (Crataegus spp.) Protects against 6-OHDA Induced Neurotoxicity In Vitro Model of Parkinson's Disease

Öz

Aim: We purposed to study the neuroprotective effects of Hawthorn berry (crataegus spp.) extract, which is familiar to have antioxidant and anti-inflammatory features, opposite the neurotoxicity led to by 6-OHDA in SH-SY5Y cells.
Method: SH-SY5Y cells were treated with Hawthorn berry (25-50-75 and 100 μg/mL) for two hours ago 6-OHDA administration. Cells were exposed to 200 µM 6-OHDA for 24 hours to mimic the in vitro Parkinson's disease model. After one day, cell viability was measured by lactate dehydrogenase and 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide analysis. Oxidative stress was evaluated with tumor necrosis factor-α, interleukin-1β, superoxide dismutase, catalase, glutathione, glutathione peroxidase, myeloperoxidase, and malondialdehyde assays.
Results: It was found that the viability rate of Hawthorn berry increased depending on the concentration and the cell viability was 94% at the highest concentration (p<0.001). Also, 6-OHDA raised lactate dehydrogenase leakage in SH-SY5Y cells (p<0.001). While 6-OHDA exacerbated oxidative stress by enhancing tumor necrosis factor-α, interleukin-1β, myeloperoxidase, and malondialdehyde (p<0.001), pretreatment with Hawthorn berry alleviated these toxic effects of 6-OHDA through antioxidant capacity by increasing glutathione peroxidase, superoxide dismutase, catalase and glutathione (p<0.05), (p<0.001). In line with all findings, Hawthorn berry attenuated neuronal cell demise in a dose-dependent manner.
Conclusion: Considering its neuroprotective role as well as its effects on oxidative stress, Hawthorn berry could be a potential natural bio-medicine to prevent the development of Parkinson's disease.

Anahtar Kelimeler

Antioxidant, Hawthorn berry, 6-OHDA, Parkinson’s disease, SH-SY5Y cell line

Kaynakça

• 1. Lee YY, Li MH, Tai CH, Luh JJ. Corticomotor excitability changes associated with freezing of gait in people with parkinson disease. Front Hum Neurosci. 2020;14:190.
• 2. Ascherio A, Schwarzschild MA. The epidemiology of Parkinson’s disease: Risk factors and prevention. The Lancet. Neurology. 2016;15:1257–1272.
• 3. Jayaram S, Krishnamurthy PT. Role of microgliosis, oxidative stress and associated neuroinflammation in the pathogenesis of Parkinson’s disease: The therapeutic role of Nrf2 activators. Neurochem Int. 2021;1(145):105014.
• 4. Bo RX, Li YY, Zhou TT, Chen NH, Yuan YH. The neuroinflammatory role of glucocerebrosidase in Parkinson’s disease. Neuropharmacology. 2022;19:108964.
• 5. Piancone F, Saresella M, La Rosa F, et al. Inflammatory responses to monomeric and aggregated α-synuclein in peripheral blood of Parkinson disease patients. Front Neurosci. 2021;15:639646.
• 6. Dionísio PA, Amaral JD, Rodrigues CM. Oxidative stress and regulated cell death in Parkinson’s disease. Ageing Res Rev. 2021;1(67):101263.
• 7. Sodhi RK, Bansal Y, Singh R, et al. IDO-1 inhibition protects against neuroinflammation, oxidative stress and mitochondrial dysfunction in 6-OHDA induced murine model of Parkinson’s disease. Neurotoxicology. 2021;1(84):184–197.
• 8. Hernandez-Baltazar D, Zavala-Flores LM, Villanueva-Olivo A. The 6-hydroxydopamine model and parkinsonian pathophysiology: Novel findings in an older model. Neurologia. 2017;32:533–539.
• 9. Alrashidi H, Eaton S, Heales S. Biochemical characterization of proliferative and differentiated SH-SY5Y cell line as a model for Parkinson’s disease. Neurochem Int. 2021;1(145):105009.
• 10. Huang XX, Ren Q, Song XY, et al. Seven new sesquineolignans isolated from the seeds of hawthorn and their neuroprotective activities. Fitoterapia. 2018;125:6-12.
• 11. Li C, Wang MH. Anti-inflammatory effect of the water fraction from hawthorn fruit on LPS-stimulated RAW 264.7 cells. Nutrition Research and Practice. 2011;5(2):101–106.
• 12. Niu ZZ, Yan MX, Zhao XL, Jin H, Gong YL. Effect of hawthorn seed extract on the gastrointestinal function of rats with diabetic gastroparesis. S Afr J Bot. 2020;130:448–455.
• 13. Dolatkhani P, Jameie R. Antioxidant poperties and medicinal uses of some crataegus spp. (Hawthorn) including C. Meyeri and C. Pontica Curr. Nutr. Food Sci. 2015;11(2):116-123.
• 14. Ruan WL, Shen SH, Xu Y, Ran N, Zhang H. Mechanistic insights into procyanidins as therapies for Alzheimer’s disease: A review. J Funct Foods. 2021;86-104683.
• 15. Tan JW, Kim MK. Neuroprotective effects of bochanin A against β-amyloid-induced neurotoxicity in PC12 cells via a mitochondrial-dependent apoptosis pathway. Molecules. 2016;21:548.
• 16. Olatunji OJ, Feng Y, Olatunji OO, Tang J, Ouyang Z, Su Z. Cordycepin protects PC12 cells against 6-hydroxydopamine induced neurotoxicity via its antioxidant properties. Biomed Pharmacother. 2016;81:7-14.
• 17. Xu Z, Yang D, Huang X, Huang H. Astragaloside IV protects 6-hydroxydopamine induced SH-SY5Y cell model of Parkinson's disease via activating the JAK2/STAT3 pathway. Front Neurosci. 2021;15:631501.
• 18. Angelova PR, Abramov AY. Role of mitochondrial ROS in the brain: From physiology to neurodegeneration. FEBS Lett. 2018;592:692–702.
• 19. Redza-Dutordoir M, Averill-Bates DA. Activation of apoptosis signalling pathways by reactive oxygen species. Biochim Biophys Acta. 2016;1863:2977–2992.
• 20. Ahiskali I, Ferah Okkay I, Mammadov R, et al. Effect of taxifolin on cisplatin-associated oxidative optic nerve damage in rats. Cutan Ocul Toxicol. 2021;40:1–6.
• 21. Wang HL, Zhang J, Li YP, Dong L, Chen YZ. Potential use of glutathione as a treatment for Parkinson’s disease. Exp Ther Med. 2021;21:1–1.
• 22. Ko YH, Kim SK, Kwon SH, et al. 7, 8, 4′-Trihydroxyisoflavone, a metabolized product of daidzein, attenuates 6-hydroxydopamine-induced neurotoxicity in SH-SY5Y cells. Biomol Ther. 2019;27:363.
• 23. Antunes MS, Goes AT, Boeira SP, Prigol M, Jesse CR. Protective effect of hesperidin in a model of Parkinson’s disease induced by 6-hydroxydopamine in aged mice. Nutrition. 2014;30:1415–1422.
• 24. Porres-Martínez M, González-Burgos E, Carretero ME, Gómez-Serranillos MP. Protective properties of Salvia lavandulifolia Vahl. essential oil against oxidative stress-induced neuronal injury. Food Chem Toxicol. 2015;80:154–162.
• 25. Romuk E, Szczurek W, Nowak P, et al. Effects of propofol on oxidative stress parameters in selected parts of the brain in a rat model of Parkinson disease. Postepy Hig Med Dosw. 2016;70(0):1441-1450.
• 26. Chen G, Liu J, Jiang L, et al. Galangin reduces the loss of dopaminergic neurons in an LPS-evoked model of Parkinson’s disease in rats. Int. J. Mol. Sci. 2018;19(1):12.
• 27. Cheng J, Duan Y, Zhang F, et al. The role of lncRNA TUG1 in the Parkinson disease and its effect on microglial inflammatory response. Neuromolecular Med. 2021;23 (2):327–334.
• 28. Zorov DB, Juhaszova M, Sollott SJ. Mitochondrial reactive oxygen species (ROS) and ROS-induced ROS release. Physiol Rev. 2014;94(3):909-950.
• 29. Cirmi S, Maugeri A, Lombardo GE, et al. A flavonoidrich extract of mandarin juice counteracts 6-OHDAinduced oxidative stress in SH-SY5Y cells and modulates Parkinson-related genes. Antioxidants (Basel). 2021;10(4):539.