Cichorium Endivia ve Urtica Dioica Ekstraktlarının SH-SY5Y Hücrelerinde H2O2 Kaynaklı Strese Karşı Etkisi

Öz

Amaç: Nörodejeneratif hastalıklarda artan hidrojen peroksit (H2O2) üretimi nöronlarda oksidatif strese neden olur ve hasar şiddetli olduğunda geri dönüşümsüz olur ve apoptoz tetiklenir. Son yıllarda nöronları oksidatif stresten korumak için nöroprotektif ve antioksidan özellikler sergileyen fitokimyasallar önem kazanmıştır. Bu nedenle yüksek antioksidan kapasitesine ve anti-apoptotik özelliklere sahip bitkisel ekstraktlar H2O2 indüksiyonuna karşı koruyucu bir strateji sağlayabilmektedir. Bu çalışma, Cichorium endivia sıvı ekstraktının (CEE) ve Urtica dioica sıvı ekstraktının (UDE) SH-SY5Y hücreleri üzerindeki H2O2 indüksiyonuna karşı in vitro etkisini incelemeyi amaçlamaktadır. Yöntem: Bu amaçla hücreler ekstraktlarla muamele edildikten sonra H2O2'ye maruz bırakıldı. Bu ekstraktların nöroprotektif etkisi ve hücre canlılığı XTT yöntemi ile değerlendirildi. Antioksidan aktivite CUPRAC yöntemiyle belirlendi. Son olarak ise apoptotik hücre ölümü ve reaktif oksijen türleri (ROS) düzeyi sırasıyla DAPI ve DCFH-DA ile incelendi. Bulgular: Elde edilen sonuçlar, CEE ve UDE'nin H2O2 kaynaklı toksisiteyi, apoptotik hücre ölümünü ve ROS düzeylerini azaltarak nöroproteksiyon, anti-apoptotik ve antioksidan etkiler üzerinde etkiye sahip olduğunu gösterdi. Sonuç: H2O2 oksidatif hasar yoluyla nöronlarda nörotoksisiteye neden olmaktadır. Bunu önlemek amacıyla yüksek antioksidan aktiviteye sahip geleneksel bitki ekstraktları nöroprotektif bir strateji sağlayabilmektedir. Sonuç olarak in vitro modelde bu bitkisel ekstraktların nöroprotektif etki sergileyebileceği gösterilmiştir.

Anahtar Kelimeler

• Cichorium endivia
• Urtica dioica
• nöroprotektif etki
• nörotoksisite
• oksidatif hasar
• hidrojen peroksit (H2O2)

The Influence of Cichorium Endivia and Urtica Dioica Extracts Against H2O2-Induced Stress in SH-SY5Y Cells

Öz

Aim: In neurodegenerative diseases, increased production of hydrogen peroxide (H2O2) causes oxidative stress in neurons, and when the damage is severe, it is irreversible and apoptosis is induced. In recent years, phytochemicals that exhibit neuroprotective and antioxidant properties to protect neurons from oxidative stress have gained importance. Therefore, herbal extracts with high antioxidant capacity and anti-apoptotic properties may provide a protective strategy against H2O2-induction. This study aims to examine the influence of Cichorium endivia liquid extract (CEE) and Urtica dioica liquid extract (UDE) against H2O2-induction on SH-SY5Y cells in vitro. Method: For this purpose, cells were treated with the extracts and then exposed to H2O2. The neuroprotective effect and cell viability of these extracts were evaluated by XTT method. Antioxidant activity was determined by the CUPRAC method. Finally, the apoptotic cell death and reactive oxygen species (ROS) levels were examined with DAPI and DCFH-DA, respectively. Results: The results obtained showed that CEE and UDE have an influence on neuroprotection, anti-apoptotic, and antioxidant effects by reducing H2O2-induced toxicity, apoptotic cell death, and ROS levels. Conclusion: H2O2 causes neurotoxicity in neurons through oxidative damage. To prevent this, traditional plant extracts with high antioxidant activity can provide a neuroprotective strategy. As a consequence, it was shown in an in vitro model that these herbal extracts could be a neuroprotective effect.

Anahtar Kelimeler

• Cichorium endivia
• Urtica dioica
• neuroprotective effect
• neurotoxicity
• oxidative damage
• hydrogen peroxide (H2O2)

Kaynakça

1. 1. Bianchi VE, Herrera PF, Laura R. Effect of nutrition on neurodegenerative diseases. A systematic review. Nutritional Neuroscience. 2021;24(10):810-834.
2. 2. Brezovakova V, Valachova B, Hanes J, Novak M, Jadhav S. Dendritic cells as an alternate approach for treatment of neurodegenerative disorders. Cellular and Molecular Neurobiology. 2018;38:1207-1214.
3. 3. Santa-Cecília FV, Leite CA, Del-Bel E, Raisman-Vozari R. The neuroprotective effect of doxycycline on neurodegenerative diseases. Neurotoxicity Research. 2019;35:981-986.
4. 4. Ano Y, Takaichi Y, Ohya R, Uchida K, Nakayama H, Takashima A. Tryptophan-tyrosine dipeptide improves tau-related symptoms in tauopathy mice. Nutritional Neuroscience. 2023;26(8):766-777.
5. 5. Yeşilkır Baydar S. Alzheimer hastalığı tedavisi için en kestirme yol: İntranazal yaklaşımlar. Sağlık Bilimlerinde Multidisipliner Araştırmalar-3. 2020.
6. 6. World Alzheimer Report 2023. Alzheimer's Disease International;2023.
7. 7. Rahman MH, Bajgai J, Fadriquela A, et al. Redox effects of molecular hydrogen and its therapeutic efficacy in the treatment of neurodegenerative diseases. Processes. 2021;9(2):308.
8. 8. Jiang T, Sun Q, Chen S. Oxidative stress: A major pathogenesis and potential therapeutic target of antioxidative agents in Parkinson’s disease and Alzheimer’s disease. Progress in Neurobiology. 2016;147:1-19.

9. 9. Clardy J, Walsh C. Lessons from natural molecules. Nature. 2004;432(7019):829-837.
10. 10. Chen B, Zhao J, Zhang R, et al. Neuroprotective effects of natural compounds on neurotoxin-induced oxidative stress and cell apoptosis. Nutritional Neuroscience. 2022;25(5):1078-1099.
11. 11. Solanki I, Parihar P, Parihar MS. Neurodegenerative diseases: From available treatments to prospective herbal therapy. Neurochemistry International. 2016;95:100-108.
12. 12. Singh SK, Srivastav S, Castellani RJ, Plascencia-Villa G, Perry G. Neuroprotective and antioxidant effect of Ginkgo biloba extract against AD and other neurological disorders. Neurotherapeutics. 2019;16:666-674.
13. 13. Ay HF, Yesilkir-Baydar S, Cakir-Koc R. Synthesis characterisation and neuroprotectivity of Silybum marianum extract loaded chitosan nanoparticles. Journal of Microencapsulation. 2023;40(1):29-36.
14. 14. Aktas C, Erboga M, Fidanol Erboga Z, Bozdemir Donmez Y, Topcu B, Gurel A. Protective effects of Urtica dioica L. on experimental testicular ischaemia reperfusion injury in rats. Andrologia. 2017;49(4):e12636.
15. 15. Al-Snafi AE. Medical importance of Cichorium intybus–A review. IOSR Journal of Pharmacy. 2016;6(3):41-56.
16. 16. Janda K, Gutowska I, Geszke-Moritz M, Jakubczyk K. The common cichory (Cichorium intybus L.) as a source of extracts with health-promoting properties—a review. Molecules. 2021;26(6):1814.
17. 17. Mascherpa D, Carazzone C, Marrubini G, Gazzani G, Papetti A. Identification of phenolic constituents in Cichorium endivia var. crispum and var. latifolium salads by high-performance liquid chromatography with diode array detection and electrospray ioniziation tandem mass spectrometry. Journal of Agricultural and Food Chemistry. 2012;60(49):12142-12150.
18. 18. Vajic UJ, Grujic-Milanovic J, Miloradovic Z. et al. Urtica dioica L. leaf extract modulates blood pressure and oxidative stress in spontaneously hypertensive rats. Phytomedicine. 2018;46:39-45.
19. 19. Ghasemi S, Moradzadeh M, Hosseini M, Beheshti F, Sadeghnia HR. Beneficial effects of Urtica dioica on scopolamine-induced memory impairment in rats: Protection against acetylcholinesterase activity and neuronal oxidative damage. Drug and Chemical Toxicology. 2019;42(2):167-175.
20. 20. Yu H, Zhang ZL, Chen J, et al. Carvacrol, a food-additive, provides neuroprotection on focal cerebral ischemia/reperfusion injury in mice. PloS One. 2012;7(3):e33584.
21. 21. Xicoy H, Wieringa B, Martens GJ. The SH-SY5Y cell line in Parkinson’s disease research: a systematic review. Molecular Neurodegeneration. 2017;12:1-11.
22. 22. Karavelioglu Z, Cakir-Koc R. Preparation of chitosan nanoparticles as Ginkgo Biloba extract carrier: In vitro neuroprotective effect on oxidative stress-induced human neuroblastoma cells (SH-SY5Y). International Journal of Biological Macromolecules. 2021;192:675-683.
23. 23. Culmsee C, Zhu C, Landshamer S, et al. Apoptosis-inducing factor triggered by poly (ADP-ribose) polymerase and Bid mediates neuronal cell death after oxygen-glucose deprivation and focal cerebral ischemia. 2005;25(44):10262-10272.
24. 24. Han SM, Kim JM, Park KK, Chang YC, Pak SCJBc, medicine a. Neuroprotective effects of melittin on hydrogen peroxide-induced apoptotic cell death in neuroblastoma SH-SY5Y cells. BMC Complementary and Alternative Medicine. 2014;14:1-8.
25. 25. Ferreira MES, de Vasconcelos AS, da Costa Vilhena T, et al. Oxidative stress in Alzheimer’s disease: Should we keep trying antioxidant therapies? Cellular and Molecular Neurobiology. 2015;35:595-614.
26. 26. Huang WJ, Zhang X, Chen WW. Role of oxidative stress in Alzheimer's disease. Biomedical Reports. 2016;4(5):519-522.
27. 27. Cheignon CM, Tomas M, Bonnefont-Rousselot D, Faller P, Hureau C, Collin F. Oxidative stress and the amyloid beta peptide in Alzheimer’s disease. Redox Biology. 2018;14:450-464.
28. 28. Kumar A, Singh A, Aggarwal A. Therapeutic potentials of herbal drugs for Alzheimer’s disease-An overview. Indian J Exp Biol. 2017;55(2):63-73.
29. 29. Zeng Q, Siu W, Li L, et al. Autophagy in Alzheimer's disease and promising modulatory effects of herbal medicine. Experimental Gerontology. 2019;119:100-110.
30. 30. de Medeiros LM, De Bastiani MA, Rico EP, et al. Cholinergic differentiation of human neuroblastoma SH-SY5Y cell line and its potential use as an in vitro model for Alzheimer’s disease studies. Molecular Neurobiology. 2019;56:7355-7367.
31. 31. Praticò D. Oxidative stress hypothesis in Alzheimer’s disease: A reappraisal. Trends in Pharmacological Sciences. 2008;29(12):609-615.
32. 32. Castellani RJ, Lee HG, Perry G, Smith MA. Antioxidant protection and neurodegenerative disease: The role of amyloid-β and tau. American Journal of Alzheimer's Disease & Other Dementias®. 2006;21(2):126-130.
33. 33. Milton NG. Role of hydrogen peroxide in the aetiology of Alzheimer’s disease: Implications for treatment. Drugs & Aging. 2004;21:81-100.
34. 34. Amer A. Antimicrobial effects of Egyptian local chicory, Cichorium endivia subsp. pumilum. International Journal of Microbiology. 2018;2018.
35. 35. Papetti A, Daglia M, Grisoli P, Dacarro C, Gregotti C, Gazzani G. Anti-and pro-oxidant activity of Cichorium genus vegetables and effect of thermal treatment in biological systems. Food Chemistry. 2006;97(1):157-165.
36. 36. Daneshmand P, Saliminejad K, Shasaltaneh MD, et al. Neuroprotective effects of herbal extract (Rosa canina, Tanacetum vulgare and Urtica dioica) on rat model of sporadic Alzheimer’s disease. Avicenna Journal of Medical Biotechnology. 2016;8(3):120.
37. 37. Toldy A, Atalay M, Stadler K, et al. The beneficial effects of nettle supplementation and exercise on brain lesion and memory in rat. The Journal of Nutritional Biochemistry. 2009;20(12):974-981.