Does Umbelliferone Protect Primary Cortical Neuron Cells Against Glutamate Excitotoxicity?

Glutamate is the major excitatory neurotransmitter in the central nervous system. Excessive glutamate is known to cause excitotoxicity.Umbelliferone is a coumarin derivative compound and has antioxidant, anti-infl ammatory, and neuroprotective eff ects. Also, umbelliferone can showneuroprotective eff ect by crossing the blood-brain barrier. In our study, it was aimed to investigate the neuroprotective eff ect of umbelliferone onprimary cortical neuron (PCN) culture. Umbelliferone was isolated from the roots of Ferulago cassia dichloromethane sub-extract. The cerebral cortexof newborn Sprague Dawley rats was used to obtain PCNs. To stimulate glutamate excitotoxicity, cells were exposed to 6x10-5M glutamate. Thendiff erent concentrations (10-1000 μM) of umbelliferone were added into the medium and allowed to incubate for 24 and 72 h. MTT assay was used tomeasure cell viability. Total Antioxidant Status (TAS) and Total Oxidant Status (TOS) analyzes were used to evaluate reactive oxygen species. MTT resultsshowed that cell viability was decreased with glutamate application. 25-250 µM umbelliferone had a significant protective eff ect against glutamateexcitotoxicity at 72 h (P

Umbelliferon, Glutamat Eksitotoksisitesine Karşı Primer Kortikal Nöron Hücrelerini Korur mu?

Glutamat merkezi sinir sisteminin ana uyarıcı nörotransmitteridir. Aşırı glutamatın, glutamat reseptörlerinin uzun süreli aktivasyonu nedeniyle eksitotoksisiteye neden olduğu bilinmektedir. Umbelliferon, antioksidan, antiinfl amatuar ve nöroprotektif etkilere sahip kumarin türevi bir bileşiktir. Ayrıca, umbelliferon kan beyin bariyerini geçerek nöronal hücreleri ölümden koruyabilmektedir. Bu çalışmada glutamat eksitotoksisitesine maruz bırakılan primer kortikal nöron (PCN) kültürlerinde umbelliferonun nöroprotektif etkisinin araştırılması amaçlanmaktadır. Umbelliferon, Ferulago cassia diklorometan alt ekstraktının köklerinden izole edildi. PCN’ler yenidoğan Sprague Dawley cinsi sıçanların serebral kortekslerinden elde edilmiştir. Glutamat eksitotoksistesi oluşturmak için hücreler 6x10-5 M glutamata maruz bırakıldı. Daha sonra hücrelere farklı konsantrasyonlarda (10-1000 μM) umbelliferon uygulanarak 24 ve 72 saat inkübasyona bırakıldı. Hücre canlılık oranı MTT yöntemi ile belirlendi. Hücrelerde oluşan reaktif oksijen türleri Total oxidant status (TOS) ve Total antioxidant status (TAS) yöntemleri ile değerlendirildi. MTT analiz sonuçlarına göre, glutamat uygulaması ile hücre canlılığının azaldığı görüldü. 72. saatte 25-250 µM umbelliferonun glutamat eksitotoksisitesine karşı nöronlarda anlamlı düzeyde koruyucu etkiye sahip olduğu tespit edildi (P

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1. Albright TD, Jessell TM, Kandel ER, Posner MI: Neural science: A century of progress and the mysteries that remain. Neuron, 25, S1-S55, 2000. DOI: 10.1016/s0896-6273(00)80912-5

2. Wen SY, Li AM, Mi KQ, Wang RZ, Li H, Liu HX, Xing Y: In vitro neuroprotective effects of ciliary neurotrophic factor on dorsal root ganglion neurons with glutamate-induced neurotoxicity. Neural Regen Res, 12 (10): 1716-1723, 2017. DOI: 10.4103/1673-5374.217352

3. Howes O, McCutcheon R, Stone J: Glutamate and dopamine in schizophrenia: An update for the 21st century. J Psychopharmacol, 29 (2): 97-115, 2015. DOI: 10.1177/0269881114563634

4. Krebs HA: Metabolism of amino-acids: IV. The synthesis of glutamine from glutamic acid and ammonia, and the enzymic hydrolysis of glutamine in animal tissues. Biochem J, 29 (8): 1951-1969, 1935. DOI: 10.1042/bj0291951

5. Rueda CB, Llorente-Folch I, Traba J, Amigo I, Gonzalez-Sanchez P, Contreras L, Juaristi I, Martinez-Valero P, Pardo B, Del Arco A, Satrustegui J: Glutamate excitotoxicity and Ca2+-regulation of respiration: Role of the Ca2+ activated mitochondrial transporters (CaMCs). Biochim Biophys Acta, 1857 (8): 1158-1166, 2016. DOI: 10.1016/j.bbabio.2016.04.003

6. Hacimuftuoglu A, Tatar A, Cetin D, Taspinar N, Saruhan F, Okkay U, Turkez H, Unal D, Stephens RL, Suleyman H: Astrocyte/neuron ratio and its importance on glutamate toxicity: An in vitro voltammetric study. Cytotechnology, 68 (4): 1425-1433, 2016. DOI: 10.1007/s10616-015-9902-9

7. Schousboe A, Scafidi S, Bak LK, Waagepetersen HS, McKenna MC: Glutamate metabolism in the brain focusing on astrocytes. In, Parpura V, Schousboe A, Verkhratsky A (Eds): Glutamate and ATP at the Interface of Metabolism and Signaling in the Brain.13-30, Springer, Cham, Switzerland, 2014. DOI: 10.1007/978-3-319-08894-5_2

8. Olsen GM, Sonnewald U: Glutamate: Where does it come from and where does it go? Neurochem Int, 88, 47-52, 2015. DOI: 10.1016/j. neuint.2014.11.006

9. Kanamori K: In vivo N-15 MRS study of glutamate metabolism in the rat brain. Anal Biochem, 529, 179-192, 2017. DOI: 10.1016/j.ab.2016.08.025

10. Zhao J, Verwer RWH, Van Wamelen DJ, Qi XR, Gao SF, Lucassen PJ, Swaab DF: Prefrontal changes in the glutamate-glutamine cycle and neuronal/glial glutamate transporters in depression with and without suicide. J Psychiatr Res, 82, 8-15, 2016. DOI: 10.1016/j.jpsychires. 2016.06.017

11. Mahmoud S, Gharagozloo M, Simard C, Gris D: Astrocytes maintain glutamate homeostasis in the CNS by controlling the balance between glutamate uptake and release. Cells, 8 (2): 184, 2019. DOI: 10.3390/ cells8020184

12. Song JH, Kang KS, Choi YK: Protective effect of casuarinin against glutamate-induced apoptosis in HT22 cells through inhibition of oxidative stress-mediated MAPK phosphorylation. Bioorg Med Chem Lett, 27 (23): 5109-5113, 2017. DOI: 10.1016/j.bmcl.2017.10.075

13. Zhao H, Ji ZH, Liu C, Yu XY: Neuroprotective mechanisms of 9-hydroxy epinootkatol against glutamate-induced neuronal apoptosis in primary neuron culture. J Mol Neurosci, 56 (4): 808-814, 2015. DOI: 10.1007/s12031-015-0511-z

14. Jia N, Sun Q, Su Q, Chen G: SIRT1-mediated deacetylation of PGC1α attributes to the protection of curcumin against glutamate excitotoxicity in cortical neurons. Biochem Biophys Res Commun, 478 (3): 1376-1381, 2016. DOI: 10.1016/j.bbrc.2016.08.132

15. Mehta A, Prabhakar M, Kumar P, Deshmukh R, Sharma PL: Excitotoxicity: Bridge to various triggers in neurodegenerative disorders. Eur J Pharmacol, 698 (1-3): 6-18, 2013. DOI: 10.1016/j.ejphar.2012.10.032

16. Floyd RA, Hensley K: Oxidative stress in brain aging: Implications for therapeutics of neurodegenerative diseases. Neurobiol Aging, 23 (5): 795- 807, 2002. DOI: 10.1016/s0197-4580(02)00019-2

17. Anand P, Singh B, Singh N: A review on coumarins as acetylcholinesterase inhibitors for Alzheimer’s disease. Bioorg Med Chem, 20 (3): 1175-1180, 2012. DOI: 10.1016/j.bmc.2011.12.042

18. Adsersen A, Gauguin B, Gudiksen L, Jäger AK: Screening of Research Article 345 DEMİRKAYA, GÜNDOĞDU, KARAKAYA YILMAZ TAŞCI, NALCI, HACIMÜFTÜOĞLU plants used in Danish folk medicine to treat memory dysfunction for acetylcholinesterase inhibitory activity. J Ethnopharmacol, 104 (3): 418- 422, 2006. DOI: 10.1016/j.jep.2005.09.032

19. Tavakoli S, Vatandoost H, Zeidabadinezhad R, Hajiaghaee R, Hadjiakhoondi A, Abai MR, Yassa N: Gas chromatography, GC/Mass analysis and bioactivity of essential oil from aerial parts of Ferulago trifida: Antimicrobial, antioxidant, AChE inhibitory, general toxicity, MTT assay and larvicidal activities. J Arthropod-Borne Dis, 11 (3): 414-426, 2017.

20. Abotsi WK, Ainooson GK, Gyasi EB, Abotsi WKM: Acute and subacute toxicity studies of the ethanolic extract of the aerial parts of Hilleria latifolia (Lam.) H. Walt.(Phytolaccaceae) in rodents. West Afr J Pharm, 22 (1): 27-35, 2011.

21. Vasconcelos JF, Teixeira MM, Barbosa-Filho JM, Agra MF, Nunes XP, Giulietti AM, Ribeiro-Dos-Santos R, Soares MBP: Effects of umbelliferone in a murine model of allergic airway inflammation. Eur J Pharmacol, 609 (1-3): 126-131, 2009. DOI: 10.1016/j.ejphar.2009.03.027

22. Kumar V, Bhatt PC, Rahman M, Al-Abbasi FA, Anwar F, Verma A: Umbelliferon-α-d-glucopyranosyl-(2I →1II)-α-Dglucopyranoside ameliorates Diethylnitrosamine induced precancerous lesion development in liver via regulation of inflammation, hyperproliferation and antioxidant at preclinical stage. Biomed Pharmacother, 94, 834-842, 2017. DOI: 10.1016/j. biopha.2017.07.047

23. Barber SC, Higginbottom A, Mead RJ, Barber S, Shaw PJ: An in vitro screening cascade to identify neuroprotective antioxidants in ALS. Free Radic Biol Med, 46 (8): 1127-1138, 2009. DOI: 10.1016/j. freeradbiomed.2009.01.019

24. Subramaniam SR, Ellis EM: Neuroprotective effects of umbelliferone and esculetin in a mouse model of Parkinson’s disease. J Neurosci Res, 91 (3): 453-461, 2013. DOI: 10.1002/jnr.23164

25. Sundt TM, Anderson RE: Umbelliferone as an Intracellular pH-sensitive fluorescent indicator and blood-brain barrier probe: Instrumentation, calibration, and analysis. J Neurophysiol, 44 (1): 60-75, 1980. DOI: 10.1152/ jn.1980.44.1.60

26. Ali MY, Jannat S, Jung HA, Choi RJ, Roy A, Choi JS: Anti-Alzheimer’s disease potential of coumarins from Angelica decursiva and Artemisia capillaris and structure-activity analysis. Asian Pac J Trop Med, 9 (2): 103- 111, 2016. DOI: 10.1016/j.apjtm.2016.01.014

27. Jayakumar S, Bhilwade H, Chaubey R: Umbelliferone suppresses radiation induced DNA damage and apoptosis in hematopoietic cells of mice. In, Proceedings of the International Conference on Emerging Frontiers and Challenges in Radiation Biology. 24-25 Jan, India, 2012.

28. Vijayalakshmi A, Sindhu G: Data on efficacy of umbelliferone on glycoconjugates and immunological marker in 7, 12-dimethylbenz (a) anthracene induced oral carcinogenesis. Data Brief, 15, 216-221, 2017. DOI: 10.1016/j.dib.2017.09.035

29. Finn GJ, Creaven B, Egan DA: Study of the in vitro cytotoxic potential of natural and synthetic coumarin derivatives using human normal and neoplastic skin cell lines. Melanoma Res, 11 (5): 461-467, 2001. DOI: 10.1097/00008390-200110000-00004

30. Karakaya S, Koca M, Sytar O, Dursunoglu B, Ozbek H, Duman H, Guvenalp Z, Kilic CS: Antioxidant and anticholinesterase potential of Ferulago cassia with farther bio-guided isolation of active coumarin constituents. S Afr J Bot, 121, 536-542, 2019. DOI: 10.1016/j.sajb. 2019.01.020

31. Erel O: A new automated colorimetric method for measuring total oxidant status. Clin Biochem, 38 (12): 1103-1111, 2005. DOI: 10.1016/j. clinbiochem.2005.08.008

32. Erel O: A novel automated method to measure total antioxidant response against potent free radical reactions. Clin Biochem, 37 (2): 112- 119, 2004. DOI: 10.1016/j.clinbiochem.2003.10.014

33.Dwivedi Y, Pandey GN: Glutamatergic neurotransmission abnormalities and schizophrenia. In, Ritsner M (Ed): Handbook of Schizophrenia Spectrum Disorders. 287-304, Springer, Dordrecht, 2011. DOI: 10.1007/ 978-94-007-0837-2_13

34. Michaels RL, Rothman SM: Glutamate neurotoxicity in vitro: Antagonist pharmacology and intracellular calcium concentrations. J Neurosci, 10 (1): 283-292, 1990. DOI: 10.1523/JNEUROSCI.10-01-00283.1990

35. Sasaki-Hamada S, Suzuki A, Sanai E, Matsumoto K, Oka JI: Neuroprotection by chotosan, a Kampo formula, against glutamate excitotoxicity involves the inhibition of GluN2B-, but not GluN2Acontaining NMDA receptor-mediated responses in primary cultured cortical neurons. J Pharmacol Sci, 135 (3): 134-137, 2017. DOI: 10.1016/j. jphs.2017.10.009

36. Coyle JT, Puttfarcken P: Oxidative stress, glutamate, and neurodegenerative disorders. Science, 262 (5134): 689-695, 1993. DOI: 10.1126/ science.7901908

37. Depp C, Bas-Orth C, Schroeder L, Hellwig A, Bading H: Synaptic activity protects neurons against calcium-mediated oxidation and contraction of mitochondria during excitotoxicity. Antioxid Redox Signal, 29 (12): 1109-1124, 2018. DOI: 10.1089/ars.2017.7092

38. Kortagere S, Mortensen OV, Xia J, Lester W, Fang Y, Srikanth Y, Salvino JM, Fontana ACK: Identification of novel allosteric modulators of glutamate transporter EAAT2. ACS Chem Neurosci, 9 (3): 522-534, 2018. DOI: 10.1021/acschemneuro.7b00308

39. Lipton SA, Rosenberg PA: Excitatory amino acids as a final common pathway for neurologic disorders. N Engl J Med, 330 (9): 613-622, 1994. DOI: 10.1056/nejm199403033300907

40. Mazimba O: Umbelliferone: Sources, chemistry and bioactivities review. Bull Fac Pharm Cairo Univ, 55 (2): 223-232, 2017. DOI: 10.1016/j. bfopcu.2017.05.001

41. Sylvester PW: Optimization of the tetrazolium dye (MTT) colorimetric assay for cellular growth and viability. In, Satyanarayanajois S (Ed): Drug Design and Discovery. 157-168, Humana Press, 2011. DOI: 10.1007/978- 1-61779-012-6_9

42. Shen C, Cai GQ, Peng JP, Chen XD: Autophagy protects chondrocytes from glucocorticoids-induced apoptosis via ROS/Akt/FOXO3 signaling. Osteoarthritis Cartilage, 23 (12): 2279-2287, 2015. DOI: 10.1016/j.joca. 2015.06.020

43. Çenesiz S: The role of oxidant and antioxidant parameters in the infectious diseases: A systematic literature review. Kafkas Univ Vet Fak Derg, 26 (6): 849-858, 2020. DOI: 10.9775/kvfd.2020.24618

44. Ghezzi F, Monni L, Corsini S, Rauti R, Nistri A: Propofol protects rat hypoglossal motoneurons in an in vitro model of excitotoxicity by boosting GABAergic inhibition and reducing oxidative stress. Neuroscience, 367, 15-33, 2017. DOI: 10.1016/j.neuroscience.2017.10.019

45. Hara Y, McKeehan N, Dacks PA, Fillit HM: Evaluation of the neuroprotective potential of N-acetylcysteine for prevention and treatment of cognitive aging and dementia. J Prev Alz Dis, 4 (3): 201-206, 2017. DOI: 10.14283/jpad.2017.22

46. Karakaya S, Gözcü S, Güvenalp Z, Özbek H, Yuca H, Dursunoğlu B, Kazaz C, Kılıç CS: The α-amylase and α-glucosidase inhibitory activities of the dichloromethane extracts and constituents of Ferulago bracteata roots. Pharm Biol, 56 (1): 18-24, 2018. DOI: 10.1080/13880209.2017.1414857

47. Fylaktakidou KC, Hadjipavlou-Litina DJ, Litinas KE, Nicolaides DN: Natural and synthetic coumarin derivatives with anti-inflammatory/ antioxidant activities. Curr Pharm Des, 10 (30): 3813-3833, 2004. DOI: 10.2174/1381612043382710

48. Kutlu Z, Celik M, Bilen A, Halıcı Z, Yıldırım S, Karabulut S, Karakaya S, Bostanlık DF, Aydın P: Effects of umbelliferone isolated from the Ferulago pauciradiata Boiss. & Heldr. Plant on cecal ligation and punctureinduced sepsis model in rats. Biomed Pharmacother, 127:110206, 2020. DOI: 10.1016/j.biopha.2020.110206

49. Vijayalakshmi A, Sindhu G: Umbelliferone arrest cell cycle at G0/G1 phase and induces apoptosis in human oral carcinoma (KB) cells possibly via oxidative DNA damage. Biomed Pharmacother, 92, 661-671, 2017. DOI: 10.1016/j.biopha.2017.05.128

50. Germoush MO, Othman SI, Al-Qaraawi MA, Al-Harbi HM, Hussein OE, Al-Basher G, Alotaibi MF, Elgebaly HA, Sandhu MA, Allam AA, Mahmoud AM: Umbelliferone prevents oxidative stress, inflammation and hematological alterations, and modulates glutamate-nitric oxidecGMP signaling in hyperammonemic rats. Biomed Pharmacother, 102, 392-402, 2018. DOI: 10.1016/j.biopha.2018.03.104

51.Hindam MO, Sayed RH, Skalicka-Woźniak K, Budzyńska B, El Sayed NS: Xanthotoxin and umbelliferone attenuate cognitive dysfunction in a streptozotocin-induced rat model of sporadic Alzheimer’s disease: The role of JAK2/STAT3 and Nrf2/HO-1 signalling pathway modulation. Phytother Res, 34 (9): 2351-2365, 2020. DOI: 10.1002/ptr.6686

52. Karakaya S, Koca M, Yılmaz SV, Yıldırım K, Pınar NM, Demirci B, Brestic M, Sytar O: Molecular docking studies of coumarins isolated from extracts and essential oils of zosima absinthifolia link as potential inhibitors for Alzheimer’s disease. Molecules, 24 (4):722, 2019. DOI: 10.3390/molecules24040722
Kafkas Üniversitesi Veteriner Fakültesi Dergisi-Cover
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