Flavonoidlerin Beyin Fonksiyonu Üzerindeki Potansiyellerini Keşfetmek: Üç Fenolik Bileşiğin Beyin Elektriksel Aktivitesi Üzerindeki Etkileri

Öz

Amaç: Organizma tarafından besin zinciri yoluyla alınan en yaygın polifenolik bileşikler flavonoidlerdir. Kan-beyin bariyerini geçtiği bilinen 7,8-DHF, L-theanine ve Fisetin'in nörodejeneratif hastalıklar için terapötik potansiyellerinin yanı sıra nöronal etkilerinin de olduğu bildirilmiştir. Bununla birlikte, nöronal fonksiyon üzerindeki akut etkileri hakkında çok az şey bilinmektedir. Bu çalışma, söz konusu flavonoidlerin sağlıklı farelerin toplam ECoG aktiviteleri ve bant analizleri üzerindeki etkilerini açıklamayı amaçlamaktadır. Materyal ve metod: Bu amaçla her bir flavonoid uygulaması için 7 hayvandan oluşan 3 farklı grup oluşturulmuştur. Bazal elektrofizyolojik kayıtların ardından flavonoid uygulaması yapılmış ve akut etkiler belirlenmiştir. Bulgular: 7.8-DHF, toplam ECoG gücünü düşürürken teta, alfa ve beta bant aktivitelerini artırdı. L-theanine ve Fisetin, toplam ECoG aktivitesini önemli ölçüde değiştirmedi. Bununla birlikte, L-theanine teta, alfa ve beta bant aktivitelerini istatistiksel olarak arttırdı. Sonuç: Sonuç olarak, verilerimiz flavonoidlerin akut ECoG yanıtlarını banda özgü bir şekilde modüle edebildiğini gösterdi. Merkezi sinir sistemi bozuklukları için ilaç keşif çalışmalarında aday moleküller olarak kabul edilebilirler.

Anahtar Kelimeler

• Flavanoidler
• Elektrokortikografi
• Bant aktiviteleri

Exploring the Potentials of Flavonoids on Brain Function: Effects of Three Phenolic Compounds on Brain Electrical Activity

Öz

Background: The most common polyphenolic compounds taken up by the organism through the food chain are flavonoids. Known to cross the blood-brain barrier, 7,8-DHF, L-theanine and Fisetin are re-ported to have neuronal effects as well as therapeutic potential for neurodegenerative diseases. How-ever, little is known on their acute effects of neuronal function. This study aims to describe the effects of the mentioned flavonoids on the total ECoG activities and band analyzes of healthy mice. Materials and Methods: For this purpose, 3 different groups consisting of 7 subjects were created for each flavonoid administration. After the baseline electrophysiological recordings, flavonoid administra-tion was performed and acute effects were determined. Results: 7.8-DHF increased the theta, alpha and beta band activities while decreasing the total ECoG power. L-theanine and Fisetin did not significantly alter the total ECoG activity. However, L-theanine statistically increased theta, alpha and beta band activities. Conclusions: In conclusion, our data showed that flavonoids could acutely modulate the ECoG respons-es in a band specific manner. They can be considered as candidate molecules for drug discovery studies for central nervous system disorders.

Anahtar Kelimeler

• Flavonoids
• Electrocorticography
• band activities

Kaynakça

1. 1. Huyut Z, Beydemir Ş, Gülçin İ. Antioxidant and antiradical properties of selected flavonoids and phenolic compounds. Biochemistry Research International. 2017;1–10. DOI:10.1155/2017/7616791
2. 2. Khan H, Reale M, Ullah H, Sureda A, Tejada S, Wang Y, Zhang Z J, Xiao J. Anti-cancer effects of polyphenols via tar-geting p53 signaling pathway: Updates and future direc-tions. Biotechnology Advances 2020;38: 107385. DOI:10.1016/j. biotechadv.2019.04.007
3. 3. Chaurasia JK, Mishra A, Tripathi YB. Immunomodulation property of hexane fraction of leaves of Cinnamomum ta-mala Linn. 
in rats. Cell Biochem. Funct. 2010, 28, 454–460. 

4. 4. Li Y, Zhou A, Cui X, Zhang Y, Xie J. 6’”-p-Coumaroylspinosin protects PC12 neuronal cells from acrylamide-induced 
oxidative stress and apoptosis. J. Food Biochem. 2020, 44, e13321
5. 5. Maher P. The potential of flavonoids for the treatment of neurodegenerative diseases. Int J Mol Sci. 2019;20:3056.
6. 6. Stockley C, Teissedre P-L, Boban M, Di Lorenzo C, Restani P. Bioavailability of wine-derived phenolic compounds in hu-mans: A review. Food & Function. 2012;3(10): 995–1007. DOI:.1039/c2fo10208k
7. 7. Compaore M, Bakasso S, Meda R, Nacoulma O. Antioxidant and anti-inflammatory activities of fractions from Bidens engleri O.E. Schulz (Asteraceae) and Boerhavia erecta L. (Nyctaginaceae). Medicines. 2018;5(2): 53. DOI:10.3390/medicines5020053
8. 8. Ding S, Xu S, Fang J, Jiang H. The protective effect of poly- phenols for colorectal cancer. Frontiers in Immunology, 2020; 11: 1407. DOI:10.3389/fimmu.2020.01407

9. 9. Schaffer S, Halliwell B. Do polyphenols enter the brain and does it matter? Some theoretical and practical considera-tions. Genes Nutr. 2012; 7: 99–109. 

10. 10. Pal HC, Pearlman RL, Afaq F. Fisetin and its role in choronic diseases. Adv Exp Med Biol. 2016; 928:213-244.
11. 11. Kimira M, Arai Y, Shimoi K, Watanabe S. Japanese intake of flavonoids and isoflavonoids from foods. J Epidemiol. 1998; 8:168-175.
12. 12. Du X, Hill RA. 7,8-Dihydroxyflavone as a pro-neurotrophic treatment for neurodevelopmental disorders. Neurochem Int. 2015; 89:170-180.
13. 13. Luo J, Zhou W, Cao S, Jin m, Zhang C, Jin X, Cui J, Li G. A new biflavonoid from the whole herb of Lepisorus ussuriensis. Nat Prod Res. 2016; 30(13):1470-1476.
14. 14. Wang J, Gao F, Cui S, Yang S, Gao F, Wang X, Zhu G. Utility of 7,8-dihydroxyflavone in preventing astrocytic and synaptic deficits in the hippocampus elicited by PTSD. Pharmacologi-cal Research. 2022; 176:106079.
15. 15. Casimir J, Jadot J, Renard M. Separation and characteriza-tion of N-ethyl-gamma-glutamine from Xerocomus badius. Biochim Biophys Acta. 1960; 39:462-468.
16. 16. Nobre AC, Rao A, Owen GN. L-theanine, a natural constitu-ent in tea, and its effect on mental state. Asia Pac J Clin Nutr. 2008;17(S1):167-168.
17. 17. Rawlings-Mortimer F, Lazari A, Tisca C, Tachrount M, Mar-tins-Bach AB, Miller KL, Lerch JP, Johansen-Berg H. 7,8-dihydroxyflavone enhances long-term spatial memory and alters brain volume in wildtype mice. Systems neurosci-ence. 2023; 1-9.
18. 18. Touil YS, Auzeil N, Boulinguez F, Saighi H, Regazzetti A, Scherman D, Chabot GG. Fisetin disposition and metabolism in mice: identification of geraldol as an active metabolite. Biochemical Pharmacology. 2011; 82:1731-1739.
19. 19. Liu K, Liu E, Lin L, Hu Y, Yuan Y, Xiao W. L-theanine mediates the p38MAPK signaling pathway to alleviate heat-induced axidative stress and inflammation in mice. Food Funct. 2022; 13(4):2120-2130.
20. 20. Feinberg I, Floyd TC, March JD. Effects of sleep loss on delta (0.3-3 Hz) EEG and eye movement density: new observa-tions and hypotheses. Electroencephalogr. Clin. Neuro-physiol.1987; 67:217e221.
21. 21. Gath I, Bar-On E. Classical sleep stages and the spectral content of the EEG signal. Int. J. Neurosci. 1983; 22:147e155.
22. 22. Ktonas PY, Gosalia AP. Spectral analysis vs. period-amplitude analysis of narrowband EEG activity: a compari-son based on the sleep delta-frequency band. Sleep. 1981; 4:193e206.
23. 23. Gaztelu JM, Romero-Vives M, Abraira V, Garcia-Austt E. Hippocampal EEG theta power density is similar during slow-wave sleep and paradoxical sleep. A long-term study in rats. Neurosci. Lett. 1994; 172: 31e34.
24. 24. Reiner M, Rozengurt R, Barnea A, Better than sleep: theta neurofeedback training accelerates memory consolidation. Biol. Psychol. 2014; 95:45e53.
25. 25. Zakrzewska MZ, Brzezicka A. Working memory capacity as a moderator of load-related frontal midline theta variability in Sternberg task. Front. Hum. Neurosci. 2014; 8:399.
26. 26. Ishii R, Canuet L, Ishihara T, Aoki Y, Ikeda S, Hata M, et al. Frontal midline theta rhythm and gamma power changes during focused attention on mental calculation: an MEG beamformer analysis. Front. Hum. Neurosci. 2014; 8:406.
27. 27. Moratti S, Mendez-Bertolo C, Del-Pozo F, Strange BA. Dy-namic gamma frequency feedback coupling between high-er and lower order visual cortices underlies perceptual completion in humans. Neuroimage. 2014; 86:470e479.
28. 28. Suazo V, Diez A, Montes C, Molina V. Structural correlates of cognitive deficit and elevated gamma noise power in schizophrenia. Psychiatry Clin. Neurosci. 2014; 68:206e215.
29. 29. Ozturk H, Basoglu H, Yorulmaz N, Aydin-Abidin S, Abidin I. Fisetin decreases the duration of ictal-like discharges in mouse hippocampal slices. Biol Phys. 2022; 48(3):355-368.
30. 30. Maher P. Preventing and treating neurological disorders with the flavonol fisetin. Brain Plast. 2020; 6(2): 155–166.
31. 31. Das J, Singh R, Ladol S, Nayak SK, Sharma D. Fisetin prevents the aging-associated decline in relative spectral power of α, β and linked MUA in the cortex and behavioral alterations. Experimental Gerontology. 2020; 138:111006.
32. 32. Aydin-Abidin S, Abidin I. 7,8-Dihydroxyflavone potentiates ongoing epileptiform activity in mice brain slices. Neurosci Lett. 2019; 703: 25-31.
33. 33. Faraguna U, Vyazovskiy VV, Nelson AB, Tononi G, Cirelli C. A causal role for brain-derived neurotrophic factor in the ho-meostatic regulation of sleep. J. Neurosci. 2008; 28: 4088e4095.
34. 34. Feng P, Akladious AA, Hu Y, Raslan Y, Feng J, Smith PJ. 7,8-Dihydroxyflavone reduces sleep during dark phase and suppresses orexin A but not orexin B in mice. Journal of Psychiatric Research. 2015; 69:110-119.
35. 35. Akbarialiabad H, Dahroud MD, Khazaei MM, Razmeh S, Zarshenas MM. Green tea, a medicinal food with promising neurological benefits. Current neuropharmacology. 2021; 19:349-359.
36. 36. Abdou AM, Higashiguchi S, Horie K, Kim M, Hatta H, Yoko-goshi H. Relaxation and immunity enhancement effects of gamma-aminobutyric acid (GABA) administration in hu-mans. BioFactors. 2006; 26:201-208.
37. 37. White DJ, de Klerk S, Woods W, Gondalia S, Noonan C, Scholey AB. Anti-stress, behavioural and magnetoenceph-alography effects of an L-theanine-based nutrient drink: a randomized, double-blind, placebo-controlled, crossover trial. Nutrients. 2016; 8:53.
38. 38. Lu K, Gray MA, Oliver C, Liley DT, Harrison BJ, Barthol-omeusz CF, Phan KL, Nathan PJ. The acute effects of L-theanine in comparison with alprazolam on anticipatory anxiety in humans. 
Hum. Psychopharmacol. 2004; 19: 457–465.