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Effects of pomegranate peel extract against glutamate excitotoxicity in rat primary neuron culture

Year 2019, Volume: 16 Issue: 2, 186 - 192, 29.08.2019

Damla Binnetoğlu Muhammed Yayla İrfan Çınar Çağlar Demirbağ Pınar Aksu Kılıçle

https://doi.org/10.35440/hutfd.500521
Cited By: 1

Abstract

Background: Many physiological properties of pomegranate
peel which has a strong antioxidant effect have been shown. We aimed to
investigate the effects of pomegranate peel, a potent antioxidant on the
neurotoxic effect of glutamate, an excitatory neurotransmitter.

Methods: In our study, the newly born rat brain cortex
was used. Pomegranate peel extract were used 200, 300 and 400 mg / ml dose
after 2 hours 6x10-3 and 3x10-3M concentration glutamate
application was performed. After 24 hours of toxicity, viability test, total
oxidant and antioxidant capacity measurements were performed.

Results: Glutamate application significantly reduced
cell viability in increased doses, while pomegranate peel extract revealed the
best neuroprotective effect in high doses. Increased total oxidant capacity due
to toxicity has been significantly improved with pomegranate peel application.
Decreased antioxidant capacity due to glutamate has improved with pomegranate
peel extract. Pomegranate peel extract alone had a proliferative effect when
high doses were applied. The pomegranate peel has demonstrated its
neuroprotective effects by suppressing the proinflammatory cytokine tumor
necrosis factor-α and the expression of apoptotic proteins, caspase 9 and 3.

Conclusion: Pomegranate peel extract inhibited
glutamate-induced neurotoxicity due to its antioxidant, anti-inflammatory and
anti-apoptotic effect.

 











Key
Words: Pomegranate,
Excitotoxicity, Glutamate, Rat

Keywords

Pomegranate Excitotoxicity Glutamate Rat

References

  • Referans1. Gölükcü M, Toker R, Tokgöz H. Hasat zamanının nar suyunun şeker ve organik asit bileşimleri üzerine etkisi. Gıda. 2011; 36(6): 355-341.
  • Referans2. İsmail T, Sestili P, Akthar S. Pomegranate peel and fruit extracts: A review of potential anti-inflammatory and anti-infective effects. Journal of ethnopharmacology. 2012; 143(2): 397-405.
  • Referans3. Topkaya C. Nar kabuğu tozu ilavesinin keklerin besinsel, duyusal ve mikrobiyolojik özelliklerine etkisi. Yüksek lisans tezi, Denizli, Pamukkale Üniversitesi Fen Bilimleri Enstitüsü, 2017.
  • Referans4. Karakaya S ve El SN. Total Phenols and Antioxidant Activities of Some Herbal Teas and In Vitro Bioavailability of Black Tea Polyphenols. GOÜ. Ziraat Fakültesi Dergisi. 2006; 23(1): 1-8.
  • Referans5. Özkan G, Baydar G. A Direct RP-HPLC Determination of Phenolic Compounds in Turkish Red Wines. Akdeniz Üniversitesi Ziraat Fakültesi Dergisi. 2006; 19(2): 229-234.
  • Referans6. Chandra R, Jadhav VT, Shrama J. Global scenario of pomagranate (Punica granatum L.) culture with special reference to India. Fruit Veg Cereal Sci 2010; 4(2): 17–8.
  • Referans7. Nizamlıoğlu NM, Nas S. The phenolic compounds in vegetables and fruit; structures and their importance. Electronic Journal of Food Technologies. 2010; 5(1): 20-35.
  • Referans8. Yıldırım AN, Yıldırım F, Şan B, Polat M, Sesli Y. Variability of phenolic composition and tocopherol content of some commercial Almond cultivars. Journal of Applied Botany and Food Quality. 2016; 89(1): 163-170.
  • Referans9. Negi PS, Jayaprakasha GK, Jena BS. Antioxidant and antimutagenic activities of pomegranate peel extracts. Food Chemistry. 2003; 80(3): 393-397.
  • Referans10. Özkal N, Dinç S. Valuation of The Pomegranate (Punica granatum L.) Peels From The Standpoint of Pharmacy. Ankara Üniversitesi Eczacılık Fakültesi Dergisi. 1993; 22(1): 21-29.
  • Referans11. Aydın ÖF, Kurne A, Karabudak R. MS patogenezinde basamaklar-II:nörodejenerasyonda biyolojik göstergeler, sodyum kanalları ve glutamatın rolü. Türk nöroşirurji dergisi. 2006; 12(2): 98-105.
  • Referans12. Gündoğdu G, Taghizadehghalehjoughi A, Çiçek B, Şenol O, Nalcı KA, Demirkaya AK ve ark. Glutamat Eksitotoksisitesi Oluşturulan Primer Kortikal Nöron Kültürlerinde Parietinin Nöroprotektif Etkisinin İncelenmesi. Atatürk Üniversitesi Vet. Bil. Derg. 2018; 13(2): 165-173.
  • Referans13. Cetin D, Hacimufuoglu A, Tatar A, Turkez H, Togar H. The in vitro protective effect of salicylic acid against paclitaxel and cisplatin-induced neurotoxicity. Cytotechnology. 2016; 68(4): 1361-1367.
  • Referans14. Yayla M, Cetin D, Demirbağ Ç, Kılııçle Aksu P. Nar Kabuğu Ekstresinin Sıçanlarda Paklitakselle İndüklenen Primer Nöron Hasarına Karşı Koruyucu Etkisi. Kafkas J Med Sci 2018; 8(3):149–157.
  • Referans15. Palabiyik SS, Karakus E, Halici Z, Cadirci E, Bayir Y, Ayaz G, Cinar I. The protective effects of carvacrol and thymol against paracetamol–induced toxicity on human hepatocellular carcinoma cell lines (HepG2). Human & Experimental Toxicology. 2016; 35(2): 1252-1263.
  • Referans16. Meldrum BS. Glutamate as a neurotransmitter in the brain: review of physiology and pathology. The Journal of Nutrition. 2000; 130(4): 1007–15.
  • Referans17. Sharma A, Kaur G. Tinospora cordifolia as a potential neuroregenerative candidate against glutamate induced excitotoxicity: an in vitro perspective. BMC Complement Altern Med. 2018; 18(1): 268-271.
  • Referans18. Motor S, Ozturk S, Ozcan O, Gurpinar AB, Can Y, Yüksel R et al. Evaluation of total antioxidant status, total oxidant status and oxidative stress index in patients with alopecia areata. Int J Clin Exp Med. 2014; 7(4): 1089–93.
  • Referans19. Kanatt RS, Chander R, Sharma A. Antioxidant and antimicrobial activity of pomegranate peel extract improves the shelf life of chicken products. International Journal of Food Science & Technology. 2010; 45(2): 216-222.
  • Referans20. Aslan R, Kutlu R, Civi S, Tasyurek E. The correlation of the total antioxidant status (TAS), total oxidant status (TOS) and paraoxonase activity (PON1) with smoking Author links open overlay panel. Clin Biochem. 2014; 47(6): 393-7.
  • Referans21. Abundan M, Çelik M, Almaz V, Geter S, Selek S, Koca B et al. Evaluation of S-100B and Oxidative Status before and after Treatment in Children with Bacterial Meningitis. Klin Derg. 2012; 25(2): 67-70.
  • Referans22. Meloni F. Tumor necrosis factor α. Biological aspects. Gior Itali di Chemi 1989; 40(36): 29–37.40.
  • Referans23. MacEwan D J. TNF ligands and receptors – a matter of life and death. Brit J Pharm 2002; 135(4): 855-5.
  • Referans24. MacEwan D J. TNF receptor subtype signalling: differences and cellular consequences. Cell Sig 2002;14(6): 477–92.
  • Referans25. Binnetoğlu D, Yayla M. Agmatine and Glutamate Induced Primary Neuron Damage: In Vitro Study. International Research Journal of Pharmacy and Medical Sciences. 2018; 2(1): 52-56.
  • Referans26. Takeuchi H1, Jin S, Wang J, Zhang G, Kawanokuchi J, Kuno R, Sonobe Y, Mizuno T, Suzumura A. Tumor necrosis factor-alpha induces neurotoxicity via glutamate release from hemichannels of activated microglia in an autocrine manner. J Biol Chem. 2006; 281(30): 21362-8.
  • Referans27. Soojin P, Jin KS, Jun Yup K, Hwa-Jin S, YoungMi K, Yong CB. Anti-Inflammatory Effects of Pomegranate Peel Extract in THP-1 Cells Exposed to Particulate Matter PM10. Evid Based Complement Alternat Med. 2016; 16(3): 1-11.
  • Referans28. Maressa CM, Jocelem MS, Milena T, Danilo M, Patricia B, Hudson SB et al. Neuroprotective Effects of Pomegranate Peel Extract after Chronic Infusion with Amyloid-β Peptide in Mice. PLoS One. 2016; 11(11): e0166123.
  • Referans29. Tüfekçi MA, Ersoy Tunalı N. Huntington Hastalığında Toksisite Mekanizmaları ve NMDAR-Aracılı Eksitotoksisitede Poliaminlerin Rolü. Turkiye Klinikleri J Med Sci.2012; 32(1): 201-213.
  • Referans30. Shuangyue L, Xiao Z, Meiling S, Tao X, Aimei W. FoxO3a plays a key role in the protective effects of pomegranate peel extract against amikacin-induced ototoxicity. Int J Mol Med. 2017; 40(1): 175-181

Sıçan primer nöron kültüründe glutamat eksitotoksisitesine karşı nar kabuğu ekstresinin etkileri

Year 2019, Volume: 16 Issue: 2, 186 - 192, 29.08.2019

Damla Binnetoğlu Muhammed Yayla İrfan Çınar Çağlar Demirbağ Pınar Aksu Kılıçle

https://doi.org/10.35440/hutfd.500521
Cited By: 1

Abstract

Amaç: Güçlü
bir antioksidan etkiye sahip olan nar kabuğunun pek çok fizyolojik özellikleri
gösterilmiştir. Çalışmamızda eksitatör bir nörotransmitter olan glutamatın
nörotoksik etkisine karşı, güçlü antioksidan olan nar kabuğunun etkilerini
araştırmayı amaçladık.

Materyal ve Metot: Çalışmamızda yeni doğan sıçan beyin korteksi kullanılmıştır. Nar
kabuğu ekstresi 200, 300 ve 400 mg/ml dozunda uygulandıktan 2 saat sonra 6x10-3 ve
3x10-3 M konsantrasyonda glutamat uygulaması gerçekleştirildi.
Toksisite oluşturulduktan 24 saat sonra canlılık testi, total oksidan ve
antioksidan kapasite ölçümleri gerçekleştirildi.

Bulgular:
Glutamat uygulaması artan dozlarda hücre canlılığını önemli ölçüde azaltırken
nar kabuğu ekstresi yüksek dozda en iyi nöroprotektif etkiyi ortaya koymuştur.
Toksisiteye bağlı artan oksidan kapasite nar kabuğu uygulaması ile anlamlı
derecede düzelmiştir. Glutamata bağlı azalan antioksidan kapasite nar kabuğu
ekstresi ile düzelme göstermiştir. Nar kabuğu ekstresi tek başına yüksek doz
uygulandığında proliferatif etki ortaya koymuştur. Nar kabuğu nöroprotektif
etkilerini proinflamatuar sitokin olan tümör nekrozis faktör-α ve apoptotik
proteinler olan caspas 3 ve 9 ekspresyonunu baskılayarak ortaya koymuştur.

Sonuç: Nar
kabuğu ekstresi antioksidan, antiinflamatuar ve anti-apoptotik etkisi ile
glutamata bağlı gelişen nörotoksisiteyi önlemiştir.

 











Anahtar Kelimeler: Nar, Eksitotoksisite, Glutamat, Sıçan

Keywords

Nar Eksitotoksisite Glutamat Sıçan

References

  • Referans1. Gölükcü M, Toker R, Tokgöz H. Hasat zamanının nar suyunun şeker ve organik asit bileşimleri üzerine etkisi. Gıda. 2011; 36(6): 355-341.
  • Referans2. İsmail T, Sestili P, Akthar S. Pomegranate peel and fruit extracts: A review of potential anti-inflammatory and anti-infective effects. Journal of ethnopharmacology. 2012; 143(2): 397-405.
  • Referans3. Topkaya C. Nar kabuğu tozu ilavesinin keklerin besinsel, duyusal ve mikrobiyolojik özelliklerine etkisi. Yüksek lisans tezi, Denizli, Pamukkale Üniversitesi Fen Bilimleri Enstitüsü, 2017.
  • Referans4. Karakaya S ve El SN. Total Phenols and Antioxidant Activities of Some Herbal Teas and In Vitro Bioavailability of Black Tea Polyphenols. GOÜ. Ziraat Fakültesi Dergisi. 2006; 23(1): 1-8.
  • Referans5. Özkan G, Baydar G. A Direct RP-HPLC Determination of Phenolic Compounds in Turkish Red Wines. Akdeniz Üniversitesi Ziraat Fakültesi Dergisi. 2006; 19(2): 229-234.
  • Referans6. Chandra R, Jadhav VT, Shrama J. Global scenario of pomagranate (Punica granatum L.) culture with special reference to India. Fruit Veg Cereal Sci 2010; 4(2): 17–8.
  • Referans7. Nizamlıoğlu NM, Nas S. The phenolic compounds in vegetables and fruit; structures and their importance. Electronic Journal of Food Technologies. 2010; 5(1): 20-35.
  • Referans8. Yıldırım AN, Yıldırım F, Şan B, Polat M, Sesli Y. Variability of phenolic composition and tocopherol content of some commercial Almond cultivars. Journal of Applied Botany and Food Quality. 2016; 89(1): 163-170.
  • Referans9. Negi PS, Jayaprakasha GK, Jena BS. Antioxidant and antimutagenic activities of pomegranate peel extracts. Food Chemistry. 2003; 80(3): 393-397.
  • Referans10. Özkal N, Dinç S. Valuation of The Pomegranate (Punica granatum L.) Peels From The Standpoint of Pharmacy. Ankara Üniversitesi Eczacılık Fakültesi Dergisi. 1993; 22(1): 21-29.
  • Referans11. Aydın ÖF, Kurne A, Karabudak R. MS patogenezinde basamaklar-II:nörodejenerasyonda biyolojik göstergeler, sodyum kanalları ve glutamatın rolü. Türk nöroşirurji dergisi. 2006; 12(2): 98-105.
  • Referans12. Gündoğdu G, Taghizadehghalehjoughi A, Çiçek B, Şenol O, Nalcı KA, Demirkaya AK ve ark. Glutamat Eksitotoksisitesi Oluşturulan Primer Kortikal Nöron Kültürlerinde Parietinin Nöroprotektif Etkisinin İncelenmesi. Atatürk Üniversitesi Vet. Bil. Derg. 2018; 13(2): 165-173.
  • Referans13. Cetin D, Hacimufuoglu A, Tatar A, Turkez H, Togar H. The in vitro protective effect of salicylic acid against paclitaxel and cisplatin-induced neurotoxicity. Cytotechnology. 2016; 68(4): 1361-1367.
  • Referans14. Yayla M, Cetin D, Demirbağ Ç, Kılııçle Aksu P. Nar Kabuğu Ekstresinin Sıçanlarda Paklitakselle İndüklenen Primer Nöron Hasarına Karşı Koruyucu Etkisi. Kafkas J Med Sci 2018; 8(3):149–157.
  • Referans15. Palabiyik SS, Karakus E, Halici Z, Cadirci E, Bayir Y, Ayaz G, Cinar I. The protective effects of carvacrol and thymol against paracetamol–induced toxicity on human hepatocellular carcinoma cell lines (HepG2). Human & Experimental Toxicology. 2016; 35(2): 1252-1263.
  • Referans16. Meldrum BS. Glutamate as a neurotransmitter in the brain: review of physiology and pathology. The Journal of Nutrition. 2000; 130(4): 1007–15.
  • Referans17. Sharma A, Kaur G. Tinospora cordifolia as a potential neuroregenerative candidate against glutamate induced excitotoxicity: an in vitro perspective. BMC Complement Altern Med. 2018; 18(1): 268-271.
  • Referans18. Motor S, Ozturk S, Ozcan O, Gurpinar AB, Can Y, Yüksel R et al. Evaluation of total antioxidant status, total oxidant status and oxidative stress index in patients with alopecia areata. Int J Clin Exp Med. 2014; 7(4): 1089–93.
  • Referans19. Kanatt RS, Chander R, Sharma A. Antioxidant and antimicrobial activity of pomegranate peel extract improves the shelf life of chicken products. International Journal of Food Science & Technology. 2010; 45(2): 216-222.
  • Referans20. Aslan R, Kutlu R, Civi S, Tasyurek E. The correlation of the total antioxidant status (TAS), total oxidant status (TOS) and paraoxonase activity (PON1) with smoking Author links open overlay panel. Clin Biochem. 2014; 47(6): 393-7.
  • Referans21. Abundan M, Çelik M, Almaz V, Geter S, Selek S, Koca B et al. Evaluation of S-100B and Oxidative Status before and after Treatment in Children with Bacterial Meningitis. Klin Derg. 2012; 25(2): 67-70.
  • Referans22. Meloni F. Tumor necrosis factor α. Biological aspects. Gior Itali di Chemi 1989; 40(36): 29–37.40.
  • Referans23. MacEwan D J. TNF ligands and receptors – a matter of life and death. Brit J Pharm 2002; 135(4): 855-5.
  • Referans24. MacEwan D J. TNF receptor subtype signalling: differences and cellular consequences. Cell Sig 2002;14(6): 477–92.
  • Referans25. Binnetoğlu D, Yayla M. Agmatine and Glutamate Induced Primary Neuron Damage: In Vitro Study. International Research Journal of Pharmacy and Medical Sciences. 2018; 2(1): 52-56.
  • Referans26. Takeuchi H1, Jin S, Wang J, Zhang G, Kawanokuchi J, Kuno R, Sonobe Y, Mizuno T, Suzumura A. Tumor necrosis factor-alpha induces neurotoxicity via glutamate release from hemichannels of activated microglia in an autocrine manner. J Biol Chem. 2006; 281(30): 21362-8.
  • Referans27. Soojin P, Jin KS, Jun Yup K, Hwa-Jin S, YoungMi K, Yong CB. Anti-Inflammatory Effects of Pomegranate Peel Extract in THP-1 Cells Exposed to Particulate Matter PM10. Evid Based Complement Alternat Med. 2016; 16(3): 1-11.
  • Referans28. Maressa CM, Jocelem MS, Milena T, Danilo M, Patricia B, Hudson SB et al. Neuroprotective Effects of Pomegranate Peel Extract after Chronic Infusion with Amyloid-β Peptide in Mice. PLoS One. 2016; 11(11): e0166123.
  • Referans29. Tüfekçi MA, Ersoy Tunalı N. Huntington Hastalığında Toksisite Mekanizmaları ve NMDAR-Aracılı Eksitotoksisitede Poliaminlerin Rolü. Turkiye Klinikleri J Med Sci.2012; 32(1): 201-213.
  • Referans30. Shuangyue L, Xiao Z, Meiling S, Tao X, Aimei W. FoxO3a plays a key role in the protective effects of pomegranate peel extract against amikacin-induced ototoxicity. Int J Mol Med. 2017; 40(1): 175-181
There are 30 citations in total.

Details

Primary Language Turkish
Subjects Clinical Sciences
Journal Section Research Article
Authors

Damla Binnetoğlu 0000-0002-7041-7253

Muhammed Yayla This is me 0000-0002-0659-3084

İrfan Çınar 0000-0002-9826-2556

Çağlar Demirbağ 0000-0001-7534-341X

Pınar Aksu Kılıçle 0000-0002-3567-5775

Publication Date August 29, 2019
Submission Date December 21, 2018
Acceptance Date July 22, 2019
Published in Issue Year 2019 Volume: 16 Issue: 2

Cite

Vancouver Binnetoğlu D, Yayla M, Çınar İ, Demirbağ Ç, Aksu Kılıçle P. Sıçan primer nöron kültüründe glutamat eksitotoksisitesine karşı nar kabuğu ekstresinin etkileri. Harran Üniversitesi Tıp Fakültesi Dergisi. 2019;16(2):186-92.

Cited By

The investigation of the possible antigenotoxic in vivo effects of pomegranate(Punica granatum L.) peel extract on mitomycin-C genotoxicity
TURKISH JOURNAL OF VETERINARY AND ANIMAL SCIENCES
https://doi.org/10.3906/vet-1911-79
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Harran Üniversitesi Tıp Fakültesi Dergisi  / Journal of Harran University Medical Faculty