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Doğal Ürünlerdeki Kynurenik Asit İçeriğinin RP-HPLC-UV ile Belirlenmesine Yönelik Yöntem Doğrulama

Yıl 2024, Cilt: 24 Sayı: 2, 188 - 196, 18.11.2024
https://doi.org/10.31467/uluaricilik.1468749

Öz

Kynurenik asit (KYNA) başta kestane balı olmak üzere ıhlamur ve diğer bazı ballarda bulunan farmakoaktif özelliğe sahip bir metabolittir. KYNA’nın antiinflamatuar ve immünosüpresif fonksiyonu düşünüldüğünde biyolojik yolaklar için çift taraflı bir etkiye sahip olduğu görülebilir. Bu sebeple de önemli bir doğal ürün olan ballardaki miktarının belirlenmesi ve bilinmesi sağlık üzerinde yüksek bir etkiye sahip olabilir. Bu metabolitin hem doğal ürünlerde hem de hayvan dokularında tespitine yönelik çalışmalar devam etmekte olup, hızlı ve kolay uygulanabilir metotların geliştirilmesi önem arz etmektedir. Bu çalışma kapsamında doğal ürünlerin (bal, kestane poleni ve kestane çiçeği) KYNA içeriğinin kantitatif olarak kısa sürede belirlenmesi amacıyla ters faz yüksek performanslı sıvı kromatografisinde ultraviyole dedektörü (RP-HPLC-UV) kullanılarak yeni bir metot geliştirilmiştir. Elde edilen verilere göre LOD ve LOQ değerleri sırasıyla 0,030 µg/mL ve 0,092 µg/mL olarak bulunmuştur. Aynı zamanda KYNA’nın ultra saf su (UPW), %70 EtOH, EtOH ve MeOH çözücülerinde hazırlanmış çözeltileri bu metotta analiz edilmiş ve UPW ‘un en uygun çözücüsü olduğu görülmüştür. Bu araştırmanın bulguları, özellikle kestane balının botanik kökeninin ayırt edilmesinde uygulanması açısından KYNA'nın ölçülmesine önemli ölçüde katkıda bulunabilir.

Kaynakça

  • Adams S, Braidy N, Bessesde A, Brew BJ, Grant R, Teo C, Guillemin GJ. The kynurenine pathway in brain tumor pathogenesis Cancer research 2012; 72(22), 5649-5657, doi.org/10.1158/0008-5472.CAN-12-0549.
  • Alt A, Weiss B, Ogden AM, Knauss JL, Oler J, Ho K, et al. Pharmacological characterization of glutamatergic agonists and antagonists at recombinant human homomeric and heteromeric kainate receptors in vitro Neuropharmacology 2004;46(6), 793-806, doi.org/10.1016/j.neuropharm.2003.11.026.
  • Beretta G, Artali R, Caneva E, Orlandini S, Centini M, Facino RM. Quinoline alkaloids in honey: further analytical (HPLC-DAD-ESI-MS, multidimensional diffusion-ordered NMR spectroscopy), theoretical and chemometric studies Journal of Pharmaceutical and Biomedical Analysis 2009;50(3), 432-439, doi.org/10.1016/j.jpba.2009.05.029.
  • Beretta G, Caneva E, Regazzoni L, Bakhtyari NG, Facino RM. A solid-phase extraction procedure coupled to 1H NMR, with chemometric analysis, to seek reliable markers of the botanical origin of honey Analytica chimica acta 2008;620(1-2), 176-182, doi.org/10.1016/j.aca.2008.05.025.
  • Coşkun ZG, Coşkun F. A Review about Honey Effect on Human Body Journal of Apitherapy and Nature 2022;5(1), 35-68, doi.org/10.35206/jan.963498.
  • Fukushima T, Umino M, Sakamoto T, Onozato M. A review of chromatographic methods for bioactive tryptophan metabolites, kynurenine, kynurenic acid, quinolinic acid, and others, in biological fluids Biomedical Chromatography 2022;36(5), e5308, doi.org/10.1002/bmc.5308.
  • Glavin GB, Pinsky C. Kynurenic acid attenuates experimental ulcer formation and basal gastric acid secretion in rats Research communications in chemical pathology and pharmacology 1989;64(1), 111-119.
  • Hilmas C, Pereira EF, Alkondon M, Rassoulpour A, Schwarcz R, Albuquerque EX. The brain metabolite kynurenic acid inhibits α7 nicotinic receptor activity and increases non-α7 nicotinic receptor expression: physiopathological implications Journal of Neuroscience 2001;21(19), 7463-7473.
  • Kaszaki J, Palásthy Z, Erczes D, Racz A, Torday C, Varga G, et al. Kynurenic acid inhibits intestinal hypermotility and xanthine oxidase activity during experimental colon obstruction in dogs Neurogastroenterology & Motility 2008;20(1), 53-62, doi.org/10.1111/j.1365-2982.2007.00989.x.
  • Kim J, Kim D, Lee S. Quantitative Analysis of Kynurenic Acid in Chestnut Honey from Different Regions and Method Validation Korean Journal of Pharmacognosy 2022;53(2), 111-118.
  • Kuc D, Rahnama M, Tomaszewski T, Rzeski W, Wejksza K, Urbanik-Sypniewska T., et al. Kynurenic acid in human saliva-does it influence oral microflora? Pharmacological Reports 2006;58(3), 393.
  • Kuc D, Zgrajka W, Parada-Turska J, Urbanik-Sypniewska T, Turski WA. Micromolar concentration of kynurenic acid in rat small intestine Amino acids 2008;35, 503-505, doi.org/10.1007/s00726-007-0631-z.
  • Lan-Gan, P., Ai-Guo, T., Xi-ming, M., Xi-bo, L., & Xiang, A. (2009). More rapid and sensitive method for simultaneous determination of tryptophan and kynurenic acid by HPLC. Clinical biochemistry, 42(4-5), 420-425, doi.org/10.1016/j.clinbiochem.2008.11.011.
  • Liebig JV. Über kynurensäure Annalen der Chemie und Pharmacie 1853;86(1), 125-126.
  • Mok MS, Fricker AC, Weil A, Kew JN. Electrophysiological characterisation of the actions of kynurenic acid at ligand-gated ion channels Neuropharmacology 2009;57(3), 242-249, doi.org/10.1016/j.neuropharm.2009.06.003.
  • Moroni F, Russi P, Lombardi G, Beni M, Carla V. Presence of kynurenic acid in the mammalian brain Journal of neurochemistry 1988;51(1), 177-180, doi.org/10.1111/j.1471-4159.1988.tb04852.x.
  • Pavlin A, Pompe M, Kočar D. Direct Determination of Kynurenic Acid with HPLC-MS/MS Method in Honey Acta Chimica Slovenica 2023;70(2), doi.org/10.17344/acsi.2023.8079.
  • Schwarcz R, Bruno JP, Muchowski PJ, Wu HQ. Kynurenines in the mammalian brain: when physiology meets pathology Nature Reviews Neuroscience 2012;13(7), 465-477, doi.org/10.1038/nrn3257.
  • Smirnov VB, Chesnokova EG, Lopatina NG, Voike E. Characteristics of neuron activity in the honeybee (Apis mellifera L.) in conditions of kynurenine deficiency Neuroscience and Behavioral Physiology 2006;36, 213-216.
  • Sousa A, Ribeiro C, Gonçalves V M, Barbosa J, Peixoto B, Andrade A, et al. Development and validation of a liquid chromatography method using UV/fluorescence detection for the quantitative determination of metabolites of the kynurenine pathway in human urine: application to patients with heart failure Journal of Pharmaceutical and Biomedical Analysis 2021;198, 113997, doi.org/10.1016/j.jpba.2021.113997.
  • Starratt AN, Caveney S. Quinoline-2-carboxylic acids from Ephedra species. Phytochemistry 1996;42(5), 1477-1478, doi.org/10.1016/0031-9422(96)00126-4.
  • Turski MP, Chwil S, Turska M, Chwil M, Kocki T, Rajtar G, et al. An exceptionally high content of kynurenic acid in chestnut honey and flowers of chestnut tree Journal of Food Composition and Analysis 2016;48, 67-72, doi.org/10.1016/j.jfca.2016.02.003.
  • Turski MP, Turska M, Zgrajka W, Bartnik M, Kocki T, Turski WA. Distribution, synthesis, and absorption of kynurenic acid in plants Planta medica 2011;77(08), 858-864, doi.org/10.1055/s-0030-1250604.
  • Varga G, Érces D, Fazekas B, Fülöp M, Kovács T, Kaszaki J, et al. N‐methyl‐d‐aspartate receptor antagonism decreases motility and inflammatory activation in the early phase of acute experimental colitis in the rat Neurogastroenterology & Motility 2010;22(2), 217-e68, doi.org/10.1111/j.1365-2982.2009.01390.x.
  • Walczak K, Dąbrowski W, Langner E, Zgrajka W, Piłat J, Kocki T, et al. Kynurenic acid synthesis and kynurenine aminotransferases expression in colon derived normal and cancer cells Scandinavian journal of gastroenterology 2011;46(7-8), 903-912, doi.org/10.3109/00365521.2011.579159.
  • Wang J, Simonavicius N, Wu X, Swaminath G, Reagan J, Tian H, et al. Kynurenic acid as a ligand for orphan G protein-coupled receptor GPR35 Journal of biological chemistry 2006;281(31), 22021-22028, doi.org/10.1074/jbc.M603503200.
  • Wirthgen E, Hoeflich A, Rebl A, Günther J. Kynurenic acid: the Janus-faced role of an immunomodulatory tryptophan metabolite and its link to pathological conditions Frontiers in immunology 2018;8, 1957, doi.org/10.3389/fimmu.2017.01957.

METHOD VALIDATION FOR DETERMINATION OF KYNURENIC ACID CONTENT IN NATURAL PRODUCTS BY RP-HPLC-UV

Yıl 2024, Cilt: 24 Sayı: 2, 188 - 196, 18.11.2024
https://doi.org/10.31467/uluaricilik.1468749

Öz

Kynurenic acid (KYNA) is a metabolite with pharmacoactive properties found primarily in chestnut honey, linden, and other honeys. Considering the anti-inflammatory and immunosuppressive functions of KYNA, it can be seen that it has bidirectional effects on biological pathways. For this reason, determining and knowing the amount of honey, an important natural product can have a high impact on health. Studies on the detection of this metabolite in both natural products and animal tissues are ongoing, and it is important to develop fast and easily applicable methods. Within the scope of this study, a new method was created using an ultraviolet detector (RP-HPLC-UV) in reverse-phase high-performance liquid chromatography to determine the KYNA content of natural products (honey, chestnut pollen, and chestnut flowers) quantitatively in a short time. According to the data obtained, LOD and LOQ values were found to be 0.030 µg/mL and 0.092 µg/mL, respectively. At the same time, solutions of KYNA prepared in ultrapure water (UPW), 70% EtOH, EtOH and MeOH solvents were analyzed in this method, and it was found that UPW was the best solvent. The findings of this research can contribute significantly, particularly in the application of measuring KYNA, to distinguishing the botanical origin of chestnut honey.

Kaynakça

  • Adams S, Braidy N, Bessesde A, Brew BJ, Grant R, Teo C, Guillemin GJ. The kynurenine pathway in brain tumor pathogenesis Cancer research 2012; 72(22), 5649-5657, doi.org/10.1158/0008-5472.CAN-12-0549.
  • Alt A, Weiss B, Ogden AM, Knauss JL, Oler J, Ho K, et al. Pharmacological characterization of glutamatergic agonists and antagonists at recombinant human homomeric and heteromeric kainate receptors in vitro Neuropharmacology 2004;46(6), 793-806, doi.org/10.1016/j.neuropharm.2003.11.026.
  • Beretta G, Artali R, Caneva E, Orlandini S, Centini M, Facino RM. Quinoline alkaloids in honey: further analytical (HPLC-DAD-ESI-MS, multidimensional diffusion-ordered NMR spectroscopy), theoretical and chemometric studies Journal of Pharmaceutical and Biomedical Analysis 2009;50(3), 432-439, doi.org/10.1016/j.jpba.2009.05.029.
  • Beretta G, Caneva E, Regazzoni L, Bakhtyari NG, Facino RM. A solid-phase extraction procedure coupled to 1H NMR, with chemometric analysis, to seek reliable markers of the botanical origin of honey Analytica chimica acta 2008;620(1-2), 176-182, doi.org/10.1016/j.aca.2008.05.025.
  • Coşkun ZG, Coşkun F. A Review about Honey Effect on Human Body Journal of Apitherapy and Nature 2022;5(1), 35-68, doi.org/10.35206/jan.963498.
  • Fukushima T, Umino M, Sakamoto T, Onozato M. A review of chromatographic methods for bioactive tryptophan metabolites, kynurenine, kynurenic acid, quinolinic acid, and others, in biological fluids Biomedical Chromatography 2022;36(5), e5308, doi.org/10.1002/bmc.5308.
  • Glavin GB, Pinsky C. Kynurenic acid attenuates experimental ulcer formation and basal gastric acid secretion in rats Research communications in chemical pathology and pharmacology 1989;64(1), 111-119.
  • Hilmas C, Pereira EF, Alkondon M, Rassoulpour A, Schwarcz R, Albuquerque EX. The brain metabolite kynurenic acid inhibits α7 nicotinic receptor activity and increases non-α7 nicotinic receptor expression: physiopathological implications Journal of Neuroscience 2001;21(19), 7463-7473.
  • Kaszaki J, Palásthy Z, Erczes D, Racz A, Torday C, Varga G, et al. Kynurenic acid inhibits intestinal hypermotility and xanthine oxidase activity during experimental colon obstruction in dogs Neurogastroenterology & Motility 2008;20(1), 53-62, doi.org/10.1111/j.1365-2982.2007.00989.x.
  • Kim J, Kim D, Lee S. Quantitative Analysis of Kynurenic Acid in Chestnut Honey from Different Regions and Method Validation Korean Journal of Pharmacognosy 2022;53(2), 111-118.
  • Kuc D, Rahnama M, Tomaszewski T, Rzeski W, Wejksza K, Urbanik-Sypniewska T., et al. Kynurenic acid in human saliva-does it influence oral microflora? Pharmacological Reports 2006;58(3), 393.
  • Kuc D, Zgrajka W, Parada-Turska J, Urbanik-Sypniewska T, Turski WA. Micromolar concentration of kynurenic acid in rat small intestine Amino acids 2008;35, 503-505, doi.org/10.1007/s00726-007-0631-z.
  • Lan-Gan, P., Ai-Guo, T., Xi-ming, M., Xi-bo, L., & Xiang, A. (2009). More rapid and sensitive method for simultaneous determination of tryptophan and kynurenic acid by HPLC. Clinical biochemistry, 42(4-5), 420-425, doi.org/10.1016/j.clinbiochem.2008.11.011.
  • Liebig JV. Über kynurensäure Annalen der Chemie und Pharmacie 1853;86(1), 125-126.
  • Mok MS, Fricker AC, Weil A, Kew JN. Electrophysiological characterisation of the actions of kynurenic acid at ligand-gated ion channels Neuropharmacology 2009;57(3), 242-249, doi.org/10.1016/j.neuropharm.2009.06.003.
  • Moroni F, Russi P, Lombardi G, Beni M, Carla V. Presence of kynurenic acid in the mammalian brain Journal of neurochemistry 1988;51(1), 177-180, doi.org/10.1111/j.1471-4159.1988.tb04852.x.
  • Pavlin A, Pompe M, Kočar D. Direct Determination of Kynurenic Acid with HPLC-MS/MS Method in Honey Acta Chimica Slovenica 2023;70(2), doi.org/10.17344/acsi.2023.8079.
  • Schwarcz R, Bruno JP, Muchowski PJ, Wu HQ. Kynurenines in the mammalian brain: when physiology meets pathology Nature Reviews Neuroscience 2012;13(7), 465-477, doi.org/10.1038/nrn3257.
  • Smirnov VB, Chesnokova EG, Lopatina NG, Voike E. Characteristics of neuron activity in the honeybee (Apis mellifera L.) in conditions of kynurenine deficiency Neuroscience and Behavioral Physiology 2006;36, 213-216.
  • Sousa A, Ribeiro C, Gonçalves V M, Barbosa J, Peixoto B, Andrade A, et al. Development and validation of a liquid chromatography method using UV/fluorescence detection for the quantitative determination of metabolites of the kynurenine pathway in human urine: application to patients with heart failure Journal of Pharmaceutical and Biomedical Analysis 2021;198, 113997, doi.org/10.1016/j.jpba.2021.113997.
  • Starratt AN, Caveney S. Quinoline-2-carboxylic acids from Ephedra species. Phytochemistry 1996;42(5), 1477-1478, doi.org/10.1016/0031-9422(96)00126-4.
  • Turski MP, Chwil S, Turska M, Chwil M, Kocki T, Rajtar G, et al. An exceptionally high content of kynurenic acid in chestnut honey and flowers of chestnut tree Journal of Food Composition and Analysis 2016;48, 67-72, doi.org/10.1016/j.jfca.2016.02.003.
  • Turski MP, Turska M, Zgrajka W, Bartnik M, Kocki T, Turski WA. Distribution, synthesis, and absorption of kynurenic acid in plants Planta medica 2011;77(08), 858-864, doi.org/10.1055/s-0030-1250604.
  • Varga G, Érces D, Fazekas B, Fülöp M, Kovács T, Kaszaki J, et al. N‐methyl‐d‐aspartate receptor antagonism decreases motility and inflammatory activation in the early phase of acute experimental colitis in the rat Neurogastroenterology & Motility 2010;22(2), 217-e68, doi.org/10.1111/j.1365-2982.2009.01390.x.
  • Walczak K, Dąbrowski W, Langner E, Zgrajka W, Piłat J, Kocki T, et al. Kynurenic acid synthesis and kynurenine aminotransferases expression in colon derived normal and cancer cells Scandinavian journal of gastroenterology 2011;46(7-8), 903-912, doi.org/10.3109/00365521.2011.579159.
  • Wang J, Simonavicius N, Wu X, Swaminath G, Reagan J, Tian H, et al. Kynurenic acid as a ligand for orphan G protein-coupled receptor GPR35 Journal of biological chemistry 2006;281(31), 22021-22028, doi.org/10.1074/jbc.M603503200.
  • Wirthgen E, Hoeflich A, Rebl A, Günther J. Kynurenic acid: the Janus-faced role of an immunomodulatory tryptophan metabolite and its link to pathological conditions Frontiers in immunology 2018;8, 1957, doi.org/10.3389/fimmu.2017.01957.
Toplam 27 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Geleneksel, Tamamlayıcı ve Bütünleştirici Tıp (Diğer)
Bölüm Araştırma Makaleleri
Yazarlar

Yakup Kara 0000-0003-3121-5023

Sevgi Kolaylı 0000-0003-0437-6139

Erken Görünüm Tarihi 12 Kasım 2024
Yayımlanma Tarihi 18 Kasım 2024
Gönderilme Tarihi 15 Nisan 2024
Kabul Tarihi 17 Mayıs 2024
Yayımlandığı Sayı Yıl 2024 Cilt: 24 Sayı: 2

Kaynak Göster

Vancouver Kara Y, Kolaylı S. METHOD VALIDATION FOR DETERMINATION OF KYNURENIC ACID CONTENT IN NATURAL PRODUCTS BY RP-HPLC-UV. U.Arı D.-U.Bee J. 2024;24(2):188-96.

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