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DERİN ÖTEKTİK ÇÖZÜCÜNÜN Rheum ribes KÖKLERİNDEN FENOLİK BİLEŞİK EKSTRAKSİYONU ÜZERİNE ETKİSİ

Yıl 2023, , 199 - 208, 15.02.2023
https://doi.org/10.15237/gida.GD22107

Öz

Bu çalışmada ışkın bitkisi (Rheum ribes) köklerinden biyoaktif bileşik eldesinde farklı çözücü tipleri değerlendirilmiştir. Yeşil çözücü olarak kolin klorür ve laktik asit ile hazırlanan farklı molar oranda (1:1, 1:2, 1:3) derin ötektik çözücüler ve su kullanılmıştır. Toplam fenolik bileşik miktarı derin ötektik çözücü ile etanol ekstraktına benzer olarak yüksek bulunmuştur. Toplam flavonoid bileşik ekstraksiyonunda en yüksek değer etanol ile elde edilirken ikinci sırada derin ötektik çözücü gelmektedir. Antioksidan aktivite üzerine ise en etkili çözücünün derin ötektik çözücü (1:3) olduğu saptanmıştır. Ek olarak temel bileşen analizi ile farklı çözücüler kullanılarak hazırlanan ışkın ekstraktlarının biyoaktif içerik (toplam fenolik, toplam flavonoid bileşik, antioksidan aktivite) açısından benzerlik/farklılıkları değerlendirilmiştir. Sonuç olarak, ışkından biyoaktif bileşik ekstraksiyonunda organik çözücülere alternatif olarak derin ötektik çözücünün kullanımı uygun bulunmuştur.

Destekleyen Kurum

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Proje Numarası

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Teşekkür

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Kaynakça

  • Abbott, A.P., Capper, G., Davies, D.L., Rasheed, R.K., Tambyrajah, V. (2003). Novel solvent properties of choline chloride/urea mixtures. Chemical Communications, 1:70-71.
  • Akkuş, Y. (2018). Rheum ribes (Işkın Otu)’in Metanol Ekstresinin Düzenli Aerobik Yüzme Egzersizi Uygulanan Rat Dokularında Antioksidan ve Histopatolojik Etkileri. Doktora tezi, Atatürk Üniversitesi, Kış Sporları ve Spor Bilimleri Enstitüsü, Erzurum, Türkiye s. 84.
  • Alaadin, A.M., Al-Khateeb, E.H., Jäger, A.K. (2007). Antibacterial activity of the Iraqi Rheum ribes root. Pharmaceutical Biology, 45(9):688-690.
  • Apak, R., Güçlü, K., Özyürek, M., Karademir, S.E. (2004). Novel total antioxidant capacity index for dietary polyphenols and vitamins C and E, using their cupric ion reducing capability in the presence of neocuproine: CUPRAC method. Journal of Agricultural and Food Chemistry, 52(26):7970-7981.
  • Apuhan, A.K., Beyazkaya, T. (2019). Bingöl’ün yenilebilir yabani bitkilerinin gastronomi turizmine etkisi üzerine bir araştırma. Tourism and Recreation, 1(1):31-37. Bajkacz, S., Adamek, J. (2018). Development of a method based on natural deep eutectic solvents for extraction of flavonoids from food samples. Food Analytical Methods, 11(5):1330-1344.
  • Bao, J.S., Cai, Y.Z., Sun, M., Wang, G., Corke, H. (2005). Anthocyanins, flavonols, and free radical scavenging activity of chinese bayberry (Myrica rubra) extracts and their color properties and stability. Journal of Agricultural and Food Chemistry, 53:2327–2332.
  • Bayram, S., Kutlu, N., Gerçek, Y.C., Çelik, S., Bayram, N.E. (2022). Bioactive compounds of deep eutectic solvents extracts of Hypericum perforatum L.: Polyphenolic-organic acid profile by LC-MS/MS and pharmaceutical activity. Food Bioscience, 49:101926.
  • Benzie, I.F., Strain, J.J. (1996). The ferric reducing ability of plasma (FRAP) as a measure of "antioxidant power": the FRAP assay. Anal Biochem., 239(1):70-76.
  • Bubalo, M. C., Ćurko, N., Tomašević, M., Ganić, K.K., Redovniković, I.R. (2016). Green extraction of grape skin phenolics by using deep eutectic solvents. Food Chemistry, 200:159-166.
  • Chandra, S., Khan, S., Avula, B., Lata, H., Yang, M.H., ElSohly, M.A., Khan, I.A. (2014). Assessment of total phenolic and flavonoid content, antioxidant properties, and yield of aeroponically and conventionally grown leafy vegetables and fruit crops: a comparative study. Evidence-Based Complementary and Alternative Medicine, 2014:253875.
  • Chemat, F., Vian, M.A., Fabiano-Tixier, A.S., Nutrizio, M., Jambrak, A.R., Munekata, P.E., Lorenzo, J.M., Barba, F.J., Binello, A., Cravotto, G. (2020). A review of sustainable and intensified techniques for extraction of food and natural products. Green Chemistry, 22(8):2325-2353.
  • Cui, Y., Li, C., Yin, J., Li, S., Jia, Y., Bao, M. (2017). Design, synthesis and properties of acidic deep eutectic solvents based on choline chloride. Journal of Molecular Liquids, 236:338-343. Farzami Sepehr, M., Ghorbanli, M. (2002). Effects of nutritional factors on the formation of Anthraquinones in callus cultures of Rheum ribes. Plant Cell Tissue and Organ Culture, 68(2):171-175.
  • Garcia-Salas, P., Morales-Soto, A., Segura-Carretero, A., Fernández-Gutiérrez, A. (2010). Phenolic-compound-extraction systems for fruit and vegetable samples. Molecules, 15(12):8813-8826.
  • Inaltong, T. (2015). Türkiye’nin otları Erişim adresi: http://www.turkishcuisine.org /ingredients-7/ingredients-used-inturkishcuisine-66/wild-greens-and-herbs-188.html.
  • Karoui, R., Downey, G., Blecker, C. (2010). Mid-infrared spectroscopy coupled with chemometrics: a tool for the analysis of intact food systems and the exploration of their molecular structure− quality relationships− a review. Chemical Reviews, 110(10):6144-6168.
  • Keser, S., Keser, F., Karatepe, M., Kaygili, O., Tekin, S., Turkoglu, I., Demir, E., Yilmaz, O., Kirbag, S., Sandal, S. (2020). Bioactive contents, in vitro antiradical, antimicrobial and cytotoxic properties of rhubarb (Rheum ribes L.) extracts. Natural Product Research, 34(23):3353-3357.
  • Li, J., Han, Z., Zou, Y., Yu, B. (2015). Efficient extraction of major catechins in Camellia sinensis leaves using green choline chloride-based deep eutectic solvents. RSC Advances, 5(114):93937-93944.
  • McDonald, S., Prenzler, P.D., Antolovich, M., Robards, K. (2001). Phenolic content and antioxidant activity of olive extracts. Food Chemistry, 73(1):73-84.
  • Munzuroğlu, Ö., Karataş, F., Gür, N. (2000). A study of the levels of vitamins A, E and C and selenium in rhubarb (Rheum ribes L.). Turkish Journal of Biology, 24(3):397-404.
  • Panzella, L., Moccia, F., Nasti, R., Marzorati, S., Verotta, L., Napolitano, A. (2020). Bioactive phenolic compounds from agri-food wastes: An update on green and sustainable extraction methodologies. Frontiers in Nutrition, 7:60.
  • Radošević, K., Bubalo, M.C., Srček, V.G., Grgas, D., Dragičević, T.L., Redovniković, I.R. (2015). Evaluation of toxicity and biodegradability of choline chloride based deep eutectic solvents. Ecotoxicology and Environmental Safety, 112:46-53.
  • Reina, L.J.C., López, G.D., Durán-Aranguren, D.D., Quiroga, I., Carazzone, C., Sierra, R. (2023). Compressed fluids and Soxhlet extraction for the valorization of compounds from Colombian cashew (Anacardium occidentale) nut shells aimed at a cosmetic application. The Journal of Supercritical Fluids, 192:105808.
  • Ruesgas-Ramón, M., Figueroa-Espinoza, M.C., Durand, E. (2017). Application of deep eutectic solvents (DES) for phenolic compounds extraction: Overview, challenges, and opportunities. Journal of Agricultural and Food Chemistry, 65(18):3591-3601.
  • Stalikas, C.D. (2007). Extraction, separation, and detection methods for phenolic acids and flavonoids. Journal of Separation Science, 30(18):3268-3295.
  • Tang, B., Zhang, H., Row, K.H. (2015). Application of deep eutectic solvents in the extraction and separation of target compounds from various samples. Journal of Separation Science, 38(6):1053-1064.
  • Welton, T. (2015). Solvents and sustainable chemistry. Proceedings of the Royal Society A: Mathematical, Physical and Engineering Sciences, 471(2183):20150502.
  • Wojeicchowski, J.P., Marques, C., Igarashi-Mafra, L., Coutinho, J.A., Mafra, M.R. (2021). Extraction of phenolic compounds from rosemary using choline chloride–based deep eutectic solvents. Separation and Purification Technology, 258:117975.
  • Wu, L., Li, L., Chen, S., Wang, L., Lin, X. (2020). Deep eutectic solvent-based ultrasonic-assisted extraction of phenolic compounds from Moringa oleifera L. leaves: Optimization, comparison and antioxidant activity. Separation and Purification Technology, 247:117014.
  • Xu, G.C., Ding, J.C., Han, R.Z., Dong, J.J., Ni, Y. (2016). Enhancing cellulose accessibility of corn stover by deep eutectic solvent pretreatment for butanol fermentation. Bioresource Technology, 203:364-369. https://doi.org/10.1016/j.biortech.2015.11.002.
  • Yu, Q., Wang, F., Jian, Y., Chernyshev, V.M., Zhang, Y., Wang, Z., Yuan, Z., Chen, X. (2022). Extraction of flavonoids from Glycyrrhiza residues using deep eutectic solvents and its molecular mechanism. Journal of Molecular Liquids, 363:119848.
  • Zainal-Abidin, M.H., Hayyan, M., Hayyan, A., Jayakumar, N.S. (2017). New horizons in the extraction of bioactive compounds using deep eutectic solvents: A review. Analytica Chimica Acta, 979:1-23.
  • Zannou, O., Koca, I. (2020). Optimization and stabilization of the antioxidant properties from Alkanet (Alkanna tinctoria) with natural deep eutectic solvents. Arabian Journal of Chemistry, 13(8):6437-6450.
  • Zhao, B.Y., Xu, P., Yang, F.X., Wu, H., Zong, M.H., Lou, W.Y. (2015). Biocompatible deep eutectic solvents based on choline chloride: characterization and application to the extraction of rutin from Sophora japonica. ACS Sustainable Chemistry & Engineering, 3(11):2746-2755.
  • Zhou, S., Fang, Z., Lü, Y., Chen, J., Liu, D., Ye, X. (2009). Phenolics and antioxidant properties of bayberry (Myrica rubra Sieb. et Zucc.) pomace. Food Chemistry, 112:394-399.

IMPACT OF DEEP EUTECTIC SOLVENT ON PHENOLIC COMPOUND EXTRACTION FROM Rheum ribes ROOTS

Yıl 2023, , 199 - 208, 15.02.2023
https://doi.org/10.15237/gida.GD22107

Öz

In this study, different solvent types were evaluated in obtaining bioactive compounds from rhubarb (Rheum ribes) roots. Deep eutectic solvents prepared with choline chloride and lactic acid in different molar ratios (1:1, 1:2, 1:3) and water were used, as green solvents The total phenolic compounds were found to be high with deep eutectic solvent similar to the ethanol extract. The highest value is obtained with ethanol for total flavonoid compound extraction, while deep eutectic solvent comes second. For the antioxidant activity, it was determined that the most effective solvent was the deep eutectic solvent (1:3). In addition, the similarities/differences in terms of bioactive compounds (total phenolic, total flavonoid compound, antioxidant activity) of rhubarb extracts prepared using different solvents were evaluated with principal component analysis. As a result, the use of deep eutectic solvent was found to be appropriate as an alternative to organic solvents in bioactive compound extraction from rhubarb.

Proje Numarası

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Kaynakça

  • Abbott, A.P., Capper, G., Davies, D.L., Rasheed, R.K., Tambyrajah, V. (2003). Novel solvent properties of choline chloride/urea mixtures. Chemical Communications, 1:70-71.
  • Akkuş, Y. (2018). Rheum ribes (Işkın Otu)’in Metanol Ekstresinin Düzenli Aerobik Yüzme Egzersizi Uygulanan Rat Dokularında Antioksidan ve Histopatolojik Etkileri. Doktora tezi, Atatürk Üniversitesi, Kış Sporları ve Spor Bilimleri Enstitüsü, Erzurum, Türkiye s. 84.
  • Alaadin, A.M., Al-Khateeb, E.H., Jäger, A.K. (2007). Antibacterial activity of the Iraqi Rheum ribes root. Pharmaceutical Biology, 45(9):688-690.
  • Apak, R., Güçlü, K., Özyürek, M., Karademir, S.E. (2004). Novel total antioxidant capacity index for dietary polyphenols and vitamins C and E, using their cupric ion reducing capability in the presence of neocuproine: CUPRAC method. Journal of Agricultural and Food Chemistry, 52(26):7970-7981.
  • Apuhan, A.K., Beyazkaya, T. (2019). Bingöl’ün yenilebilir yabani bitkilerinin gastronomi turizmine etkisi üzerine bir araştırma. Tourism and Recreation, 1(1):31-37. Bajkacz, S., Adamek, J. (2018). Development of a method based on natural deep eutectic solvents for extraction of flavonoids from food samples. Food Analytical Methods, 11(5):1330-1344.
  • Bao, J.S., Cai, Y.Z., Sun, M., Wang, G., Corke, H. (2005). Anthocyanins, flavonols, and free radical scavenging activity of chinese bayberry (Myrica rubra) extracts and their color properties and stability. Journal of Agricultural and Food Chemistry, 53:2327–2332.
  • Bayram, S., Kutlu, N., Gerçek, Y.C., Çelik, S., Bayram, N.E. (2022). Bioactive compounds of deep eutectic solvents extracts of Hypericum perforatum L.: Polyphenolic-organic acid profile by LC-MS/MS and pharmaceutical activity. Food Bioscience, 49:101926.
  • Benzie, I.F., Strain, J.J. (1996). The ferric reducing ability of plasma (FRAP) as a measure of "antioxidant power": the FRAP assay. Anal Biochem., 239(1):70-76.
  • Bubalo, M. C., Ćurko, N., Tomašević, M., Ganić, K.K., Redovniković, I.R. (2016). Green extraction of grape skin phenolics by using deep eutectic solvents. Food Chemistry, 200:159-166.
  • Chandra, S., Khan, S., Avula, B., Lata, H., Yang, M.H., ElSohly, M.A., Khan, I.A. (2014). Assessment of total phenolic and flavonoid content, antioxidant properties, and yield of aeroponically and conventionally grown leafy vegetables and fruit crops: a comparative study. Evidence-Based Complementary and Alternative Medicine, 2014:253875.
  • Chemat, F., Vian, M.A., Fabiano-Tixier, A.S., Nutrizio, M., Jambrak, A.R., Munekata, P.E., Lorenzo, J.M., Barba, F.J., Binello, A., Cravotto, G. (2020). A review of sustainable and intensified techniques for extraction of food and natural products. Green Chemistry, 22(8):2325-2353.
  • Cui, Y., Li, C., Yin, J., Li, S., Jia, Y., Bao, M. (2017). Design, synthesis and properties of acidic deep eutectic solvents based on choline chloride. Journal of Molecular Liquids, 236:338-343. Farzami Sepehr, M., Ghorbanli, M. (2002). Effects of nutritional factors on the formation of Anthraquinones in callus cultures of Rheum ribes. Plant Cell Tissue and Organ Culture, 68(2):171-175.
  • Garcia-Salas, P., Morales-Soto, A., Segura-Carretero, A., Fernández-Gutiérrez, A. (2010). Phenolic-compound-extraction systems for fruit and vegetable samples. Molecules, 15(12):8813-8826.
  • Inaltong, T. (2015). Türkiye’nin otları Erişim adresi: http://www.turkishcuisine.org /ingredients-7/ingredients-used-inturkishcuisine-66/wild-greens-and-herbs-188.html.
  • Karoui, R., Downey, G., Blecker, C. (2010). Mid-infrared spectroscopy coupled with chemometrics: a tool for the analysis of intact food systems and the exploration of their molecular structure− quality relationships− a review. Chemical Reviews, 110(10):6144-6168.
  • Keser, S., Keser, F., Karatepe, M., Kaygili, O., Tekin, S., Turkoglu, I., Demir, E., Yilmaz, O., Kirbag, S., Sandal, S. (2020). Bioactive contents, in vitro antiradical, antimicrobial and cytotoxic properties of rhubarb (Rheum ribes L.) extracts. Natural Product Research, 34(23):3353-3357.
  • Li, J., Han, Z., Zou, Y., Yu, B. (2015). Efficient extraction of major catechins in Camellia sinensis leaves using green choline chloride-based deep eutectic solvents. RSC Advances, 5(114):93937-93944.
  • McDonald, S., Prenzler, P.D., Antolovich, M., Robards, K. (2001). Phenolic content and antioxidant activity of olive extracts. Food Chemistry, 73(1):73-84.
  • Munzuroğlu, Ö., Karataş, F., Gür, N. (2000). A study of the levels of vitamins A, E and C and selenium in rhubarb (Rheum ribes L.). Turkish Journal of Biology, 24(3):397-404.
  • Panzella, L., Moccia, F., Nasti, R., Marzorati, S., Verotta, L., Napolitano, A. (2020). Bioactive phenolic compounds from agri-food wastes: An update on green and sustainable extraction methodologies. Frontiers in Nutrition, 7:60.
  • Radošević, K., Bubalo, M.C., Srček, V.G., Grgas, D., Dragičević, T.L., Redovniković, I.R. (2015). Evaluation of toxicity and biodegradability of choline chloride based deep eutectic solvents. Ecotoxicology and Environmental Safety, 112:46-53.
  • Reina, L.J.C., López, G.D., Durán-Aranguren, D.D., Quiroga, I., Carazzone, C., Sierra, R. (2023). Compressed fluids and Soxhlet extraction for the valorization of compounds from Colombian cashew (Anacardium occidentale) nut shells aimed at a cosmetic application. The Journal of Supercritical Fluids, 192:105808.
  • Ruesgas-Ramón, M., Figueroa-Espinoza, M.C., Durand, E. (2017). Application of deep eutectic solvents (DES) for phenolic compounds extraction: Overview, challenges, and opportunities. Journal of Agricultural and Food Chemistry, 65(18):3591-3601.
  • Stalikas, C.D. (2007). Extraction, separation, and detection methods for phenolic acids and flavonoids. Journal of Separation Science, 30(18):3268-3295.
  • Tang, B., Zhang, H., Row, K.H. (2015). Application of deep eutectic solvents in the extraction and separation of target compounds from various samples. Journal of Separation Science, 38(6):1053-1064.
  • Welton, T. (2015). Solvents and sustainable chemistry. Proceedings of the Royal Society A: Mathematical, Physical and Engineering Sciences, 471(2183):20150502.
  • Wojeicchowski, J.P., Marques, C., Igarashi-Mafra, L., Coutinho, J.A., Mafra, M.R. (2021). Extraction of phenolic compounds from rosemary using choline chloride–based deep eutectic solvents. Separation and Purification Technology, 258:117975.
  • Wu, L., Li, L., Chen, S., Wang, L., Lin, X. (2020). Deep eutectic solvent-based ultrasonic-assisted extraction of phenolic compounds from Moringa oleifera L. leaves: Optimization, comparison and antioxidant activity. Separation and Purification Technology, 247:117014.
  • Xu, G.C., Ding, J.C., Han, R.Z., Dong, J.J., Ni, Y. (2016). Enhancing cellulose accessibility of corn stover by deep eutectic solvent pretreatment for butanol fermentation. Bioresource Technology, 203:364-369. https://doi.org/10.1016/j.biortech.2015.11.002.
  • Yu, Q., Wang, F., Jian, Y., Chernyshev, V.M., Zhang, Y., Wang, Z., Yuan, Z., Chen, X. (2022). Extraction of flavonoids from Glycyrrhiza residues using deep eutectic solvents and its molecular mechanism. Journal of Molecular Liquids, 363:119848.
  • Zainal-Abidin, M.H., Hayyan, M., Hayyan, A., Jayakumar, N.S. (2017). New horizons in the extraction of bioactive compounds using deep eutectic solvents: A review. Analytica Chimica Acta, 979:1-23.
  • Zannou, O., Koca, I. (2020). Optimization and stabilization of the antioxidant properties from Alkanet (Alkanna tinctoria) with natural deep eutectic solvents. Arabian Journal of Chemistry, 13(8):6437-6450.
  • Zhao, B.Y., Xu, P., Yang, F.X., Wu, H., Zong, M.H., Lou, W.Y. (2015). Biocompatible deep eutectic solvents based on choline chloride: characterization and application to the extraction of rutin from Sophora japonica. ACS Sustainable Chemistry & Engineering, 3(11):2746-2755.
  • Zhou, S., Fang, Z., Lü, Y., Chen, J., Liu, D., Ye, X. (2009). Phenolics and antioxidant properties of bayberry (Myrica rubra Sieb. et Zucc.) pomace. Food Chemistry, 112:394-399.
Toplam 34 adet kaynakça vardır.

Ayrıntılar

Birincil Dil Türkçe
Konular Gıda Mühendisliği
Bölüm Makaleler
Yazarlar

Naciye Kutlu Kantar 0000-0002-4075-8823

Proje Numarası -
Yayımlanma Tarihi 15 Şubat 2023
Yayımlandığı Sayı Yıl 2023

Kaynak Göster

APA Kutlu Kantar, N. (2023). DERİN ÖTEKTİK ÇÖZÜCÜNÜN Rheum ribes KÖKLERİNDEN FENOLİK BİLEŞİK EKSTRAKSİYONU ÜZERİNE ETKİSİ. Gıda, 48(1), 199-208. https://doi.org/10.15237/gida.GD22107
AMA Kutlu Kantar N. DERİN ÖTEKTİK ÇÖZÜCÜNÜN Rheum ribes KÖKLERİNDEN FENOLİK BİLEŞİK EKSTRAKSİYONU ÜZERİNE ETKİSİ. GIDA. Şubat 2023;48(1):199-208. doi:10.15237/gida.GD22107
Chicago Kutlu Kantar, Naciye. “DERİN ÖTEKTİK ÇÖZÜCÜNÜN Rheum Ribes KÖKLERİNDEN FENOLİK BİLEŞİK EKSTRAKSİYONU ÜZERİNE ETKİSİ”. Gıda 48, sy. 1 (Şubat 2023): 199-208. https://doi.org/10.15237/gida.GD22107.
EndNote Kutlu Kantar N (01 Şubat 2023) DERİN ÖTEKTİK ÇÖZÜCÜNÜN Rheum ribes KÖKLERİNDEN FENOLİK BİLEŞİK EKSTRAKSİYONU ÜZERİNE ETKİSİ. Gıda 48 1 199–208.
IEEE N. Kutlu Kantar, “DERİN ÖTEKTİK ÇÖZÜCÜNÜN Rheum ribes KÖKLERİNDEN FENOLİK BİLEŞİK EKSTRAKSİYONU ÜZERİNE ETKİSİ”, GIDA, c. 48, sy. 1, ss. 199–208, 2023, doi: 10.15237/gida.GD22107.
ISNAD Kutlu Kantar, Naciye. “DERİN ÖTEKTİK ÇÖZÜCÜNÜN Rheum Ribes KÖKLERİNDEN FENOLİK BİLEŞİK EKSTRAKSİYONU ÜZERİNE ETKİSİ”. Gıda 48/1 (Şubat 2023), 199-208. https://doi.org/10.15237/gida.GD22107.
JAMA Kutlu Kantar N. DERİN ÖTEKTİK ÇÖZÜCÜNÜN Rheum ribes KÖKLERİNDEN FENOLİK BİLEŞİK EKSTRAKSİYONU ÜZERİNE ETKİSİ. GIDA. 2023;48:199–208.
MLA Kutlu Kantar, Naciye. “DERİN ÖTEKTİK ÇÖZÜCÜNÜN Rheum Ribes KÖKLERİNDEN FENOLİK BİLEŞİK EKSTRAKSİYONU ÜZERİNE ETKİSİ”. Gıda, c. 48, sy. 1, 2023, ss. 199-08, doi:10.15237/gida.GD22107.
Vancouver Kutlu Kantar N. DERİN ÖTEKTİK ÇÖZÜCÜNÜN Rheum ribes KÖKLERİNDEN FENOLİK BİLEŞİK EKSTRAKSİYONU ÜZERİNE ETKİSİ. GIDA. 2023;48(1):199-208.

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