Investigation of the inhibition effect of pitaya (hylocereus guatemalensis) bark extracts on some metabolic enzymes

Year 2023, Volume: 13 Issue: 3, 595 - 604, 15.07.2023

Rüya Sağlamtaş

https://doi.org/10.17714/gumusfenbil.1256518

Cited By: 1

Abstract

Pitaya is a tropical and subtropical plant with various uses. In this study, the maceration method obtained acetone, ethanol, ethyl acetate, dichloromethane, and methanol from the bark parts of pitaya fruit. The in vitro effects of fruit peel extracts on the critical metabolic enzyme activities of acetylcholinesterase (AChE), butyrylcholinesterase (BChE), human carbonic anhydrase (hCA I and hCA II), and α-glycosidase, were investigated. Pitaya bark ethanol (PBE) (IC50: 20.16±0.22 µg/mL, r2:0.9694) for AChE and Pitaya bark acetone (PBA) (IC50:42.10±1.045 µg/mL, r2:0.9807) extract for BChE showed the most potent inhibition effect. Pitaya bark ethyl acetate (PBEA) extract showed the most potent inhibitory effect for hCA I and hCA II (IC50:53.51±2.22 µg/mL, r2:0.9562 and IC50:26.29±0.34 µg/mL, r2:0.9966), respectively. In addition, PBEA showed the most potent inhibition effect on α-glycosidase enzyme (IC50: 24.54±1.80 µg/mL, r2:0.9199). According to the results, the extracts can be effectively used treatment of diseases such as glaucoma, epilepsy, type 2 Diabetes mellitus (T2DM), and Alzheimer's disease (AD).

Keywords

Enzyme, Enzyme Inhibition, Pitaya

Pitaya (hylocereus guatemalensis) kabuğu ekstraktlarının bazı metabolik enzimler üzerine olan inhibisyon etkisinin araştırılması

Abstract

Pitaya, çeşitli kullanımları olan tropikal ve subtropikal bir bitkidir. Çalışmada maserasyon yöntemi ile pitaya meyvesinin kabuk kısımlarından aseton, etanol, etil asetat, diklorometan ve metanol ekstraktları elde edilmiştir. Meyve kabuğu ekstraktlarının kritik metabolik enzimler olan asetilkolinesteraz (AChE), butirilkolinesteraz (BChE), insan karbonik anhidraz CA I- II ve α-glikozidaz enzim aktiviteleri üzerine in vitro etkileri araştırıldı. AChE için Pitaya kabuğu etanol (PBE) (IC50: 20.16±0.22 µg/mL, r2:0.9694) ve BChE için Pitaya kabuğu aseton (PBA) (IC50:42.10±1.045 µg/mL, r2:0.9807) ekstraktı en güçlü inhibisyon etkisini gösterdi. Pitaya kabuğu etil asetat (PBEA) ekstresi hCA-I ve II için en kuvvetli inhibitör etkiyi gösterdi (sırasıyla IC50:53.51±2.22, r2:0.9562 µg/mL, IC50:26.29±0.34 µg/mL, r2:0.9966). Ek olarak PBEA, a-Glikozidaz enzimi üzerinde en güçlü inhibisyon etkisini göstermiştir (IC50:24.54±1.80 µg/mL, r2:0.9199). Sonuçlara göre ekstraktlar glokom, epilepsi tip 2 Diabetes mellitus (T2DM) ve Alzheimer hastalığı (AH) gibi hastalıkların tedavisinde etkin bir şekilde kullanılabilir.

Keywords

Enzim, Enzim İnhibisyonu, Pitaya

References

• Akıncıoğlu, A., Göksu, S., Naderi, A., Akıncıoğlu, H., Kılınç, N., & Gülçin, İ. (2021). Cholinesterases, carbonic anhydrase inhibitory properties and in silico studies of novel substituted benzylamines derived from dihydrochalcones. Computational Biology and Chemistry, 94, e107565. https://doi.org/10.1016/j.compbiolchem.2021.107565
• Aksu, K., Akıncıoğlu, H., Akıncıoğlu, A., Göksu, S., Tümer, F., & Gülçin, İ. (2018). Synthesis of novel sulfamides incorporating phenethylamines and determination of their inhibition profiles against some metabolic enzymes. Archiv Der Pharmazie, 351(9), e1800150. https://doi.org/10.1002/ardp.201800150
• Al-Mekhlafi, N. A., Mediani, A., Ismail, N. H., Abas, F., Dymerski, T., Lubinska-Szczygeł, M., Vearasilp, S., & Gorinstein, S. (2021). Metabolomic and antioxidant properties of different varieties and origins of dragon fruit. Microchemical Journal, 160, e105687. https://doi.org/10.1016/j.microc.2020.105687
• Anil, D. A., Aydin, B. O., Demir, Y., & Turkmenoglu, B. (2022). Design, synthesis, biological evaluation and molecular docking studies of novel 1H-1,2,3-triazole derivatives as potent inhibitors of carbonic anhydrase, acetylcholinesterase and aldose reductase. Journal of Molecular Structure, 1257, e132613. https://doi.org/10.1016/j.molstruc.2022.132613
• Atmaca, U., Yıldırım, A., Taslimi, P., Çelik, S. T., Gülçin, İ., Supuran, C. T., & Çelik, M. (2018). Intermolecular amination of allylic and benzylic alcohols leads to effective inhibitions of acetylcholinesterase enzyme and carbonic anhydrase I and II isoenzymes. Journal of Biochemical and Molecular Toxicology, 32(8), e22173. https://doi.org/10.1002/jbt.22173
• Biçer, A., Kaya, R., Anıl, B., Turgut Cin, G., Gülcin, İ., & Gültekin, M. S. (2019). Synthesis of novel bis‐sulfone derivatives and their inhibition properties on some metabolic enzymes including carbonic anhydrase, acetylcholinesterase, and butyrylcholinesterase. Journal of Biochemical and Molecular Toxicology, 33(11), e22401. https://doi.org/10.1002/jbt.22401
• Biçer, A., Kaya, R., Yakalı, G., Gültekin, M. S., Cin, G. T., & Gülçin, İ. (2020). Synthesis of novel β-amino carbonyl derivatives and their inhibition effects on some metabolic enzymes. Journal of Molecular Structure, 1204, e127453. https://doi.org/10.1016/j.molstruc.2019.127453
• Burmaoglu, S., Kazancioglu, E. A., Kazancioglu, M. Z., Sağlamtaş, R., Yalcin, G., Gulcin, I., & Algul, O. (2022). Synthesis, molecular docking and some metabolic enzyme inhibition properties of biphenyl-substituted chalcone derivatives. Journal of Molecular Structure, 1254, e132358. https://doi.org/10.1016/j.molstruc.2022.132358
• Burmaoglu, S., Yilmaz, A. O., Polat, M. F., Kaya, R., Gulcin, İ., & Algul, O. (2021). Synthesis of novel tris-chalcones and determination of their inhibition profiles against some metabolic enzymes. Archives of Physiology and Biochemistry, 127(2), 153–161. https://doi.org/10.1080/13813455.2019.1623265
• Castro-Enríquez, D. D., Montaño-Leyva, B., del Toro-Sánchez, C. L., Juárez-Onofre, J. E., Carvajal-Millán, E., López-Ahumada, G. A., Barreras-Urbina, C. G., Tapia-Hernández, J. A., & Rodríguez-Félix, F. (2020). Effect of ultrafiltration of pitaya extract (Stenocereus thurberi) on ıts phytochemical content, antioxidant capacity, and UPLC-DAD-MS profile. Molecules, 25(2), e281. https://doi.org/10.3390/molecules25020281
• Chanda, J., Mukherjee, P. K., Biswas, R., Biswas, S., Tiwari, A. K., & Pargaonkar, A. (2019). UPLC-QTOF-MS analysis of a carbonic anhydrase-inhibiting extract and fractions of luffa acutangula (L.) roxb (ridge gourd). Phytochemical Analysis, 30(2), 148-155. https://doi.org/10.1002/pca.2800
• Chen, Z., Zhong, B., Barrow, C. J., Dunshea, F. R., & Suleria, H. A. R. (2021). Identification of phenolic compounds in Australian grown dragon fruits by LC-ESI-QTOF-MS/MS and determination of their antioxidant potential. Arabian Journal of Chemistry, 14(6), e103151. https://doi.org/10.1016/j.arabjc.2021.103151
• Choo, W. S., & Yong, W. K. (2011). Antioxidant properties of two species of hylocereus fruits. Advances in Applied Science Research, 2(3), 418-425. https://www.semanticscholar.org/paper/Antioxidant-properties-of-two-species-of-Hylocereus-Choo-Yong/2dc82ad38fdddde0ca55d8799be4facb5bf07991
• D’Ambrosio, K., Carradori, S., Cesa, S., Angeli, A., Monti, S. M., Supuran, C. T., & de Simone, G. (2020). Catechols: a new class of carbonic anhydrase inhibitors. Chemical Communications, 56(85), 13033–13036. https://doi.org/10.1039/D0CC05172A Demir, Y., Taslimi, P., Ozaslan, M. S., Oztaskin, N., Çetinkaya, Y., Gulçin, İ., Beydemir, Ş., & Goksu, S. (2018). Antidiabetic potential: ın vitro inhibition effects of bromophenol and diarylmethanones derivatives on metabolic enzymes. Archiv Der Pharmazie, 351(12), e1800263. https://doi.org/10.1002/ardp.201800263
• Demir, Y., Durmaz, L., Taslimi, P., & Gulçin, İ. (2019). Antidiabetic properties of dietary phenolic compounds: ınhibition effects on α-amylase, aldose reductase, and α-glycosidase. Biotechnology and Applied Biochemistry, 66(5), 781-786. https://doi.org/10.1002/bab.1781
• Demir, Y., Duran, H. E., Durmaz, L., Taslimi, P., Beydemir, Ş., & Gulçin, İ. (2020). The ınfluence of some nonsteroidal anti-inflammatory drugs on metabolic enzymes of aldose reductase, sorbitol dehydrogenase, and α-glycosidase: a perspective for metabolic disorders. Applied Biochemistry and Biotechnology, 190(2), 437-447. https://doi.org/10.1007/s12010-019-03099-7
• Ellman, G. L., Courtney, K. D., Andres, V., & Featherstone, R. M. (1961). A new and rapid colorimetric determination of acetylcholinesterase activity. Biochemical Pharmacology, 7(2), 91-95. https://doi.org/10.1016/0006-2952(61)90145-9
• Erukainure, O. L., Sanni, O., Ijomone, O. M., Ibeji, C. U., Chukwuma, C. I., & Islam, M. S. (2019). The antidiabetic properties of the hot water extract of kola nut (cola nitida (vent.) schott & endl.) in type 2 diabetic rats. Journal of Ethnopharmacology, 242, e112033. https://doi.org/10.1016/j.jep.2019.112033
• García-Cruz, L., Dueñas, M., Santos-Buelgas, C., Valle-Guadarrama, S., & Salinas-Moreno, Y. (2017). Betalains and phenolic compounds profiling and antioxidant capacity of pitaya (stenocereus spp.) fruit from two species (S. Pruinosus and S. stellatus). Food Chemistry, 234, 111-118. https://doi.org/10.1016/j.foodchem.2017.04.174
• Göksu, S., Naderi, A., Akbaba, Y., Kalin, P., Akincioǧlu, A., Gülçin, I., Durdagi, S., & Salmas, R. E. (2014). Carbonic anhydrase inhibitory properties of novel benzylsulfamides using molecular modeling and experimental studies. Bioorganic Chemistry, 56, 75-82. https://doi.org/10.1016/j.bioorg.2014.07.009
• Gondolova, G., Taslimi, P., Medjidov, A., Farzaliyev, V., Sujayev, A., Huseynova, M., Şahin, O., Yalçın, B., Turkan, F., & Gulçin, İ. (2018). Synthesis, crystal structure and biological evaluation of spectroscopic characterization of Ni(II) and Co(II) complexes with N-salicyloil-N′-maleoil-hydrazine as anticholinergic and antidiabetic agents. Journal of Biochemical and Molecular Toxicology, 32(9), e22197. https://doi.org/10.1002/jbt.22197
• Gul, H. I., Tugrak, M., Sakagami, H., Taslimi, P., Gulcin, I., & Supuran, C. T. (2016). Synthesis and bioactivity studies on new 4-(3-(4-substitutedphenyl)-3a,4-dihydro-3H-indeno[1,2-c]pyrazol-2-yl) benzenesulfonamides. Journal of Enzyme Inhibition and Medicinal Chemistry, 31(6), 1619-1624. https://doi.org/10.3109/14756366.2016.1160077
• Gülcin, İ., Scozzafava, A., Supuran, C. T., Koksal, Z., Turkan, F., Çetinkaya, S., Bingöl, Z., Huyut, Z., & Alwasel, S. H. (2016). Rosmarinic acid inhibits some metabolic enzymes including glutathione s-transferase, lactoperoxidase, acetylcholinesterase, butyrylcholinesterase and carbonic anhydrase isoenzymes. Journal of Enzyme Inhibition and Medicinal Chemistry, 31(6), 698-702. https://doi.org/10.3109/14756366.2015.1135914
• Gulcin, İ., Taslimi, P., Aygün, A., Sadeghian, N., Bastem, E., Kufrevioglu, O. I., Turkan, F., & Şen, F. (2018). Antidiabetic and antiparasitic potentials: Inhibition effects of some natural antioxidant compounds on α-glycosidase, α-amylase and human glutathione S-transferase enzymes. International Journal of Biological Macromolecules, 119, 741-746. https://doi.org/10.1016/j.ijbiomac.2018.08.001
• Gulcin, I., Kaya, R., Goren, A. C., Akincioglu, H., Topal, M., Bingol, Z., Cetin Çakmak, K., Ozturk Sarikaya, S. B., Durmaz, L., & Alwasel, S. (2019). Anticholinergic, antidiabetic and antioxidant activities of cinnamon (cinnamomum verum) bark extracts: polyphenol contents analysis by LC-MS/MS. International Journal of Food Properties, 22(1), 1511–1526. https://doi.org/10.1080/10942912.2019.1656232
• Hoff, E., Zou, D., Schiza, S., Demir, Y., Grote, L., Bouloukaki, I., Beydemir, Ş., Eskandari, D., Stenlöf, K., & Hedner, J. (2020). Carbonic anhydrase, obstructive sleep apnea and hypertension: effects of intervention. Journal of Sleep Research, 29(2), e12956. https://doi.org/10.1111/jsr.12956
• Hua, Q., Chen, C., Tel Zur, N., Wang, H., Wu, J., Chen, J., Zhang, Z., Zhao, J., Hu, G., & Qin, Y. (2018). Metabolomic characterization of pitaya fruit from three red-skinned cultivars with different pulp colors. Plant Physiology and Biochemistry, 126, 117-125. https://doi.org/10.1016/j.plaphy.2018.02.027
• Jalgaonkar, K., Mahawar, M. K., Bibwe, B., & Kannaujia, P. (2022). Postharvest profile, processing and waste utilization of dragon fruit (Hylocereus Spp.): A Review. In Food Reviews International, 38(4), 1-27. https://doi.org/10.1080/87559129.2020.1742152
• Jiang, H., Zhang, W., Li, X., Shu, C., Jiang, W., & Cao, J. (2021). Nutrition, phytochemical profile, bioactivities and applications in food industry of pitaya (Hylocereus spp.) peels: a comprehensive review. In Trends in Food Science and Technology, 116, 199-217. https://doi.org/10.1016/j.tifs.2021.06.040
• Joshi, M., & Prabhakar, B. (2020). Phytoconstituents and pharmaco-therapeutic benefits of pitaya: a wonder fruit. In Journal of Food Biochemistry, 44(7), e13260. https://doi.org/10.1111/jfbc.13260
• Kazancı, A., Gök, Y., Kaya, R., Aktaş, A., Taslimi, P., & Gülçin, İ. (2021). Synthesis, characterization and bioactivities of dative donor ligand N-heterocyclic carbene (NHC) precursors and their Ag(I)NHC coordination compounds. Polyhedron, 193, 114866. https://doi.org/10.1016/j.poly.2020.114866
• Kocyigit, U. M., Budak, Y., Gürdere, M. B., Ertürk, F., Yencilek, B., Taslimi, P., Gülçin, İ., & Ceylan, M. (2018). Synthesis of chalcone-imide derivatives and investigation of their anticancer and antimicrobial activities, carbonic anhydrase and acetylcholinesterase enzymes inhibition profiles. Archives of Physiology and Biochemistry, 124(1), 61-68. https://doi.org/10.1080/13813455.2017.1360914
• Madane, P., Das, A. K., Nanda, P. K., Bandyopadhyay, S., Jagtap, P., Shewalkar, A., & Maity, B. (2020). Dragon fruit (Hylocereus undatus) peel as antioxidant dietary fibre on quality and lipid oxidation of chicken nuggets. Journal of Food Science and Technology, 57(4), 1449-1461. https://doi.org/10.1007/s13197-019-04180-z
• Nar, M., Çetinkaya, Y., Gülçin, İ., & Menzek, A. (2013). (3,4-Dihydroxyphenyl)(2,3,4-trihydroxyphenyl)methanone and its derivatives as carbonic anhydrase isoenzymes inhibitors. Journal of Enzyme Inhibition and Medicinal Chemistry, 28(2), 402–406. https://doi.org/10.3109/14756366.2012.670807
• Ökten, S., Ekiz, M., Koçyiğit, Ü. M., Tutar, A., Çelik, İ., Akkurt, M., Gökalp, F., Taslimi, P., & Gülçin, İ. (2019). Synthesis, characterization, crystal structures, theoretical calculations and biological evaluations of novel substituted tacrine derivatives as cholinesterase and carbonic anhydrase enzymes inhibitors. Journal of Molecular Structure, e1175. https://doi.org/10.1016/j.molstruc.2018.08.063
• Öztaşkın, N., Kaya, R., Maraş, A., Şahin, E., Gülcin, İ., & Göksu, S. (2019). Synthesis and characterization of novel bromophenols: Determination of their anticholinergic, antidiabetic and antioxidant activities. Bioorganic Chemistry, 87, 91–102. https://doi.org/10.1016/j.bioorg.2019.03.010
• Ranilla, L. G., Kwon, Y. I., Apostolidis, E., & Shetty, K. (2010). Phenolic compounds, antioxidant activity and in vitro inhibitory potential against key enzymes relevant for hyperglycemia and hypertension of commonly used medicinal plants, herbs and spices in latin America. Bioresource Technology, 101(12), 4676-4689 https://doi.org/10.1016/j.biortech.2010.01.093
• Sever, B., Altıntop, M. D., Demir, Y., Akalın Çiftçi, G., Beydemir, Ş., & Özdemir, A. (2020). Design, synthesis, in vitro and in silico investigation of aldose reductase inhibitory effects of new thiazole-based compounds. Bioorganic Chemistry, 102, 104-110. https://doi.org/10.1016/j.bioorg.2020.104110
• Sever, B., Altlntop, M. D., Demir, Y., Türkeş, C., Özbaş, K., Çiftçi, G. A., Beydemir, S., & Özdemir, A. (2021). A new series of 2,4-thiazolidinediones endowed with potent aldose reductase inhibitory activity. Open Chemistry, 19(1), 347-357. https://doi.org/10.1515/chem-2021-0032
• Sever, B., Türkeş, C., Altıntop, M. D., Demir, Y., Akalın Çiftçi, G., & Beydemir, Ş. (2021). Novel metabolic enzyme inhibitors designed through the molecular hybridization of thiazole and pyrazoline scaffolds. Archiv Der Pharmazie, 354(12), e2100294. https://doi.org/10.1002/ardp.202100294
• Soto-Hernandez, M., Palma-Tenango & M., Garcia-Mateos, M., (Eds.). (2017). In Phenolic Compounds- Biological Activity. IntechOpen. https://doi.org/10.5772/66844
• Takim, K., Yigin, A., Koyuncu, I., Kaya, R., & Gülçin, İ. (2021). Anticancer, anticholinesterase and antidiabetic activities of tunceli garlic (allium tuncelianum): determining its phytochemical content by LC–MS/MS analysis. Journal of Food Measurement and Characterization, 15(4), 3323-3335. https://doi.org/10.1007/s11694-021-00912-y
• Tao, Y., Zhang, Y., Cheng, Y., & Wang, Y. (2013). Rapid screening and identification of α-glucosidase inhibitors from mulberry leaves using enzyme-immobilized magnetic beads coupled with HPLC/MS and NMR. Biomedical Chromatography, 27(2), 148-155. https://doi.org/10.1002/bmc.2761
• Taşkın, T., Kahvecioğlu, D., Türkoğlu, E. A., Doğan, A., & Kuzu, M. (2022). In vitro biological activities of different extracts from alcea dissecta. Clinical and Experimental Health Sciences., 12(1), 53-60. https://doi.org/10.33808/clinexphealthsci.787845
• Taslimi, P., Aslan, H. E., Demir, Y., Oztaskin, N., Maraş, A., Gulçin, İ., Beydemir, S., & Goksu, S. (2018). Diarylmethanon, bromophenol and diarylmethane compounds: discovery of potent aldose reductase, α-amylase and α-glycosidase inhibitors as new therapeutic approach in diabetes and functional hyperglycemia. International Journal of Biological Macromolecules, 119, 857-863. https://doi.org/10.1016/j.ijbiomac.2018.08.004
• Topal, M., & Gulcin, İ. (2022). Evaluation of the in vitro antioxidant, antidiabetic and anticholinergic properties of rosmarinic acid from rosemary (Rosmarinus officinalis L.). Biocatalysis and Agricultural Biotechnology, 43, e102417. https://doi.org/10.1016/j.bcab.2022.102417
• Verpoorte, J. A., Mehta, S., & Edsall, J. T. (1967). Esterase activities of human carbonic anhydrases B and C. Journal of Biological Chemistry, 242(18), 4221-4229. https://doi.org/10.1016/s0021-9258(18)95800-x
• Wong, Y. M., & Siow, L. F. (2015). Effects of heat, pH, antioxidant, agitation and light on betacyanin stability using red-fleshed dragon fruit (Hylocereus polyrhizus) juice and concentrate as models. Journal of Food Science and Technology, 52(5), 3086-3092. https://doi.org/10.1007/s13197-014-1362-2
• Yaşar, Ü., Gönül, İ., Türkeş, C., Demir, Y., & Beydemir, Ş. (2021). Transition-metal complexes of bidentate schiff-base ligands: ın vitro and ın silico evaluation as non-classical carbonic anhydrase and potential acetylcholinesterase ınhibitors. ChemistrySelect, 6(29), 7278-7284. https://doi.org/10.1002/slct.202102082
• Zaid, R. M., Mishra, P., Siti Noredyani, A. R., Tabassum, S., Ab Wahid, Z., & Mimi Sakinah, A. M. (2020). Proximate characteristics and statistical optimization of ultrasound-assisted extraction of high-methoxyl-pectin from hylocereus polyrhizus peels. Food and Bioproducts Processing, 123, 134-149. https://doi.org/10.1016/j.fbp.2020.06.011
• Zain, N. M., Nazeri, M. A., & Azman, N. A. (2019). Assessment on bioactive compounds and the effect of microwave on pitaya peel. Jurnal Teknologi, 81(2), 11-19. https://doi.org/10.11113/jt.v81.12847