Enfoques computacionales e inteligencia artificial para estudiar compuestos fenólicos alimentarios
DOI:
https://doi.org/10.29057/icap.v12iEspecial.15314Palabras clave:
Quimioinformática, acoplamiento, bioaccesibilidad, nutrigenómica, metabolómicaResumen
La caracterización funcional de los compuestos fenólicos en alimentos plantea desafíos derivados de su diversidad estructural, transformaciones metabólicas y comportamiento en matrices complejas. Este trabajo tuvo como objetivo examinar, mediante una revisión narrativa, el uso de inteligencia artificial para modelar su actividad biológica, considerando enfoques in vitro, in vivo e in silico. Se analizaron publicaciones recientes en las que se aplicaron redes neuronales artificiales, algoritmos de bosque aleatorio y técnicas de simulación molecular para predecir interacciones proteína-polifenol, propiedades bioactivas y formulaciones funcionales. La información fue sistematizada considerando la estructura química, la bioaccesibilidad, los blancos moleculares y el impacto fisiológico. Los resultados sugieren que los modelos de inteligencia artificial (IA) permiten integrar grandes volúmenes de datos multivariados y generar predicciones útiles, aunque persisten limitaciones relacionadas con la interpretación de los modelos y la validación empírica. Se concluye que la IA puede contribuir al diseño computacional de alimentos funcionales mediante una predicción más eficiente del comportamiento bioactivo de los compuestos fenólicos.
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[1] De Camargo AC, Schwember AR, Parada R, Garcia S, Maróstica Júnior MR, Franchin M, et al. Opinion on the Hurdles and Potential Health Benefits in Value-Added Use of Plant Food Processing By-Products as Sources of Phenolic Compounds. Int J Mol Sci 2018;19:3498. https://doi.org/10.3390/ijms19113498.
[2] Lin D, Xiao M, Zhao J, Li Z, Xing B, Li X, et al. An Overview of Plant Phenolic Compounds and Their Importance in Human Nutrition and Management of Type 2 Diabetes. Molecules 2016;21:1374. https://doi.org/10.3390/molecules21101374.
[3] Haghi G, Hatami A. Simultaneous Quantification of Flavonoids and Phenolic Acids in Plant Materials by a Newly Developed Isocratic High-Performance Liquid Chromatography Approach. J Agric Food Chem 2010;58:10812–6. https://doi.org/10.1021/jf102175x.
[4] Ribas-Agustí A, Martín-Belloso O, Soliva-Fortuny R, Elez-Martínez P. Food processing strategies to enhance phenolic compounds bioaccessibility and bioavailability in plant-based foods. Crit Rev Food Sci Nutr 2018;58:2531–48. https://doi.org/10.1080/10408398.2017.1331200.
[5] Gulsunoglu-Konuskan Z, Kilic-Akyilmaz M. Microbial Bioconversion of Phenolic Compounds in Agro-industrial Wastes: A Review of Mechanisms and Effective Factors. J Agric Food Chem 2022;70:6901–10. https://doi.org/10.1021/acs.jafc.1c06888.
[6] Velderrain-Rodríguez GR, Palafox-Carlos H, Wall-Medrano A, Ayala-Zavala JF, Chen C-YO, Robles-Sánchez M, et al. Phenolic compounds: their journey after intake. Food Funct 2014;5:189–97. https://doi.org/10.1039/C3FO60361J.
[7] Vichapong J, Sookserm M, Srijesdaruk V, Swatsitang P, Srijaranai S. High performance liquid chromatographic analysis of phenolic compounds and their antioxidant activities in rice varieties. LWT - Food Sci Technol 2010;43:1325–30. https://doi.org/10.1016/j.lwt.2010.05.007.
[8] Altuner EM, Tokuşoğlu Ö. The effect of high hydrostatic pressure processing on the extraction, retention and stability of anthocyanins and flavonols contents of berry fruits and berry juices. Int J Food Sci Technol 2013;48:1991–7. https://doi.org/10.1111/ijfs.12185.
[9] Pinarli B, Simge Karliga E, Ozkan G, Capanoglu E. Interaction of phenolics with food matrix: In vitro and in vivo approaches. Mediterr J Nutr Metab 2020;13:63–74. https://doi.org/10.3233/MNM-190362.
[10] Sęczyk Ł, Gawlik-Dziki U, Świeca M. Influence of Phenolic-Food Matrix Interactions on In Vitro Bioaccessibility of Selected Phenolic Compounds and Nutrients Digestibility in Fortified White Bean Paste. Antioxidants 2021;10:1825. https://doi.org/10.3390/antiox10111825.
[11] Delgado RM, Hidalgo FJ, Zamora R. Antagonism between lipid-derived reactive carbonyls and phenolic compounds in the Strecker degradation of amino acids. Food Chem 2016;194:1143–8. https://doi.org/10.1016/j.foodchem.2015.07.126.
[12] Fernando IPS, Kim M, Son K-T, Jeong Y, Jeon Y-J. Antioxidant Activity of Marine Algal Polyphenolic Compounds: A Mechanistic Approach. J Med Food 2016;19:615–28. https://doi.org/10.1089/jmf.2016.3706.
[13] Rahimi M, Kordrostami M, Mohamadhasani F, Chaeikar SS. Antioxidant gene expression analysis and evaluation of total phenol content and oxygen-scavenging system in tea accessions under normal and drought stress conditions. BMC Plant Biol 2021;21:494. https://doi.org/10.1186/s12870-021-03275-0.
[14] Grabska-Kobylecka I, Kaczmarek-Bak J, Figlus M, Prymont-Przyminska A, Zwolinska A, Sarniak A, et al. The Presence of Caffeic Acid in Cerebrospinal Fluid: Evidence That Dietary Polyphenols Can Cross the Blood-Brain Barrier in Humans. Nutrients 2020;12:1531. https://doi.org/10.3390/nu12051531.
[15] Nájera-Maldonado JM, Salazar R, Alvarez-Fitz P, Acevedo-Quiroz M, Flores-Alfaro E, Hernández-Sotelo D, et al. Phenolic Compounds of Therapeutic Interest in Neuroprotection. J Xenobiotics 2024;14:227–46. https://doi.org/10.3390/jox14010014.
[16] Aliyu A, Musa D, Egharevba H. Bioactive chemical compounds and pharmacological prospect of Mitracarpus villosus (Swartz) DC- a review. Asian J Biochem Pharm Res 2017;7. https://doi.org/10.24214/AJBPR/7/2/99113.
[17] Mutha RE, Tatiya AU, Surana SJ. Flavonoids as natural phenolic compounds and their role in therapeutics: an overview. Future J Pharm Sci 2021;7:25. https://doi.org/10.1186/s43094-020-00161-8.
[18] Li H, Jiang Y, Yang J, Pang R, Chen Y, Mo L, et al. Preparation of curcumin-chitosan composite film with high antioxidant and antibacterial capacity: Improving the solubility of curcumin by encapsulation of biopolymers. Food Hydrocoll 2023;145:109150. https://doi.org/10.1016/j.foodhyd.2023.109150.
[19] Odriozola-Serrano I, Nogueira DP, Esparza I, Vaz AA, Jiménez-Moreno N, Martín-Belloso O, et al. Stability and Bioaccessibility of Phenolic Compounds in Rosehip Extracts during In Vitro Digestion. Antioxidants 2023;12:1035. https://doi.org/10.3390/antiox12051035.
[20] Demir Y, Işık M, Gülçin İ, Beydemir Ş. Phenolic compounds inhibit the aldose reductase enzyme from the sheep kidney: DEMIR ET AL. J Biochem Mol Toxicol 2017;31:e21936. https://doi.org/10.1002/jbt.21935.
[21] Eseberri I, Trepiana J, Léniz A, Gómez-García I, Carr-Ugarte H, González M, et al. Variability in the Beneficial Effects of Phenolic Compounds: A Review. Nutrients 2022;14:1925. https://doi.org/10.3390/nu14091925.
[22] Śliwińska AA, Sykłowska-Baranek K, Kośmider A, Granica S, Miszczak K, Nowicka G, et al. Stimulation of phenolic compounds production in the in vitro cultivated Polyscias filicifolia Bailey shoots and evaluation of the antioxidant and cytotoxic potential of plant extracts. Acta Soc Bot Pol 2018;87. https://doi.org/10.5586/asbp.3586.
[23] Rodríguez-Pérez R, Bajorath J. Feature importance correlation from machine learning indicates functional relationships between proteins and similar compound binding characteristics. Sci Rep 2021;11:14245. https://doi.org/10.1038/s41598-021-93771-y.
[24] Meng X-Y, Zhang H-X, Mezei M, Cui M. Molecular Docking: A Powerful Approach for Structure-Based Drug Discovery. Curr Comput Aided-Drug Des 2011;7:146–57. https://doi.org/10.2174/157340911795677602.
[25] Bai X, Zhou L, Zhou L, Cang S, Liu Y, Liu R, et al. The Research Progress of Extraction, Purification and Analysis Methods of Phenolic Compounds from Blueberry: A Comprehensive Review. Molecules 2023;28:3610. https://doi.org/10.3390/molecules28083610.
[26] Vieira RV, Peiter GC, De Melo FF, Zarpelon-Schutz AC, Teixeira KN. In silico prospective analysis of the medicinal plants activity on the CagA oncoprotein from Helicobacter pylori. World J Clin Oncol 2024;15:653–63. https://doi.org/10.5306/wjco.v15.i5.653.
[27] Brown N, Ertl P, Lewis R, Luksch T, Reker D, Schneider N. Artificial intelligence in chemistry and drug design. J Comput Aided Mol Des 2020;34:709–15. https://doi.org/10.1007/s10822-020-00317-x.
[28] Ma E, Jin L, Qian C, Feng C, Zhao Z, Tian H, et al. Bioinformatics-Guided Identification of Ethyl Acetate Extract of Citri Reticulatae Pericarpium as a Functional Food Ingredient with Anti-Inflammatory Potential. Molecules 2022;27:5435. https://doi.org/10.3390/molecules27175435.
[29] Lin K, Yang Y, Cheng F. A Molecular Image-based Explainable Artificial intelligence Framework Identifies Novel Candidate Antibiotics 2024. https://doi.org/10.1101/2024.07.21.604494.
[30] Prelaj A, Galli EG, Miskovic V, Pesenti M, Viscardi G, Pedica B, et al. Real-world data to build explainable trustworthy artificial intelligence models for prediction of immunotherapy efficacy in NSCLC patients. Front Oncol 2023;12:1078822. https://doi.org/10.3389/fonc.2022.1078822.
[31] Spiegel M, Kapusta K, Kołodziejczyk W, Saloni J, Żbikowska B, Hill GA, et al. Antioxidant Activity of Selected Phenolic Acids–Ferric Reducing Antioxidant Power Assay and QSAR Analysis of the Structural Features. Molecules 2020;25:3088. https://doi.org/10.3390/molecules25133088.
[32] Trepiana J, Krisa S, Portillo MP. Activity of Pterostilbene Metabolites against Liver Steatosis in Cultured Hepatocytes. Molecules 2020;25:5444. https://doi.org/10.3390/molecules25225444.
[33] Montenegro MF, Teruel JA, García-Molina P, Tudela J, Rodríguez-López JN, García-Cánovas F, et al. Molecular Docking Studies of Ortho-Substituted Phenols to Tyrosinase Helps Discern If a Molecule Can Be an Enzyme Substrate. Int J Mol Sci 2024;25:6891. https://doi.org/10.3390/ijms25136891.
[34] Synowiec A, Żyła K, Gniewosz M, Kieliszek M. An effect of positional isomerism of benzoic acid derivatives on antibacterial activity against Escherichia coli. Open Life Sci 2021;16:594–601. https://doi.org/10.1515/biol-2021-0060.
[35] Ampofo J, Ngadi M. Novel Non-Thermal Processing Technologies: Impact on Food Phenolic Compounds during Processing. In: A. Badria F, editor. Biochemistry, vol. 26, IntechOpen; 2022. https://doi.org/10.5772/intechopen.98688.
[36] Dias M, Romaní-Pérez M, Romaní A, De La Cruz A, Pastrana L, Fuciños P, et al. Recent Technological Advances in Phenolic Compounds Recovery and Applications: Source of Nutraceuticals for the Management of Diabetes. Appl Sci 2022;12:9271. https://doi.org/10.3390/app12189271.
[37] Maqsood S, Benjakul S, Abushelaibi A, Alam A. Phenolic Compounds and Plant Phenolic Extracts as Natural Antioxidants in Prevention of Lipid Oxidation in Seafood: A Detailed Review. Compr Rev Food Sci Food Saf 2014;13:1125–40. https://doi.org/10.1111/1541-4337.12106.
[38] Tsao R. Chemistry and Biochemistry of Dietary Polyphenols. Nutrients 2010;2:1231–46. https://doi.org/10.3390/nu2121231.
[39] Melini V, Melini F, Acquistucci R. Phenolic Compounds and Bioaccessibility Thereof in Functional Pasta. Antioxidants 2020;9:343. https://doi.org/10.3390/antiox9040343.
[40] Li J, Lu X, Zou X, Ye B-C. Recent Advances in Microbial Metabolic Engineering for Production of Natural Phenolic Acids. J Agric Food Chem 2024;72:4538–51. https://doi.org/10.1021/acs.jafc.3c07658.
[41] Zeng Z, Liu C, Luo S, Chen J, Gong E. The Profile and Bioaccessibility of Phenolic Compounds in Cereals Influenced by Improved Extrusion Cooking Treatment. PLOS ONE 2016;11:e0161086. https://doi.org/10.1371/journal.pone.0161086.
[42] Czubinski J, Dwiecki K. A review of methods used for investigation of protein–phenolic compound interactions. Int J Food Sci Technol 2017;52:573–85. https://doi.org/10.1111/ijfs.13339.
[43] Abeywickrama G, Debnath SC, Ambigaipalan P, Shahidi F. Phenolics of Selected Cranberry Genotypes ( Vaccinium Macrocarpon Ait.) and Their Antioxidant Efficacy. J Agric Food Chem 2016;64:9342–51. https://doi.org/10.1021/acs.jafc.6b04291.
[44] Razem M, Ding Y, Morozova K, Mazzetto F, Scampicchio M. Analysis of Phenolic Compounds in Food by Coulometric Array Detector: A Review. Sensors 2022;22:7498. https://doi.org/10.3390/s22197498.
[45] Külen O, Stushnoff C, Holm DG. Effect of cold storage on total phenolics content, antioxidant activity and vitamin C level of selected potato clones. J Sci Food Agric 2013;93:2437–44. https://doi.org/10.1002/jsfa.6053.
[46] Bendary E, Francis RR, Ali HMG, Sarwat MI, El Hady S. Antioxidant and structure–activity relationships (SARs) of some phenolic and anilines compounds. Ann Agric Sci 2013;58:173–81. https://doi.org/10.1016/j.aoas.2013.07.002.
[47] Kokkinidou S, Peterson DG. Control of Maillard-Type Off-Flavor Development in Ultrahigh-Temperature-Processed Bovine Milk by Phenolic Chemistry. J Agric Food Chem 2014;62:8023–33. https://doi.org/10.1021/jf501919y.
[48] Ávila-Gálvez MÁ, Espín JC, González-Sarrías A. Physiological Relevance of the Antiproliferative and Estrogenic Effects of Dietary Polyphenol Aglycones versus Their Phase-II Metabolites on Breast Cancer Cells: A Call of Caution. J Agric Food Chem 2018;66:8547–55. https://doi.org/10.1021/acs.jafc.8b03100.
[49] Koudoufio M, Desjardins Y, Feldman F, Spahis S, Delvin E, Levy E. Insight into Polyphenol and Gut Microbiota Crosstalk: Are Their Metabolites the Key to Understand Protective Effects against Metabolic Disorders? Antioxidants 2020;9:982. https://doi.org/10.3390/antiox9100982.
[50] Monagas M, Urpi-Sarda M, Sánchez-Patán F, Llorach R, Garrido I, Gómez-Cordovés C, et al. Insights into the metabolism and microbial biotransformation of dietary flavan-3-ols and the bioactivity of their metabolites. Food Funct 2010;1:233. https://doi.org/10.1039/c0fo00132e.
[51] Zhang H, Yu Y, Zhang H, Zhao X, Wang J. A comprehensive profiling of phenolic compounds and antioxidant activities of 24 varieties of red raspberry cultivated in Northeast China. J Food Sci 2025;90:e17623. https://doi.org/10.1111/1750-3841.17623.
[52] Di Lorenzo C, Colombo F, Biella S, Stockley C, Restani P. Polyphenols and Human Health: The Role of Bioavailability. Nutrients 2021;13:273. https://doi.org/10.3390/nu13010273.
[53] Pietrek LM, Stelzl LS, Hummer G. Structural ensembles of disordered proteins from hierarchical chain growth and simulation. Curr Opin Struct Biol 2023;78:102501.
[54] Silva S, Veiga M, Costa EM, Oliveira ALS, Madureira AR, Pintado M. Nanoencapsulation of Polyphenols towards Dairy Beverage Incorporation. Beverages 2018;4:61. https://doi.org/10.3390/beverages4030061.
[55] Vaz A, Odriozola-Serrano I, Oms-Oliu G, Martín-Belloso O. Physicochemical Properties and Bioaccessibility of Phenolic Compounds of Dietary Fibre Concentrates from Vegetable By-Products. Foods 2022;11:2578. https://doi.org/10.3390/foods11172578.
[56] Gómez-Juaristi M, Sarria B, Martínez-López S, Bravo Clemente L, Mateos R. Flavanol Bioavailability in Two Cocoa Products with Different Phenolic Content. A Comparative Study in Humans. Nutrients 2019;11:1441. https://doi.org/10.3390/nu11071441.
[57] Zhang H, Zheng J, Liu X, Ding Q, Jiang L, Guo H, et al. Milk protein and fat play different roles in affecting the bioavailability and the antioxidant activity of jujube juice phenolics in rats. Mol Nutr Food Res 2012;56:1511–9. https://doi.org/10.1002/mnfr.201200085.
[58] Grgić J, Šelo G, Planinić M, Tišma M, Bucić-Kojić A. Role of the Encapsulation in Bioavailability of Phenolic Compounds. Antioxidants 2020;9:923. https://doi.org/10.3390/antiox9100923.
[59] Polia F, Pastor-Belda M, Martínez-Blázquez A, Horcajada M-N, Tomás-Barberán FA, García-Villalba R. Technological and Biotechnological Processes To Enhance the Bioavailability of Dietary (Poly)phenols in Humans. J Agric Food Chem 2022;70:2092–107. https://doi.org/10.1021/acs.jafc.1c07198.
[60] Redan BW, Buhman KK, Novotny JA, Ferruzzi MG. Altered Transport and Metabolism of Phenolic Compounds in Obesity and Diabetes: Implications for Functional Food Development and Assessment. Adv Nutr 2016;7:1090–104. https://doi.org/10.3945/an.116.013029.
[61] Ribas-Agustí A, Martín-Belloso O, Soliva-Fortuny R, Elez-Martínez P. Influence of pulsed electric fields processing on the bioaccessible and non-bioaccessible fractions of apple phenolic compounds. J Funct Foods 2019;59:206–14. https://doi.org/10.1016/j.jff.2019.05.041.
[62] Erskine E, Gültekin Subaşı B, Vahapoglu B, Capanoglu E. Coffee Phenolics and Their Interaction with Other Food Phenolics: Antagonistic and Synergistic Effects. ACS Omega 2022;7:1595–601. https://doi.org/10.1021/acsomega.1c06085.
[63] Palafox-Carlos H, Gil-Chávez J, Sotelo-Mundo RR, Namiesnik J, Gorinstein S, González-Aguilar GA. Antioxidant Interactions between Major Phenolic Compounds Found in ‘Ataulfo’ Mango Pulp: Chlorogenic, Gallic, Protocatechuic and Vanillic Acids. Molecules 2012;17:12657–64. https://doi.org/10.3390/molecules171112657.
[64] Dudonné S, Dubé P, Pilon G, Marette A, Jacques H, Weisnagel J, et al. Modulation of Strawberry/Cranberry Phenolic Compounds Glucuronidation by Co-Supplementation with Onion: Characterization of Phenolic Metabolites in Rat Plasma Using an Optimized μSPE–UHPLC-MS/MS Method. J Agric Food Chem 2014;62:3244–56. https://doi.org/10.1021/jf404965z.
[65] Nieto JA, Fernández-Jalao I, Siles-Sánchez MDLN, Santoyo S, Jaime L. Implication of the Polymeric Phenolic Fraction and Matrix Effect on the Antioxidant Activity, Bioaccessibility, and Bioavailability of Grape Stem Extracts. Molecules 2023;28:2461. https://doi.org/10.3390/molecules28062461.
[66] Palafox‐Carlos H, Ayala‐Zavala JF, González‐Aguilar GA. The Role of Dietary Fiber in the Bioaccessibility and Bioavailability of Fruit and Vegetable Antioxidants. J Food Sci 2011;76. https://doi.org/10.1111/j.1750-3841.2010.01957.x.
[67] Cortés‐Martín A, Selma MV, Tomás‐Barberán FA, González‐Sarrías A, Espín JC. Where to Look into the Puzzle of Polyphenols and Health? The Postbiotics and Gut Microbiota Associated with Human Metabotypes. Mol Nutr Food Res 2020;64:1900952. https://doi.org/10.1002/mnfr.201900952.
[68] Draijer R, Van Dorsten F, Zebregs Y, Hollebrands B, Peters S, Duchateau G, et al. Impact of Proteins on the Uptake, Distribution, and Excretion of Phenolics in the Human Body. Nutrients 2016;8:814. https://doi.org/10.3390/nu8120814.
[69] Van Dorsten FA, Peters S, Gross G, Gomez-Roldan V, Klinkenberg M, De Vos RC, et al. Gut Microbial Metabolism of Polyphenols from Black Tea and Red Wine/Grape Juice Is Source-Specific and Colon-Region Dependent. J Agric Food Chem 2012;60:11331–42. https://doi.org/10.1021/jf303165w.
[70] Williamson G, Kay CD, Crozier A. The Bioavailability, Transport, and Bioactivity of Dietary Flavonoids: A Review from a Historical Perspective. Compr Rev Food Sci Food Saf 2018;17:1054–112. https://doi.org/10.1111/1541-4337.12351.
[71] Guasch-Ferré M, Merino J, Sun Q, Fitó M, Salas-Salvadó J. Dietary Polyphenols, Mediterranean Diet, Prediabetes, and Type 2 Diabetes: A Narrative Review of the Evidence. Oxid Med Cell Longev 2017;2017:6723931. https://doi.org/10.1155/2017/6723931.
[72] Escobar‐Martínez I, Arreaza‐Gil V, Muguerza B, Arola‐Arnal A, Bravo FI, Torres‐Fuentes C, et al. Administration Time Significantly Affects Plasma Bioavailability of Grape Seed Proanthocyanidins Extract in Healthy and Obese Fischer 344 Rats. Mol Nutr Food Res 2022;66:2100552. https://doi.org/10.1002/mnfr.202100552.
[73] Rothwell JA, Urpi-Sarda M, Boto-Ordonez M, Knox C, Llorach R, Eisner R, et al. Phenol-Explorer 2.0: a major update of the Phenol-Explorer database integrating data on polyphenol metabolism and pharmacokinetics in humans and experimental animals. Database 2012;2012:bas031–bas031. https://doi.org/10.1093/database/bas031.
[74] He F, Bian Y, Zhao Y, Xia M, Liu S, Gui J, et al. In vitro conversion of ellagic acid to urolithin A by different gut microbiota of urolithin metabotype A. Appl Microbiol Biotechnol 2024;108:215. https://doi.org/10.1007/s00253-024-13061-1.
[75] Choi SR, Lee H, Singh D, Cho D, Chung J-O, Roh J-H, et al. Bidirectional Interactions between Green Tea (GT) Polyphenols and Human Gut Bacteria. J Microbiol Biotechnol 2023;33:1317–28. https://doi.org/10.4014/jmb.2306.06014.
[76] Khine WWT, Haldar S, De Loi S, Lee Y-K. A single serving of mixed spices alters gut microflora composition: a dose–response randomised trial. Sci Rep 2021;11:11264. https://doi.org/10.1038/s41598-021-90453-7.
[77] Lin H, Meng L, Sun Z, Sun S, Huang X, Lin N, et al. Yellow Wine Polyphenolic Compound Protects Against Doxorubicin-Induced Cardiotoxicity by Modulating the Composition and Metabolic Function of the Gut Microbiota. Circ Heart Fail 2021;14:e008220. https://doi.org/10.1161/CIRCHEARTFAILURE.120.008220.
[78] Haș IM, Tit DM, Bungau SG, Pavel FM, Teleky B-E, Vodnar DC, et al. Cardiometabolic Risk: Characteristics of the Intestinal Microbiome and the Role of Polyphenols. Int J Mol Sci 2023;24:13757. https://doi.org/10.3390/ijms241813757.
[79] Cano R, Bermúdez V, Galban N, Garrido B, Santeliz R, Gotera MP, et al. Dietary Polyphenols and Gut Microbiota Cross-Talk: Molecular and Therapeutic Perspectives for Cardiometabolic Disease: A Narrative Review. Int J Mol Sci 2024;25:9118. https://doi.org/10.3390/ijms25169118.
[80] Pasinetti GM, Singh R, Westfall S, Herman F, Faith J, Ho L. The Role of the Gut Microbiota in the Metabolism of Polyphenols as Characterized by Gnotobiotic Mice. In: Pasinetti GM, editor. Adv. Alzheimer’s Dis., IOS Press; 2022. https://doi.org/10.3233/AIAD220014.
[81] Sorrenti V, Ali S, Mancin L, Davinelli S, Paoli A, Scapagnini G. Cocoa Polyphenols and Gut Microbiota Interplay: Bioavailability, Prebiotic Effect, and Impact on Human Health. Nutrients 2020;12:1908. https://doi.org/10.3390/nu12071908.
[82] Nemzer BV, Al-Taher F, Kalita D, Yashin AY, Yashin YI. Health-Improving Effects of Polyphenols on the Human Intestinal Microbiota: A Review. Int J Mol Sci 2025;26:1335. https://doi.org/10.3390/ijms26031335.
[83] Salawu SO, Bester MJ, Duodu KG. Phenolic Composition and Bioactive Properties of Cell Wall Preparations and Whole Grains of Selected Cereals and Legumes: Bioactives of Cereal and Legume Cell Walls. J Food Biochem 2014;38:62–72. https://doi.org/10.1111/jfbc.12026.
[84] Bhavya SN, Prakash J. Nutritional properties of iron fortified flatbreads enriched with greens and legumes. J Food Process Preserv 2021;45. https://doi.org/10.1111/jfpp.15495.
[85] Sevilla MTE, Martínez CJ, Cardador-Martínez A. Phenolic Compounds in Cereals and Legumes. In: Nollet LML, Gutierrez-Uribe JA, editors. Phenolic Compd. Food. 1st ed., Boca Raton : CRC Press, Taylor & Francis Group, 2018.: CRC Press; 2018, p. 319–32. https://doi.org/10.1201/9781315120157-16.
[86] Horvat D, Šimić G, Drezner G, Lalić A, Ledenčan T, Tucak M, et al. Phenolic Acid Profiles and Antioxidant Activity of Major Cereal Crops. Antioxidants 2020;9:527. https://doi.org/10.3390/antiox9060527.
[87] Kandil A, Li J, Vasanthan T, Bressler DC. Phenolic Acids in Some Cereal Grains and Their Inhibitory Effect on Starch Liquefaction and Saccharification. J Agric Food Chem 2012;60:8444–9. https://doi.org/10.1021/jf3000482.
[88] Malunga LN, Joseph Thandapilly S, Ames N. Cereal‐derived phenolic acids and intestinal alpha glucosidase activity inhibition: Structural activity relationship. J Food Biochem 2018;42:e12635. https://doi.org/10.1111/jfbc.12635.
[89] Hefni ME, Amann LS, Witthöft CM. A HPLC-UV Method for the Quantification of Phenolic Acids in Cereals. Food Anal Methods 2019;12:2802–12. https://doi.org/10.1007/s12161-019-01637-x.
[90] Shahidi F, Yeo J. Insoluble-Bound Phenolics in Food. Molecules 2016;21:1216. https://doi.org/10.3390/molecules21091216.
[91] Balli D, Bellumori M, Paoli P, Pieraccini G, Di Paola M, De Filippo C, et al. Study on a Fermented Whole Wheat: Phenolic Content, Activity on PTP1B Enzyme and In Vitro Prebiotic Properties. Molecules 2019;24:1120. https://doi.org/10.3390/molecules24061120.
[92] Zavala-López M, García-Lara S. An improved microscale method for extraction of phenolic acids from maize. Plant Methods 2017;13:81. https://doi.org/10.1186/s13007-017-0235-x.
[93] Montesano V, Negro D, De Lisi A, Urbano M, Sarli G, Laghetti G. Agronomic performance and phenolic profile of Tritordeum (x Tritordeum martinii A. Pujadas) lines. Cereal Chem 2021;98:382–91. https://doi.org/10.1002/cche.10378.
[94] Giusti F, Capuano E, Sagratini G, Pellegrini N. A comprehensive investigation of the behaviour of phenolic compounds in legumes during domestic cooking and in vitro digestion. Food Chem 2019;285:458–67. https://doi.org/10.1016/j.foodchem.2019.01.148.
[95] Rasera GB, De Camargo AC, De Castro RJS. Bioaccessibility of phenolic compounds using the standardized INFOGEST protocol: A narrative review. Compr Rev Food Sci Food Saf 2023;22:260–86. https://doi.org/10.1111/1541-4337.13065.
[96] Ribeiro L, Barros Santos MC, P. Gomes PW, Fernández-Ochoa Á, Simões Larraz Ferreira M. Overview of the Metabolite Composition and Antioxidant Capacity of Seven Major and Minor Cereal Crops and Their Milling Fractions. J Agric Food Chem 2024;72:19197–218. https://doi.org/10.1021/acs.jafc.4c01312.
[97] Fonteles TV, Maia DLH, Santos BN, Fernandes FAN, Rodrigues S, Campelo P. Nonthermal Processing as a Tool to Enhance Fruit Juice Bioactive Compounds’ Bioaccessibility. Processes 2024;12:1640. https://doi.org/10.3390/pr12081640.
[98] Kerienė I, Mankevičienė A, Bliznikas S, Jablonskytė-Raščė D, Maikštėnienė S, Česnulevičienė R. Biologically active phenolic compounds in buckwheat, oats and winter spelt wheat. Zemdirb-Agric 2015;102:289–96. https://doi.org/10.13080/z-a.2015.102.037.
[99] Khakimov B, Jespersen B, Engelsen S. Comprehensive and Comparative Metabolomic Profiling of Wheat, Barley, Oat and Rye Using Gas Chromatography-Mass Spectrometry and Advanced Chemometrics. Foods 2014;3:569–85. https://doi.org/10.3390/foods3040569.
[100] Shahidi F, Vamadevan V, Oh WY, Peng H. Phenolic compounds in agri-food by-products, their bioavailability and health effects. J Food Bioact 2019:57–119. https://doi.org/10.31665/JFB.2019.5178.
[101] Hole AS, Rud I, Grimmer S, Sigl S, Narvhus J, Sahlstrøm S. Improved Bioavailability of Dietary Phenolic Acids in Whole Grain Barley and Oat Groat following Fermentation with Probiotic Lactobacillus acidophilus, Lactobacillus johnsonii, and Lactobacillus reuteri. J Agric Food Chem 2012;60:6369–75. https://doi.org/10.1021/jf300410h.
[102] N’Dri D, Mazzeo T, Zaupa M, Ferracane R, Fogliano V, Pellegrini N. Effect of cooking on the total antioxidant capacity and phenolic profile of some whole‐meal African cereals. J Sci Food Agric 2013;93:29–36. https://doi.org/10.1002/jsfa.5837.
[103] Wang R, Li M, Brennan MA, Dhital S, Kulasiri D, Brennan CS, et al. Complexation of starch and phenolic compounds during food processing and impacts on the release of phenolic compounds. Compr Rev Food Sci Food Saf 2023;22:3185–211. https://doi.org/10.1111/1541-4337.13180.
[104] Ben Alaya I, Alves G, Lopes J, Silva LR. Use of Encapsulated Polyphenolic Compounds in Health Promotion and Disease Prevention: Challenges and Opportunities. Macromol 2024;4:805–42. https://doi.org/10.3390/macromol4040048.
[105] Cañas S, Rebollo-Hernanz M, Braojos C, Benítez V, Ferreras-Charro R, Dueñas M, et al. Understanding the Gastrointestinal Behavior of the Coffee Pulp Phenolic Compounds under Simulated Conditions. Antioxidants 2022;11:1818. https://doi.org/10.3390/antiox11091818.
[106] Zhu Y, Yang S, Huang Y, Huang J, Li Y. Effect of in vitro gastrointestinal digestion on phenolic compounds and antioxidant properties of soluble and insoluble dietary fibers derived from hulless barley. J Food Sci 2021;86:628–34. https://doi.org/10.1111/1750-3841.15592.
[107] Strauch RC, Lila MA. Pea protein isolate characteristics modulate functional properties of pea protein–cranberry polyphenol particles. Food Sci Nutr 2021;9:3740–51. https://doi.org/10.1002/fsn3.2335.
[108] Virtanen V, Green RJ, Karonen M. Interactions between Hydrolysable Tannins and Lipid Vesicles from Escherichia coli with Isothermal Titration Calorimetry. Molecules 2022;27:3204. https://doi.org/10.3390/molecules27103204.
[109] Pineda-Vadillo C, Nau F, Dubiard CG, Cheynier V, Meudec E, Sanz-Buenhombre M, et al. In vitro digestion of dairy and egg products enriched with grape extracts: Effect of the food matrix on polyphenol bioaccessibility and antioxidant activity. Food Res Int 2016;88:284–92. https://doi.org/10.1016/j.foodres.2016.01.029.
[110] Schmidt D, Wohlers A, Kuhnert N. Promiscuity in Polyphenol–Protein Interactions—Monitoring Protein Conformational Change upon Polyphenol–Protein Binding by Nano-Differential Fluorimetry (Nano-DSF). Molecules 2025;30:965. https://doi.org/10.3390/molecules30040965.
[111] Karonen M. Insights into Polyphenol–Lipid Interactions: Chemical Methods, Molecular Aspects and Their Effects on Membrane Structures. Plants 2022;11:1809. https://doi.org/10.3390/plants11141809.
[112] Ma J, Zheng Y, Tang W, Yan W, Nie H, Fang J, et al. Dietary polyphenols in lipid metabolism: A role of gut microbiome. Anim Nutr 2020;6:404–9. https://doi.org/10.1016/j.aninu.2020.08.002.
[113] Yahfoufi N, Alsadi N, Jambi M, Matar C. The Immunomodulatory and Anti-Inflammatory Role of Polyphenols. Nutrients 2018;10:1618. https://doi.org/10.3390/nu10111618.
[114] Fernandez-Panchon MS, Villano D, Troncoso AM, Garcia-Parrilla MC. Antioxidant Activity of Phenolic Compounds: From In Vitro Results to In Vivo Evidence. Crit Rev Food Sci Nutr 2008;48:649–71. https://doi.org/10.1080/10408390701761845.
[115] Ożarowski M, Pietrowiak A, Gryszczyńska A, Chaves DSDA, Krajewska-Patan A, Wielgus K, et al. Comparison of in vitro antioxidative activities of crude methanolic extracts of three species of Passiflora from greenhouse using DPPH, ABTS and FRAP methods. Herba Pol 2019;65:10–21. https://doi.org/10.2478/hepo-2019-0014.
[116] Li S, Shah NP. Effects of Various Heat Treatments on Phenolic Profiles and Antioxidant Activities of Pleurotus eryngii Extracts. J Food Sci 2013;78. https://doi.org/10.1111/1750-3841.12189.
[117] Figueiredo EAD, Alves NFB, Monteiro MMDO, Cavalcanti CDO, Silva TMSD, Silva TMGD, et al. Antioxidant and Antihypertensive Effects of a Chemically Defined Fraction of Syrah Red Wine on Spontaneously Hypertensive Rats. Nutrients 2017;9:574. https://doi.org/10.3390/nu9060574.
[118] Ferrer-Gallego R, Hernández-Hierro JM, Brás NF, Vale N, Gomes P, Mateus N, et al. Interaction between Wine Phenolic Acids and Salivary Proteins by Saturation-Transfer Difference Nuclear Magnetic Resonance Spectroscopy (STD-NMR) and Molecular Dynamics Simulations. J Agric Food Chem 2017;65:6434–41. https://doi.org/10.1021/acs.jafc.6b05414.
[119] Zhang D, Zhu P, Han L, Chen X, Liu H, Sun B. Highland Barley and Its By-Products Enriched with Phenolic Compounds for Inhibition of Pyrraline Formation by Scavenging α-Dicarbonyl Compounds. Foods 2021;10:1109. https://doi.org/10.3390/foods10051109.
[120] Wu J, Xue W, Voth GA. K -Means Clustering Coarse-Graining (KMC-CG): A Next Generation Methodology for Determining Optimal Coarse-Grained Mappings of Large Biomolecules. J Chem Theory Comput 2023;19:8987–97. https://doi.org/10.1021/acs.jctc.3c01053.
[121] Abd El Kawy M, Michel C, Kirollos F, El Kerdawy A, Sedeek M. In Vitro Mao-B Inhibitory Effect of Citrus Trifoliata L. Via Enzyme Assay and Molecular Docking Study. Egypt J Chem 2019;0:0–0. https://doi.org/10.21608/ejchem.2019.14735.1892.
[122] Negru PA, Bota SR, Stanasel OD, Blidar CF, Serban G. Molecular Docking Studies on Phenolic Constituents of Anethum graveolens L. Seed Extracts. J Pharm Res Int 2021:119–28. https://doi.org/10.9734/jpri/2021/v33i56B33939.
[123] Chen C-Y, Huang C-C, Tsai K-C, Huang W-J, Huang W-C, Hsu Y-C, et al. Evaluation of the Antihyperuricemic Activity of Phytochemicals from Davallia formosana by Enzyme Assay and Hyperuricemic Mice Model. Evid Based Complement Alternat Med 2014;2014:873607. https://doi.org/10.1155/2014/873607.
[124] Kumboonma P, Saenglee S, Senawong T, Phaosiri C. Histone Deacetylase Inhibitors and Antioxidants From the Root of Gluta usitata. Nat Prod Commun 2019;14:1934578X19895370. https://doi.org/10.1177/1934578X19895370.
[125] Naspiah N, Rizki Fadhil Pratama M, Sukardiman S S. Xanthine Oxidase Inhibition Activity and ADMET Properties of Terap (Artocarpus odoratissimus Blanco) Leaves Metabolites: Phytochemical Screening and in silico Studies. Pharmacogn J 2021;13:1150–60. https://doi.org/10.5530/pj.2021.13.148.
[126] Gallucci MN, Carezzano ME, Oliva MM, Demo MS, Pizzolitto RP, Zunino MP, et al. In vitro activity of natural phenolic compounds against fluconazole-resistant Candida species: a quantitative structure-activity relationship analysis. J Appl Microbiol 2014;116:795–804. https://doi.org/10.1111/jam.12432.
[127] Kolawole OA, Olatomide A F, Banjo S. Anti-gastric cancer activity of 1,2,3-triazolo[4,5-d]pyrimidine hybrids (1,2,3-TPH): QSAR and molecular docking approaches. Heliyon 2020;6:e03561. https://doi.org/10.1016/j.heliyon.2020.e03561.
[128] Wang Z, Zhu Y, Xu M, Peng K, Shi B, Wang Y, et al. Chrysanthemum as a remarkable edible flower resource with anti‐glycation effects: Representative variety differences, phenolic compositions, and the interaction mechanism. Food Front 2024;5:907–19. https://doi.org/10.1002/fft2.385.
[129] Ekowati J, Tejo BA, Maulana S, Kusuma WA, Fatriani R, Ramadhanti NS, et al. Potential Utilization of Phenolic Acid Compounds as Anti-Inflammatory Agents through TNF-α Convertase Inhibition Mechanisms: A Network Pharmacology, Docking, and Molecular Dynamics Approach. ACS Omega 2023;8:46851–68. https://doi.org/10.1021/acsomega.3c06450.
[130] Sedykh A, Fourches D, Duan J, Hucke O, Garneau M, Zhu H, et al. Human Intestinal Transporter Database: QSAR Modeling and Virtual Profiling of Drug Uptake, Efflux and Interactions. Pharm Res 2013;30:996–1007. https://doi.org/10.1007/s11095-012-0935-x.
[131] Zhao G, Zhang R, Dong L, Huang F, Liu L, Deng Y, et al. A Comparison of the Chemical Composition, In Vitro Bioaccessibility and Antioxidant Activity of Phenolic Compounds from Rice Bran and Its Dietary Fibres. Molecules 2018;23:202. https://doi.org/10.3390/molecules23010202.
[132] Tangney CC, Rasmussen HE. Polyphenols, Inflammation, and Cardiovascular Disease. Curr Atheroscler Rep 2013;15:324. https://doi.org/10.1007/s11883-013-0324-x.
[133] Kalita A, Das M, Das B, Baro MR. Molecular docking prediction and in vitro studies elucidate anti-inflammatory effect of Garcinia extract against inducible nitric oxide synthase and cyclooxygenase-2 targets. Beni-Suef Univ J Basic Appl Sci 2022;11:32. https://doi.org/10.1186/s43088-022-00214-2.
[134] Dral PO. AI in computational chemistry through the lens of a decade-long journey. Chem Commun 2024;60:3240–58. https://doi.org/10.1039/D4CC00010B.
[135] Zhang J, Chen D, Xia Y, Huang Y-P, Lin X, Han X, et al. Artificial Intelligence Enhanced Molecular Simulations. J Chem Theory Comput 2023;19:4338–50. https://doi.org/10.1021/acs.jctc.3c00214.
[136] Butler KT, Davies DW, Cartwright H, Isayev O, Walsh A. Machine learning for molecular and materials science. Nature 2018;559:547–55. https://doi.org/10.1038/s41586-018-0337-2.
[137] Chen JC, Kim AS. Brownian Dynamics, Molecular Dynamics, and Monte Carlo modeling of colloidal systems. Adv Colloid Interface Sci 2004;112:159–73. https://doi.org/10.1016/j.cis.2004.10.001.
[138] Salahshoori I, Mohseni A, Namayandeh Jorabchi M, Ghasemi S, Afshar M, Wohlrab S. Study of modified PVDF membranes with high-capacity adsorption features using Quantum mechanics, Monte Carlo, and Molecular Dynamics Simulations. J Mol Liq 2023;375:121286. https://doi.org/10.1016/j.molliq.2023.121286.
[139] Tiwary P, Herron L, John R, Lee S, Sanwal D, Wang R. Generative artificial intelligence for computational chemistry: a roadmap to predicting emergent phenomena 2024. https://doi.org/10.48550/ARXIV.2409.03118.
[140] Manzhos S, Carrington TJr. Neural Network Potential Energy Surfaces for Small Molecules and Reactions. Chem Rev 2021;121:10187–217. https://doi.org/10.1021/acs.chemrev.0c00665.
[141] Neha, Tiwari V, Mondal S, Kumari N, Karmakar T. Collective Variables for Crystallization Simulations─from Early Developments to Recent Advances. ACS Omega 2023;8:127–46. https://doi.org/10.1021/acsomega.2c06310.
[142] Rogal J. Reaction coordinates in complex systems-a perspective. Eur Phys J B 2021;94:223. https://doi.org/10.1140/epjb/s10051-021-00233-5.
[143] Bal KM, Fukuhara S, Shibuta Y, Neyts EC. Free energy barriers from biased molecular dynamics simulations. J Chem Phys 2020;153:114118. https://doi.org/10.1063/5.0020240.
[144] Ayres L, Benavidez T, Varillas A, Linton J, Whitehead DC, Garcia CD. Predicting Antioxidant Synergism via Artificial Intelligence and Benchtop Data. J Agric Food Chem 2023;71:15644–55. https://doi.org/10.1021/acs.jafc.3c05462.
[145] Bhaskar H, Hoyle DC, Singh S. Machine learning in bioinformatics: A brief survey and recommendations for practitioners. Comput Biol Med 2006;36:1104–25. https://doi.org/10.1016/j.compbiomed.2005.09.002.
[146] Nematzadeh S, Kiani F, Torkamanian-Afshar M, Aydin N. Tuning hyperparameters of machine learning algorithms and deep neural networks using metaheuristics: A bioinformatics study on biomedical and biological cases. Comput Biol Chem 2022;97:107619. https://doi.org/10.1016/j.compbiolchem.2021.107619.
[147] Zhang Y, Luo M, Wu P, Wu S, Lee T-Y, Bai C. Application of Computational Biology and Artificial Intelligence in Drug Design. Int J Mol Sci 2022;23:13568. https://doi.org/10.3390/ijms232113568.
[148] Hartley M, Iudin A, Padwardhan A, Sarkans U, Yoldaş AK, Kleywegt GJ. Providing open imaging data at scale: An EMBL-EBI perspective. Histochem Cell Biol 2023;160:211–21. https://doi.org/10.1007/s00418-023-02216-2.
[149] Eraslan G, Avsec Ž, Gagneur J, Theis FJ. Deep learning: new computational modelling techniques for genomics. Nat Rev Genet 2019;20:389–403.
[150] Taddese AA, Addis AC, Tam BT. Data stewardship and curation practices in AI-based genomics and automated microscopy image analysis for high-throughput screening studies: promoting robust and ethical AI applications. Hum Genomics 2025;19:16. https://doi.org/10.1186/s40246-025-00716-x.
[151] Houtgast EJ, Sima V-M, Bertels K, Al-Ars Z. Hardware acceleration of BWA-MEM genomic short read mapping for longer read lengths. Comput Biol Chem 2018;75:54–64.
[152] Hasan ME, Osman MA, Hemeida AA, ElHefnawi M. Bioinformatics and Artificial Intelligence Approaches in Metabolic Pathways. In: Soliman SSM, Husseiny MI, editors. Metab. Dyn. Host-Microbe Interact., Singapore: Springer Nature Singapore; 2025, p. 17–32. https://doi.org/10.1007/978-981-96-1305-2_2.
[153] Lu H, Xiao L, Liao W, Yan X, Nielsen J. Cell factory design with advanced metabolic modelling empowered by artificial intelligence. Metab Eng 2024.
[154] Song EZ. AI-enabled exploration of the “dark matter” of the protein universe. Theor Nat Sci 2024;59:86–93. https://doi.org/10.54254/2753-8818/59/20241365.
[155] Jumper J, Hassabis D. The Protein Structure Prediction Revolution and Its Implications for Medicine: 2023 Albert Lasker Basic Medical Research Award. JAMA 2023;330:1425. https://doi.org/10.1001/jama.2023.17095.
[156] Ren X, Li M, Zhang M, Zhao R, Han C. Invertase Plays a Vital Role in Regulating Wound-Induced Accumulation of Phenolic Compounds in Carrot Tissue. Horticulturae 2024;10:72. https://doi.org/10.3390/horticulturae10010072.
[157] Sarankar SK, Brajesh Rajak, Santosh Ojha, Sushma Somkuwar. Exploring the utilization of phenolic compounds in pharmaceuticals and healthcare. GSC Biol Pharm Sci 2023;24:095–102. https://doi.org/10.30574/gscbps.2023.24.3.0372.
[158] Kim S. Variable Autoencoders for Biosensor Data Augmentation 2021.
[159] Tatipamula VB, Kukavica B. Phenolic compounds as antidiabetic, anti‐inflammatory, and anticancer agents and improvement of their bioavailability by liposomes. Cell Biochem Funct 2021;39:926–44. https://doi.org/10.1002/cbf.3667.
[160] Borges A, De Freitas V, Mateus N, Fernandes I, Oliveira J. Solid Lipid Nanoparticles as Carriers of Natural Phenolic Compounds. Antioxidants 2020;9:998. https://doi.org/10.3390/antiox9100998.
[161] Idowu SO, Fatokun AA. Artificial Intelligence (AI) to the Rescue: Deploying Machine Learning to Bridge the Biorelevance Gap in Antioxidant Assays. SLAS Technol 2021;26:16–25. https://doi.org/10.1177/2472630320962716.
[162] Wang W, Shang H, Li J, Ma Y, Xu C, Ma J, et al. Four Different Structural Dietary Polyphenols, Especially Dihydromyricetin, Possess Superior Protective Effect on Ethanol-Induced ICE-6 and AML-12 Cytotoxicity: The Role of CYP2E1 and Keap1-Nrf2 Pathways. J Agric Food Chem 2023;71:1518–30. https://doi.org/10.1021/acs.jafc.2c06478.
[163] Damián-Medina K, Salinas-Moreno Y, Milenkovic D, Figueroa-Yáñez L, Marino-Marmolejo E, Higuera-Ciapara I, et al. In silico analysis of antidiabetic potential of phenolic compounds from blue corn (Zea mays L.) and black bean (Phaseolus vulgaris L.). Heliyon 2020;6:e03632. https://doi.org/10.1016/j.heliyon.2020.e03632.
[164] Euston S. Modelling of Protein–Polyphenol Interactions. 1st Int. E-Conf. Antioxid. Health Dis., MDPI; 2020, p. 22. https://doi.org/10.3390/CAHD2020-08893.
[165] Wróblewska B, Kuliga A, Wnorowska K. Bioactive Dairy-Fermented Products and Phenolic Compounds: Together or Apart. Molecules 2023;28:8081. https://doi.org/10.3390/molecules28248081.
[166] Wu Z, Chen J, Li Y, Deng Y, Zhao H, Hsieh C-Y, et al. From Black Boxes to Actionable Insights: A Perspective on Explainable Artificial Intelligence for Scientific Discovery. J Chem Inf Model 2023;63:7617–27. https://doi.org/10.1021/acs.jcim.3c01642.
[167] Fehr J, Citro B, Malpani R, Lippert C, Madai VI. A trustworthy AI reality-check: the lack of transparency of artificial intelligence products in healthcare. Front Digit Health 2024;6. https://doi.org/10.3389/fdgth.2024.1267290.
[168] Dwivedi R, Dave D, Naik H, Singhal S, Omer R, Patel P, et al. Explainable AI (XAI): Core Ideas, Techniques, and Solutions. ACM Comput Surv 2023;55:1–33. https://doi.org/10.1145/3561048.
[169] Xu F, Uszkoreit H, Du Y, Fan W, Zhao D, Zhu J. Explainable AI: A Brief Survey on History, Research Areas, Approaches and Challenges. In: Tang J, Kan M-Y, Zhao D, Li S, Zan H, editors. Nat. Lang. Process. Chin. Comput., vol. 11839, Cham: Springer International Publishing; 2019, p. 563–74. https://doi.org/10.1007/978-3-030-32236-6_51.
[170] Kalayil NV, D’Souza SS, Khan SY, Paul P. Artificial intelligence in pharmacy drug design. Artif Intell 2022;15.
[171] Raza MA, Aziz S, Noreen M, Saeed A, Anjum I, Ahmed M, et al. Artificial intelligence (AI) in pharmacy: an overview of innovations. Innov Pharm 2022;13:10–24926.
[172] Jacoba CMP, Celi LA, Silva PS. Biomarkers for Progression in Diabetic Retinopathy: Expanding Personalized Medicine through Integration of AI with Electronic Health Records. Semin Ophthalmol 2021;36:250–7. https://doi.org/10.1080/08820538.2021.1893351.
[173] Wasilewski T, Kamysz W, Gębicki J. AI-assisted detection of biomarkers by sensors and biosensors for early diagnosis and monitoring. Biosensors 2024;14:356.
[174] Vadapalli S, Abdelhalim H, Zeeshan S, Ahmed Z. Artificial intelligence and machine learning approaches using gene expression and variant data for personalized medicine. Brief Bioinform 2022;23:bbac191. https://doi.org/10.1093/bib/bbac191.
[175] Sherani AMK, Khan M, Qayyum MU, Hussain HK. Synergizing AI and Healthcare: Pioneering Advances in Cancer Medicine for Personalized Treatment. Int J Multidiscip Sci Arts 2024;3:270–7. https://doi.org/10.47709/ijmdsa.v3i01.3562.
[176] Varghese R, Shringi H, Efferth T, Ramamoorthy S. Artificial intelligence driven approaches in phytochemical research: trends and prospects. Phytochem Rev 2025. https://doi.org/10.1007/s11101-025-10096-8.
[177] Machitescu AMD, Stanga CM, Stanila A, Diaconeasa ZM. Emerging technologies in polyphenol analysis: from traditional methods to -omics approaches. Hop Med Plants 2024;32:56–101. https://doi.org/10.15835/hpm.v32i1-2.15019.
[178] Chan HCS, Shan H, Dahoun T, Vogel H, Yuan S. Advancing Drug Discovery via Artificial Intelligence. Trends Pharmacol Sci 2019;40:592–604. https://doi.org/10.1016/j.tips.2019.06.004.
[179] Ding H, Tian J, Yu W, Wilson DI, Young BR, Cui X, et al. The Application of Artificial Intelligence and Big Data in the Food Industry. Foods 2023;12:4511. https://doi.org/10.3390/foods12244511.
[180] Versini R, Sritharan S, Aykac Fas B, Tubiana T, Aimeur SZ, Henri J, et al. A Perspective on the Prospective Use of AI in Protein Structure Prediction. J Chem Inf Model 2024;64:26–41. https://doi.org/10.1021/acs.jcim.3c01361.
[181] García-Vera YS, Juca-Maldonado FX, Torres-Gallegos V. Automatización de procesos contables mediante Inteligencia Artificial: Oportunidades y desafíos para pequeños empresarios ecuatorianos. Rev Transdiciplinaria Estud Soc Tecnológicos 2023;3:68–74.
[182] Michel JG. Could Machines Replace Human Scientists?: Digitalization and Scientific Discoveries. Artif. Intell., Brill mentis; 2020, p. 361–76.
[183] Thomas A, Kuppasani PR. Advantages and Disadvantages of Artificial Intelligence. Artif. Intell. Biol. Sci., CRC Press; 2025, p. 93–110.
[184] Usher M, Barak M. Unpacking the role of AI ethics online education for science and engineering students. Int J STEM Educ 2024;11:35. https://doi.org/10.1186/s40594-024-00493-4.
[185] Obregón Domínguez JA. Beneficio de redes neuronales en el modelamiento de la optimización del pre-tratamiento osmótico en mermelada de arándano (vaccinium corymbosum l.) variedad biloxi 2018.
[186] López-Valdez LG, Martínez-Blanco G, Zuleta-Prada H. Análisis QSAR con Machine Learning de una biblioteca virtual de derivados del O-etil-glucósido de semillas de randia aculeata. Mem Mesa 4 Quím 2021:127.
[187] Hansch C, McKarns SC, Smith CJ, Doolittle DJ. Comparative QSAR evidence for a free-radical mechanism of phenol-induced toxicity. Chem Biol Interact 2000;127:61–72.
[188] Bian Y, Xie X-Q. Generative chemistry: drug discovery with deep learning generative models. J Mol Model 2021;27:71. https://doi.org/10.1007/s00894-021-04674-8.
[189] Cui Z, Qi C, Zhou T, Yu Y, Wang Y, Zhang Z, et al. Artificial intelligence and food flavor: How AI models are shaping the future and revolutionary technologies for flavor food development. Compr Rev Food Sci Food Saf 2025;24:e70068. https://doi.org/10.1111/1541-4337.70068.
[190] García-Jiménez B, Muñoz J, Cabello S, Medina J, Wilkinson MD. Predicting microbiomes through a deep latent space. Bioinformatics 2021;37:1444–51.
[191] Hameed K, Chai D, Rassau A. Texture-based latent space disentanglement for enhancement of a training dataset for ANN-based classification of fruit and vegetables. Inf Process Agric 2023;10:85–105.
[192] Esfanjani AF, Jafari SM. Biopolymer nano-particles and natural nano-carriers for nano-encapsulation of phenolic compounds. Colloids Surf B Biointerfaces 2016;146:532–43.
[193] Macías-Cortés E, Gallegos-Infante JA, Rocha-Guzmán NE, Moreno-Jiménez MR, Medina-Torres L, González-Laredo RF. Microencapsulation of phenolic compounds: Technologies and novel polymers. Rev Mex Ing Quím 2020;19:491–521.
[194] Hu Q, Luo Y. Chitosan-based nanocarriers for encapsulation and delivery of curcumin: A review. Int J Biol Macromol 2021;179:125–35. https://doi.org/10.1016/j.ijbiomac.2021.02.216.
[195] Abdel-Aty AM, Gad AAM, Barakat AZ, Mohamed SA. Microencapsulation of Antioxidant Phenolics from Tamarind Seed Peels Using Chia Gum and Maltodextrin. Sci Rep 2025;15:6720. https://doi.org/10.1038/s41598-025-89792-6.
[196] Serini S, Trombino S, Curcio F, Sole R, Cassano R, Calviello G. Hyaluronic Acid-Mediated Phenolic Compound Nanodelivery for Cancer Therapy. Pharmaceutics 2023;15:1751. https://doi.org/10.3390/pharmaceutics15061751.
[197] Costa C, Anselmo H, Ferro R, Matos AS, Casimiro T, Aguiar-Ricardo A. Dry Dosage Forms of Add-Value Bioactive Phenolic Compounds by Supercritical CO2-Assisted Spray-Drying. Molecules 2022;27:2001. https://doi.org/10.3390/molecules27062001.
[198] Azkia MN, Setyaningsih W, Mayangsari Y, Cahyanto MN. Enhancement in Bioaccessibility and Bioavailability of Phenolic Compounds during Black Glutinous Rice Tape Fermentation. agriTECH 2024;44:362. https://doi.org/10.22146/agritech.92729.
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Derechos de autor 2025 Mario Iván Cruz-Ávila, Jesús Guadalupe Pérez Flores, Laura García-Curiel, Emmanuel Pérez-Escalante, Judith Jaimez-Ordaz, Elizabeth Contreras-López
Esta obra está bajo una licencia internacional Creative Commons Atribución-NoComercial-SinDerivadas 4.0.
