{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T21:03:27Z","timestamp":1790283807561,"version":"4.1.0"},"reference-count":62,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,27]],"date-time":"2025-12-27T00:00:00Z","timestamp":1766793600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The optimization of bioactive compound extraction from medicinal herbs is critical for developing functional food ingredients with substantiated health benefits. This study employed response surface methodology (RSM) and partial least squares (PLS) regression to maximize polyphenol recovery and antioxidant capacity from five medicinal herbs (Helichrysum stoechas, Chelidonium majus, Mentha pulegium, Artemisia absinthium, and Adiantum capillus-veneris). A custom experimental design assessed the effects of herb identity, extraction technique, and solvent-to-solid ratio on total polyphenolic content (TPC), total flavonoid content (TFC), ferric reducing antioxidant power (FRAP), and DPPH radical scavenging activity. The PLS compromise optimum was identified for M. pulegium using 60% ethanol at 55 mL\/g, yielding 37.54 \u00b1 2.10 mg GAE\/g dw TPC, 21.62 \u00b1 1.15 mg RtE\/g dw TFC, 334.38 \u00b1 12.37 \u00b5mol AAE\/g dw FRAP, and 262.67 \u00b1 9.46 \u00b5mol AAE\/g dw DPPH. HPLC-DAD profiling revealed 18 polyphenolic compounds (10.22 \u00b1 0.34 mg\/g dw), dominated by kaempferol-3-O-\u03b2-rutinoside, protocatechuic acid, and luteolin-7-O-glucoside. These compounds contribute complementary mechanisms: protocatechuic acid modulates oxidative and antioxidant pathways, kaempferol-3-O-\u03b2-rutinoside exerts cardioprotective and anti-inflammatory effects via VEGF-C binding, and luteolin-7-O-glucoside suppresses NF-\u03baB-mediated inflammatory signaling. Principal component analysis (PCA) explained 84.8% of variance, clearly separating optimized from non-optimized extracts, while PLS confirmed strong correlations between specific phenolics and antioxidant indices. Overall, this integrated chemometric approach demonstrates that data-driven optimization can deliver phenolic-rich herbal extracts with robust and balanced antioxidant potential for functional food applications.<\/jats:p>","DOI":"10.3390\/ijms27010309","type":"journal-article","created":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T05:28:19Z","timestamp":1766986099000},"page":"309","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Data-Driven Optimization of Polyphenol Recovery and Antioxidant Capacity from Medicinal Herbs Using Chemometrics and HPLC Profiling for Functional Food Applications"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8707-8809","authenticated-orcid":false,"given":"Vassilis","family":"Athanasiadis","sequence":"first","affiliation":[{"name":"Department of Food Science & Nutrition, University of Thessaly, Terma N. Temponera Str., 43100 Karditsa, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erva","family":"Avdoulach-Chatzi-Giousouf","sequence":"additional","affiliation":[{"name":"Department of Food Science & Nutrition, University of Thessaly, Terma N. Temponera Str., 43100 Karditsa, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Errika","family":"Koulouri","sequence":"additional","affiliation":[{"name":"Department of Food Science & Nutrition, University of Thessaly, Terma N. Temponera Str., 43100 Karditsa, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8751-2468","authenticated-orcid":false,"given":"Dimitrios","family":"Kalompatsios","sequence":"additional","affiliation":[{"name":"Department of Food Science & Nutrition, University of Thessaly, Terma N. Temponera Str., 43100 Karditsa, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6825-7350","authenticated-orcid":false,"given":"Stavros I.","family":"Lalas","sequence":"additional","affiliation":[{"name":"Department of Food Science & Nutrition, University of Thessaly, Terma N. Temponera Str., 43100 Karditsa, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"R158","DOI":"10.1016\/j.cub.2023.12.038","article-title":"Medicinal plants meet modern biodiversity science","volume":"34","author":"Davis","year":"2024","journal-title":"Curr. Biol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Sun, W., and Shahrajabian, M.H. (2023). Therapeutic Potential of Phenolic Compounds in Medicinal Plants\u2014Natural Health Products for Human Health. Molecules, 28.","DOI":"10.3390\/molecules28041845"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Rudrapal, M., Khairnar, S.J., Khan, J., Dukhyil, A.B., Ansari, M.A., Alomary, M.N., Alshabrmi, F.M., Palai, S., Deb, P.K., and Devi, R. (2022). Dietary Polyphenols and Their Role in Oxidative Stress-Induced Human Diseases: Insights Into Protective Effects, Antioxidant Potentials and Mechanism(s) of Action. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.806470"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Hbika, A., Elbouzidi, A., Taibi, M., Ouahabi, S., Loukili, E.H., Bouyanzer, A., Yahyaoui, M.I., Asehraou, A., El Hachlafi, N., and Salamatullah, A.M. (2024). Isolation of Arborescin from Artemisia absinthium L. and Study of Its Antioxidant and Antimicrobial Potential by Use of In Vitro and In Silico Approaches. Separations, 11.","DOI":"10.3390\/separations11070209"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Batiha, G.E.-S., Olatunde, A., El-Mleeh, A., Hetta, H.F., Al-Rejaie, S., Alghamdi, S., Zahoor, M., Magdy Beshbishy, A., Murata, T., and Zaragoza-Bastida, A. (2020). Bioactive Compounds, Pharmacological Actions, and Pharmacokinetics of Wormwood (Artemisia absinthium). Antibiotics, 9.","DOI":"10.3390\/antibiotics9060353"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Szopa, A., Pajor, J., Klin, P., Rzepiela, A., Elansary, H.O., Al-Mana, F.A., Mattar, M.A., and Ekiert, H. (2020). Artemisia absinthium L.\u2014Importance in the History of Medicine, the Latest Advances in Phytochemistry and Therapeutical, Cosmetological and Culinary Uses. Plants, 9.","DOI":"10.3390\/plants9091063"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Liu, Z., Li, X., Jin, Y., Nan, T., Zhao, Y., Huang, L., and Yuan, Y. (2023). New Evidence for Artemisia absinthium as an Alternative to Classical Antibiotics: Chemical Analysis of Phenolic Compounds, Screening for Antimicrobial Activity. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241512044"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1016\/j.indcrop.2014.01.004","article-title":"Exploring the antioxidant potential of Helichrysum stoechas (L.) Moench phenolic compounds for cosmetic applications: Chemical characterization, microencapsulation and incorporation into a moisturizer","volume":"53","author":"Barroso","year":"2014","journal-title":"Ind. Crops Prod."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"101826","DOI":"10.1016\/j.bcab.2020.101826","article-title":"Phytochemical analysis, antioxidant and anti-inflammatory activities of Helichrysum stoechas (L.) Moench extracts","volume":"29","author":"Kherbache","year":"2020","journal-title":"Biocatal. Agric. Biotechnol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"112483","DOI":"10.1016\/j.fct.2021.112483","article-title":"Comparative analysis of metabolic variations, antioxidant potential and cytotoxic effects in different parts of Chelidonium majus L.","volume":"156","author":"Nile","year":"2021","journal-title":"Food Chem. Toxicol."},{"key":"ref_11","first-page":"260","article-title":"Seasonal variability of Chelidonium majus L. secondary metabolites content and antioxidant activity","volume":"12","author":"Jakovljevic","year":"2013","journal-title":"EXCLI J."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Borges, A., Ord\u00f3\u00f1ez-D\u00edaz, J.L., Aquino, Y., Moreno-Rojas, J.M., Calvo, M.L.M., Vaz, J.A., and Calhelha, R.C. (2025). Analysis of the Phenolic Profile of Chelidonium majus L. and Its Combination with Sericin: Balancing Antimicrobial Activity and Cytocompatibility. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26209911"},{"key":"ref_13","first-page":"188","article-title":"Medicinal Properties of Adiantum capillus-veneris Linn. in Traditional Medicine and Modern Phytotherapy: A Review Article","volume":"47","author":"Dehdari","year":"2018","journal-title":"Iran. J. Public Health"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"186","DOI":"10.2174\/1570163817666200316111445","article-title":"A Review of Pharmacological Properties and Toxicological Effects of Adiantum capillus-veneris L.","volume":"18","author":"Kashkooe","year":"2021","journal-title":"Curr. Drug Discov. Technol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e71118","DOI":"10.1002\/fsn3.71118","article-title":"Adiantum capillus-veneris: A Comprehensive Review of Its Medicinal Properties, Bioactive Compounds, and Advanced Extraction Techniques","volume":"13","author":"Qadir","year":"2025","journal-title":"Food Sci. Nutr."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"302","DOI":"10.2174\/1871530323666230914103731","article-title":"Mentha Pulegium: A Plant with Several Medicinal Properties","volume":"24","author":"Amtaghri","year":"2024","journal-title":"Endocr. Metab. Immune Disord. Drug Targets"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Al-Rajhi, A.M.H., Qanash, H., Almuhayawi, M.S., Al Jaouni, S.K., Bakri, M.M., Ganash, M., Salama, H.M., Selim, S., and Abdelghany, T.M. (2022). Molecular Interaction Studies and Phytochemical Characterization of Mentha pulegium L. Constituents with Multiple Biological Utilities as Antioxidant, Antimicrobial, Anticancer and Anti-Hemolytic Agents. Molecules, 27.","DOI":"10.3390\/molecules27154824"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Wojtunik-Kulesza, K.A. (2022). Toxicity of Selected Monoterpenes and Essential Oils Rich in These Compounds. Molecules, 27.","DOI":"10.3390\/molecules27051716"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Brzezi\u0144ska, R., G\u00f3rska, A., Wirkowska-Wojdy\u0142a, M., and Piasecka, I. (2023). Response Surface Methodology as a Tool for Optimization of Extraction Process of Bioactive Compounds from Spent Coffee Grounds. Appl. Sci., 13.","DOI":"10.3390\/app13137634"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Zg\u00f3rka, G., Adamska-Szewczyk, A., and Baj, T. (2023). Response Surface Methodology in Optimising the Extraction of Polyphenolic Antioxidants from Flower Buds of Magnolia \u00d7 soulangeana Soul.-Bod. var. \u2018Lennei\u2019 and Their Detailed Qualitative and Quantitative Profiling. Molecules, 28.","DOI":"10.3390\/molecules28176335"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Tsanaktsidou, E., Karavasili, C., Zacharis, C.K., Fatouros, D.G., and Markopoulou, C.K. (2020). Partial Least Square Model (PLS) as a Tool to Predict the Diffusion of Steroids Across Artificial Membranes. Molecules, 25.","DOI":"10.3390\/molecules25061387"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Liu, Y., Dar, B.N., Makroo, H.A., Aslam, R., Mart\u00ed-Quijal, F.J., Castagnini, J.M., Amigo, J.M., and Barba, F.J. (2024). Optimizing Recovery of High-Added-Value Compounds from Complex Food Matrices Using Multivariate Methods. Antioxidants, 13.","DOI":"10.3390\/antiox13121510"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"131918","DOI":"10.1016\/j.foodchem.2021.131918","article-title":"Influence of the extraction method on the recovery of bioactive phenolic compounds from food industry by-products","volume":"378","author":"Romero","year":"2022","journal-title":"Food Chem."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Messaoudi, M., Rebiai, A., Sawicka, B., Atanassova, M., Ouakouak, H., Larkem, I., Egbuna, C., Awuchi, C.G., Boubekeur, S., and Ferhat, M.A. (2022). Effect of Extraction Methods on Polyphenols, Flavonoids, Mineral Elements, and Biological Activities of Essential Oil and Extracts of Mentha pulegium L.. Molecules, 27.","DOI":"10.3390\/molecules27010011"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Balciunaitiene, A., Viskelis, P., Viskelis, J., Streimikyte, P., Liaudanskas, M., Bartkiene, E., Zavistanaviciute, P., Zokaityte, E., Starkute, V., and Ruzauskas, M. (2021). Green Synthesis of Silver Nanoparticles Using Extract of Artemisia absinthium L., Humulus lupulus L. and Thymus vulgaris L., Physico-Chemical Characterization, Antimicrobial and Antioxidant Activity. Processes, 9.","DOI":"10.3390\/pr9081304"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Samanidis, I., Krigas, N., Athanasiadis, V., Makrygiannis, I., Mantiniotou, M., and Lalas, S.I. (2025). A Comparative Phytochemical Investigation of the Greek Members of the Genus Helichrysum Mill., with Emphasis on the Local Endemic Helichrysum amorginum Boiss and Orph. Plants, 14.","DOI":"10.3390\/plants14020229"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Brka, M., Omanovi\u0107-Mikli\u010danin, E., Grahi\u0107, J., Muhamedagi\u0107, S., Muj\u010dinovi\u0107, A., Toroman, A., and Falan, V. (2023). Antioxidant Activity and Total Phenolic Content Determining in Samples of Celandine (Chelidonium majus L.) by Applying Different Solvents. Proceedings of the 32nd Scientific-Expert Conference of Agriculture and Food Industry, Springer Nature.","DOI":"10.1007\/978-3-031-47467-5"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Seif, M., Aati, H., Amer, M., Ragauskas, A.J., Seif, A., El-Sappah, A.H., Aati, A., Madboli, A.E.-N.A., and Emam, M. (2023). Mitigation of Hepatotoxicity via Boosting Antioxidants and Reducing Oxidative Stress and Inflammation in Carbendazim-Treated Rats Using Adiantum capillus-veneris L. Extract. Molecules, 28.","DOI":"10.3390\/molecules28124720"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"125771","DOI":"10.1016\/j.talanta.2024.125771","article-title":"A comprehensive and critical review of the unstandardized Folin-Ciocalteu assay to determine the total content of polyphenols: The conundrum of the experimental factors and method validation","volume":"272","author":"Raposo","year":"2024","journal-title":"Talanta"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Lawag, I.L., Nolden, E.S., Schaper, A.A.M., Lim, L.Y., and Locher, C. (2023). A Modified Folin-Ciocalteu Assay for the Determination of Total Phenolics Content in Honey. Appl. Sci., 13.","DOI":"10.3390\/app13042135"},{"key":"ref_31","first-page":"570","article-title":"Investigation of antioxidant activities and phenolic profiles of the methanol extracts of Rumex acetosella, Mentha pulegium, Piper cubeba, and Elettaria cardamomum","volume":"159","author":"Inan","year":"2025","journal-title":"Plant Biosyst. Int. J. Deal. Asp. Plant Biol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1016\/j.sajb.2021.10.024","article-title":"Phenolic Profile, Antioxidant and Enzyme Inhibitory Properties of Phenolic-Rich Fractions from the Aerial Parts of Mentha pulegium L.","volume":"146","author":"Abbou","year":"2022","journal-title":"S. Afr. J. Bot."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1016\/j.sajb.2022.08.001","article-title":"HPLC-DAD and HPLC-ESI-MS-MS profiles of hydroalcoholic extracts of Chamaemelum nobile and Mentha pulegium, and study of their antihemolytic activity against AAPH-induced hemolysis","volume":"150","author":"Tacherfiout","year":"2022","journal-title":"S. Afr. J. Bot."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"EFSA Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids (CEF), Silano, V., Bolognesi, C., Castle, L., Cravedi, J.-P., Engel, K.-H., Fowler, P., Franz, R., Grob, K., and G\u00fcrtler, R. (2017). Scientific Opinion on Flavouring Group Evaluation 57, Revision 1 (FGE.57Rev1): Consideration of isopulegone and three flavouring substances evaluated by JECFA (55th meeting). EFSA J., 15, e04727.","DOI":"10.2903\/j.efsa.2017.4727"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Cadena-I\u00f1iguez, J., Santiago-Osorio, E., S\u00e1nchez-Flores, N., Salazar-Aguilar, S., Soto-Hern\u00e1ndez, R.M., Riviello-Flores, M.d.l.L., Mac\u00edas-Zaragoza, V.M., and Agui\u00f1iga-S\u00e1nchez, I. (2024). The Cancer-Protective Potential of Protocatechuic Acid: A Narrative Review. Molecules, 29.","DOI":"10.3390\/molecules29071439"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"6339","DOI":"10.1021\/acs.jafc.3c09033","article-title":"Improving the Effects of Mulberry Leaves and Neochlorogenic Acid on Glucotoxicity-Induced Hepatic Steatosis in High Fat Diet Treated db\/db Mice","volume":"72","author":"Tsai","year":"2024","journal-title":"J. Agric. Food Chem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"154961","DOI":"10.1016\/j.phymed.2023.154961","article-title":"Chlorogenic acids: A pharmacological systematic review on their hepatoprotective effects","volume":"118","author":"Xue","year":"2023","journal-title":"Phytomedicine"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"31396","DOI":"10.1038\/s41598-025-13965-6","article-title":"Spectroscopic, antioxidant and cytotoxicity studies of vanillic acids","volume":"15","author":"Swislocka","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"111760","DOI":"10.1016\/j.foodres.2022.111760","article-title":"Effect of caffeic acid esters on antioxidant activity and oxidative stability of sunflower oil: Molecular simulation and experiments","volume":"160","author":"Lu","year":"2022","journal-title":"Food Res. Int."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Zhao, Z., Yang, Q., Sun, Y., and Ruan, X. (2025). Unveiling the antioxidant and anti-inflammatory potential of syringic acid: Mechanistic insights and pathway interactions. Front. Pharmacol., 16.","DOI":"10.3389\/fphar.2025.1615294"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1134\/S181971242302023X","article-title":"Kaempferol-3-O-Rutinoside: A Natural Flavonoid Glycosides with Multifaceted Therapeutic Potential","volume":"17","author":"Zhou","year":"2023","journal-title":"Neurochem. J."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"112580","DOI":"10.1016\/j.postharvbio.2023.112580","article-title":"Ultraviolet B-induced increase of cyanidin-3-O-galactoside, quercetin-3-O-galactoside, and ursolic acid enhances antioxidant and anti-inflammatory activities in apples","volume":"206","author":"Lim","year":"2023","journal-title":"Postharvest Biol. Technol."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"De Stefano, A., Caporali, S., Di Daniele, N., Rovella, V., Cardillo, C., Schinzari, F., Minieri, M., Pieri, M., Candi, E., and Bernardini, S. (2021). Anti-Inflammatory and Proliferative Properties of Luteolin-7-O-Glucoside. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22031321"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Nile, A., Nile, S.H., Shin, J., Park, G., and Oh, J.-W. (2021). Quercetin-3-Glucoside Extracted from Apple Pomace Induces Cell Cycle Arrest and Apoptosis by Increasing Intracellular ROS Levels. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms221910749"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"139459","DOI":"10.1016\/j.foodchem.2024.139459","article-title":"Antioxidant activity of the main phenolics found in red fruits: An in vitro and in silico study","volume":"452","author":"Alves","year":"2024","journal-title":"Food Chem."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Caporali, S., De Stefano, A., Calabrese, C., Giovannelli, A., Pieri, M., Savini, I., Tesauro, M., Bernardini, S., Minieri, M., and Terrinoni, A. (2022). Anti-Inflammatory and Active Biological Properties of the Plant-Derived Bioactive Compounds Luteolin and Luteolin 7-Glucoside. Nutrients, 14.","DOI":"10.3390\/nu14061155"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Felice, M.R., Maugeri, A., De Sarro, G., Navarra, M., and Barreca, D. (2022). Molecular Pathways Involved in the Anti-Cancer Activity of Flavonols: A Focus on Myricetin and Kaempferol. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23084411"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Kowalczyk, A., Tuberoso, C.I.G., and Jerkovi\u0107, I. (2024). The Role of Rosmarinic Acid in Cancer Prevention and Therapy: Mechanisms of Antioxidant and Anticancer Activity. Antioxidants, 13.","DOI":"10.3390\/antiox13111313"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Maugeri, A., Calderaro, A., Patan\u00e8, G.T., Navarra, M., Barreca, D., Cirmi, S., and Felice, M.R. (2023). Targets Involved in the Anti-Cancer Activity of Quercetin in Breast, Colorectal and Liver Neoplasms. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24032952"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Zafar, A., Alruwaili, N.K., Imam, S.S., Alsaidan, O.A., Ahmed, M.M., Yasir, M., Warsi, M.H., Alquraini, A., Ghoneim, M.M., and Alshehri, S. (2022). Development and Optimization of Hybrid Polymeric Nanoparticles of Apigenin: Physicochemical Characterization, Antioxidant Activity and Cytotoxicity Evaluation. Sensors, 22.","DOI":"10.3390\/s22041364"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Zhang, Q., Pan, J., Liu, H., and Jiao, Z. (2023). Characterization of the Synergistic Antioxidant Activity of Epigallocatechin Gallate (EGCG) and Kaempferol. Molecules, 28.","DOI":"10.3390\/molecules28135265"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Bellumori, M., Innocenti, M., Congiu, F., Cencetti, G., Raio, A., Menicucci, F., Mulinacci, N., and Michelozzi, M. (2021). Within-Plant Variation in Rosmarinus officinalis L. Terpenes and Phenols and Their Antimicrobial Activity against the Rosemary Phytopathogens Alternaria alternata and Pseudomonas viridiflava. Molecules, 26.","DOI":"10.3390\/molecules26113425"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1713","DOI":"10.1016\/j.toxrep.2022.09.001","article-title":"Molecular mechanisms associated with the chemoprotective role of protocatechuic acid and its potential benefits in the amelioration of doxorubicin-induced cardiotoxicity: A review","volume":"9","author":"Okpara","year":"2022","journal-title":"Toxicol. Rep."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Tayeh, Z., and Ofir, R. (2018). Asteriscus graveolens Extract in Combination with Cisplatin\/Etoposide\/Doxorubicin Suppresses Lymphoma Cell Growth through Induction of Caspase-3 Dependent Apoptosis. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19082219"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1432","DOI":"10.1016\/j.joule.2021.04.012","article-title":"Selective hydrogen peroxide conversion tailored by surface, interface, and device engineering","volume":"5","author":"Tang","year":"2021","journal-title":"Joule"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1093\/cvr\/cvz163","article-title":"Levosimendan prevents doxorubicin-induced cardiotoxicity in time- and dose-dependent manner: Implications for inotropy","volume":"116","author":"Efentakis","year":"2020","journal-title":"Cardiovasc. Res."},{"key":"ref_57","first-page":"00177","article-title":"Protocatecheuic Acid Underlies the Antioxidant Activity Exhibited by Illicium Verum Fruit","volume":"6","author":"Bhatti","year":"2017","journal-title":"J. Anal. Pharm. Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.ejphar.2019.01.033","article-title":"Dietary protocatechuic acid abrogates male reproductive dysfunction in streptozotocin-induced diabetic rats via suppression of oxidative damage, inflammation and caspase-3 activity","volume":"849","author":"Adedara","year":"2019","journal-title":"Eur. J. Pharmacol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"153400","DOI":"10.1016\/j.phymed.2020.153400","article-title":"The binding of kaempferol-3-O-rutinoside to vascular endothelial growth factor potentiates anti-inflammatory efficiencies in lipopolysaccharide-treated mouse macrophage RAW264.7 cells","volume":"80","author":"Hu","year":"2021","journal-title":"Phytomedicine"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Kalompatsios, D., Athanasiadis, V., Mantiniotou, M., and Lalas, S.I. (2024). Optimization of Ultrasonication Probe-Assisted Extraction Parameters for Bioactive Compounds from Opuntia macrorhiza Using Taguchi Design and Assessment of Antioxidant Properties. Appl. Sci., 14.","DOI":"10.3390\/app142210460"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Mantiniotou, M., Athanasiadis, V., Kalompatsios, D., Bozinou, E., Ntourtoglou, G., Dourtoglou, V.G., and Lalas, S.I. (2025). Atmospheric Room Temperature Plasma as a Green Pretreatment Strategy for Enhanced Phytochemical Extraction from Moringa oleifera Leaves. Foods, 14.","DOI":"10.3390\/foods14183233"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Togantzi, M.-I., Mantiniotou, M., Kalompatsios, D., Athanasiadis, V., Giovanoudis, I., and Lalas, S.I. (2025). Cloud Point Extraction as a Green Method for the Extraction of Antioxidant Compounds from the Juice of Second-Grade Apples. Biomass, 5.","DOI":"10.3390\/biomass5030048"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/1\/309\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,30]],"date-time":"2025-12-30T05:17:01Z","timestamp":1767071821000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/1\/309"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,27]]},"references-count":62,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,1]]}},"alternative-id":["ijms27010309"],"URL":"https:\/\/doi.org\/10.3390\/ijms27010309","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,27]]}}}