{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T22:28:48Z","timestamp":1791584928466,"version":"4.3.4"},"reference-count":49,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,3,18]],"date-time":"2025-03-18T00:00:00Z","timestamp":1742256000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Program for Research of the National Association of Technical Universities","award":["4\/06.10.2023"],"award-info":[{"award-number":["4\/06.10.2023"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Hawthorns (Crataegus monogyna L.) contain numerous bioactive compounds, with its extracts demonstrating health benefits. This study focused on optimizing a more sustainable extraction method, specifically microwave-assisted extraction (MAE), to obtain polyphenols from hawthorn leaves and flowers. HPLC\/UV analysis identified key compounds, including gallic and chlorogenic acids, isoquercetin, rutin, hyperoside, vitexin, and quercetin. Principal component analysis (PCA) assessed correlations between extraction conditions, total phenolic content (TPC), and key compounds. PCA grouped conditions into three clusters, with two remaining ungrouped. The highest vitexin, rutin, and isoquercetin contents were achieved at 60 \u00b0C for 10 min using 160\u2013500 \u03bcm particles in 75% ethanol (20\/1 ratio) or 50% ethanol (20\/1 and 30\/1 ratios). An ungrouped condition (60 \u00b0C, 10 min, &lt; 160 \u03bcm particles, 50% ethanol, 20\/1 ratio) produced a higher TPC and greater gallic acid, chlorogenic acid, and hyperoside concentrations. The TPC and antioxidant activity (AA) of the extracts were optimized using a 23 full factorial design, with temperature, ethanol concentration, and solvent-to-plant ratio as variables. Optimal MAE conditions (S\/Popt = 20.4 mL\/g, Topt = 65 \u00b0C, and EtOHopt = 60%) yielded a TPC of 116.23 \u00b1 2.85 mg GAE\/g DM and an AA of 237.6 \u00b1 6.33 mg TE\/g DM using hawthorn leaves and flowers. Summarizing the above, to maximize phytocompound content, a one-factor-at-a-time design identified extraction parameters, but its limitations led to a 23 full factorial design. The latter effectively optimized the TPC and AA, while PCA revealed correlations between extraction parameters, total phenolics, and key compounds.<\/jats:p>","DOI":"10.3390\/antiox14030357","type":"journal-article","created":{"date-parts":[[2025,3,18]],"date-time":"2025-03-18T10:43:51Z","timestamp":1742294631000},"page":"357","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Optimization of Microwave-Assisted Extraction of Polyphenols from Crataegus monogyna L."],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0369-594X","authenticated-orcid":false,"given":"Adina I.","family":"Gavrila","sequence":"first","affiliation":[{"name":"Faculty of Chemical Engineering and Biotechnologies, National University of Science and Technology Politehnica Bucharest, 011061 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilia J.","family":"Damian","sequence":"additional","affiliation":[{"name":"Research & Development Department, Teva Pharmaceuticals S.R.L., 011171 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anca","family":"Rosca","sequence":"additional","affiliation":[{"name":"Faculty of Chemical Engineering and Biotechnologies, National University of Science and Technology Politehnica Bucharest, 011061 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4141-6697","authenticated-orcid":false,"given":"Ioan","family":"Calinescu","sequence":"additional","affiliation":[{"name":"Faculty of Chemical Engineering and Biotechnologies, National University of Science and Technology Politehnica Bucharest, 011061 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camelia","family":"Hodosan","sequence":"additional","affiliation":[{"name":"Faculty of Engineering and Animal Production, University of Agronomic Sciences and Veterinary Medicine, 011464 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6190-1548","authenticated-orcid":false,"given":"Ioana","family":"Popa","sequence":"additional","affiliation":[{"name":"Faculty of Chemical Engineering and Biotechnologies, National University of Science and Technology Politehnica Bucharest, 011061 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Arias-S\u00e1nchez, R.A., Torner, L., and Navarro, B.F. (2023). Polyphenols and neurodegenerative diseases: Potential effects and mechanisms of neuroprotection. Molecules, 28.","DOI":"10.3390\/molecules28145415"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1007\/s11064-008-9808-4","article-title":"Oxidative damage and cognitive dysfunction: Antioxidant treatments to promote healthy brain aging","volume":"34","author":"Head","year":"2009","journal-title":"Neurochem. Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"325","DOI":"10.5607\/en.2015.24.4.325","article-title":"The role of oxidative stress in neurodegenerative diseases","volume":"24","author":"Kim","year":"2015","journal-title":"Exp. Neurobiol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Rojas-Garcia, A., Fernandez-Ochoa, A., Cadiz-Gurrea, M.L., Arraez-Roman, D., and Segura-Carretero, A. (2023). Neuroprotective effects of agri-food by-products rich in phenolic compounds. Nutrients, 15.","DOI":"10.3390\/nu15020449"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1016\/j.freeradbiomed.2003.11.023","article-title":"Flavonoid permeability across an in situ model of the blood-brain barrier","volume":"36","author":"Youdim","year":"2004","journal-title":"Free Radic Biol. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.colcom.2016.06.002","article-title":"Biomimetic polyphenol coatings for antioxidant active packaging applications","volume":"13","author":"Roman","year":"2016","journal-title":"Colloid Interface Sci. Commun."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/j.bioorg.2018.10.051","article-title":"Rhamnocitrin isolated from Prunus padus var. seoulensis: A potent and selective reversible inhibitor of human monoamine oxidase A","volume":"83","author":"Baek","year":"2019","journal-title":"Bioorganic Chem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1097\/WNR.0000000000000358","article-title":"Methyl 3,4-dihydroxybenzoate promote rat cortical neurons survival and neurite outgrowth through the adenosine A2a receptor\/PI3K\/Akt signaling pathway","volume":"26","author":"Zhang","year":"2015","journal-title":"Neuroreport"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.neuro.2014.09.007","article-title":"Caffeic acid phenethyl ester (CAPE) protects PC12 cells from MPP+ toxicity by inducing the expression of neuron-typical proteins","volume":"45","author":"Martins","year":"2014","journal-title":"Neurotoxicology"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Yang, S.-H., Liao, C.-C., Chen, Y., Syu, J.-P., Jeng, C.-J., and Wang, S.-M. (2012). Daidzein induces neuritogenesis in DRG neuronal cultures. J. Biomed. Sci., 19.","DOI":"10.1186\/1423-0127-19-80"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"849","DOI":"10.3233\/JAD-2009-1188","article-title":"A diet enriched in polyphenols and polyunsaturated fatty acids, LMN diet, induces neurogenesis in the subventricular zone and hippocampus of adult mouse brain","volume":"18","author":"Valente","year":"2009","journal-title":"J. Alzheimers Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1164","DOI":"10.5114\/aoms.2015.56342","article-title":"Brain-derived neurotrophic factor and its clinical implications","volume":"11","author":"Bathina","year":"2015","journal-title":"Arch. Med. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Martinelli, F., Perrone, A., Yousefi, S., Papini, A., Castiglione, S., Guarino, F., Cicatelli, A., Aelaei, M., Arad, N., and Gholami, M. (2021). Botanical, phytochemical, anti-microbial and pharmaceutical characteristics of hawthorn (Crataegusmonogyna Jacq.), Rosaceae. Molecules, 26.","DOI":"10.3390\/molecules26237266"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Guo, W., Shao, T., Peng, Y., Wang, H., Chen, Z.-S., and Su, H. (2023). Chemical composition, biological activities, and quality standards of hawthorn leaves used in traditional Chinese medicine: A comprehensive review. Front. Pharmacol., 14.","DOI":"10.3389\/fphar.2023.1275244"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1346","DOI":"10.1002\/ptr.7690","article-title":"Neuroprotective effects of hawthorn leaf flavonoids in Abeta(25-35) -induced Alzheimer\u2019s disease model","volume":"37","author":"Xu","year":"2023","journal-title":"Phytother. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"35","DOI":"10.2478\/aucft-2023-0004","article-title":"Content of polyphenolic compounds and biological activity of berries, leaves and flowers of Crataegus L.","volume":"27","author":"Kapsuta","year":"2023","journal-title":"Acta Univ. Cibiniensis. Ser. E Food Technol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Ez-Zahra Amrati, F., Mssillou, I., Boukhira, S., Djiddi Bichara, M., El Abdali, Y., Galvao de Azevedo, R., Mohamed, C., Slighoua, M., Conte, R., and Kiokias, S. (2024). Phenolic composition of Crataegus monogyna Jacq. extract and its anti-inflammatory, hepatoprotective, and antileukemia effects. Pharmaceuticals, 17.","DOI":"10.3390\/ph17060786"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Zhang, L.L., Zhang, L.F., and Xu, J.G. (2020). Chemical composition, antibacterial activity and action mechanism of different extracts from hawthorn (Crataegus pinnatifida Bge.). Sci. Rep., 10.","DOI":"10.1038\/s41598-020-65802-7"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1186\/1742-2094-7-97","article-title":"Immunomodulatory effect of hawthorn extract in an experimental stroke model","volume":"7","author":"Elango","year":"2010","journal-title":"J. Neuroinflammation"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1002\/pca.1081","article-title":"Influence of the extraction mode on the yield of hyperoside, vitexin and vitexin-2\u2033-O-rhamnoside from Crataegus monogyna Jacq. (hawthorn)","volume":"19","author":"Martino","year":"2008","journal-title":"Phytochem. Anal."},{"key":"ref_21","first-page":"49","article-title":"Heat, ultrasound, and microwave assisted extraction methods for recovering bioactive components from hawthorn fruit (Crataegus monogyna Jacq.)","volume":"20","author":"Alsobh","year":"2024","journal-title":"Prog. Agric. Eng. Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.supflu.2013.05.007","article-title":"Optimisation of process variables for antioxidant components from Crataegus. monogyna by supercritical fluid extraction (CO2) using Box-Behnken experimental design","volume":"81","author":"Shortle","year":"2013","journal-title":"J. Supercrit. Fluids"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Sixt, M., and Strube, J. (2018). Systematic design and evaluation of an extraction process for traditionally used herbal medicine on the example of hawthorn (Crataegus monogyna Jacq.). Processes, 6.","DOI":"10.3390\/pr6070073"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"125456","DOI":"10.1016\/j.molliq.2024.125456","article-title":"Use of bulk liquid membranes for the removal of aspartame from aqueous media","volume":"409","author":"Diaconu","year":"2024","journal-title":"J. Mol. Liq."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1002\/pca.2849","article-title":"Ecofriendly microwave-assisted reaction and extraction of bioactive compounds from hawthorn leaf","volume":"30","author":"Hu","year":"2019","journal-title":"Phytochem. Anal."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Belwal, T., Pandey, A., Bhatt, I.D., and Rawal, R.S. (2020). Optimized microwave assisted extraction (MAE) of alkaloids and polyphenols from Berberis roots using multiple-component analysis. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-57585-8"},{"key":"ref_27","first-page":"6614","article-title":"Microwave-assisted extraction of functional compounds from plants: A review","volume":"18","year":"2023","journal-title":"BioResources"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"101655","DOI":"10.1016\/j.scp.2024.101655","article-title":"Sustainable analytical method for determination of bioactive compounds in solid oral formulations (capsules and tablets) containing green tea (Camellia sinensis) marketed in Brazil","volume":"40","author":"Matos","year":"2024","journal-title":"Sustain. Chem. Pharm."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"129995","DOI":"10.1016\/j.foodchem.2021.129995","article-title":"Evaluation of multielement\/proximate composition and bioactive phenolics contents of unconventional edible plants from Brazil using multivariate analysis techniques","volume":"363","author":"Magalhaes","year":"2021","journal-title":"Food Chem."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Ngoc, P.C., Leclercq, L., Rossi, J.C., Desvignes, I., Hertzog, J., Fabiano-Tixier, A.S., Chemat, F., Schmitt-Kopplin, P., and Cottet, H. (2019). Optimizing water-based extraction of bioactive principles of hawthorn: From experimental laboratory research to homemade preparations. Molecules, 24.","DOI":"10.3390\/molecules24234420"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Calcan, S.I., P\u00e2rvulescu, O.C., Ion, V.A., R\u0103ducanu, C.E., B\u0103dulescu, L., Dobre, T., Egri, D., Mo\u021b, A., Popa, V., and Cr\u0103ciun, M.E. (2021). Valorization of vine prunings by slow pyrolysis in a fixed-bed reactor. Processes, 10.","DOI":"10.3390\/pr10010037"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2400","DOI":"10.1111\/j.1365-2621.2010.02416.x","article-title":"Microwave-assisted extraction optimised with response surface methodology and antioxidant activity of polyphenols from hawthorn (Crataegus pinnatifida Bge.) fruit","volume":"45","author":"Liu","year":"2010","journal-title":"Int. J. Food Sci. Technol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Gavrila, A.I., Zalaru, C.M., Tatia, R., Seciu-Grama, A.M., Negrea, C.L., Calinescu, I., Chipurici, P., Trifan, A., and Popa, I. (2023). Green extraction techniques of phytochemicals from Hedera helix L. and in vitro characterization of the extracts. Plants, 12.","DOI":"10.20944\/preprints202311.0492.v1"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.1080\/00986445.2015.1134518","article-title":"Microwave-assisted batch extraction of polyphenols from sea buckthorn leaves","volume":"203","author":"Asofiei","year":"2016","journal-title":"Chem. Eng. Commun."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1007\/s12263-009-0135-4","article-title":"Flavonoids and cognitive function: A review of human randomized controlled trial studies and recommendations for future studies","volume":"4","author":"Macready","year":"2009","journal-title":"Genes Nutr."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1016\/j.foodchem.2009.01.004","article-title":"Phenolic profiles and antioxidative effects of hawthorn cell suspensions, fresh fruits, and medicinal dried parts","volume":"115","author":"Froehlicher","year":"2009","journal-title":"Food Chem."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Lima, L.K.F., Pereira, S.K.S., Junior, R., Santos, F., Nascimento, A.S., Feitosa, C.M., Figueredo, J.S., Cavalcante, A.D.N., Araujo, E., and Rai, M. (2018). A Brief review on the neuroprotective mechanisms of vitexin. BioMed Res. Int., 2018.","DOI":"10.1155\/2018\/4785089"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"4503","DOI":"10.2147\/JIR.S418222","article-title":"Potential implications of hyperoside on oxidative stress-induced human diseases: A comprehensive review","volume":"16","author":"Wang","year":"2023","journal-title":"J. Inflamm. Res."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Fideles, S.O.M., de Cassia Ortiz, A., Buchaim, D.V., de Souza Bastos Mazuqueli Pereira, E., Parreira, M., de Oliveira Rossi, J., da Cunha, M.R., de Souza, A.T., Soares, W.C., and Buchaim, R.L. (2023). Influence of the neuroprotective properties of quercetin on regeneration and functional recovery of the nervous system. Antioxidants, 12.","DOI":"10.3390\/antiox12010149"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"100147","DOI":"10.1016\/j.crgsc.2021.100147","article-title":"Microwave-assisted extraction as an advanced technique for optimisation of limonoid yields and antioxidant potential from Trichilia roka (Meliaceae)","volume":"4","author":"Nana","year":"2021","journal-title":"Curr. Res. Green Sustain. Chem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"603","DOI":"10.2298\/JSC231130006Z","article-title":"Comparative study between homemade and commercial hawthorn (Crataegus spp.) extracts regarding their phenolic profile and antioxidant activity","volume":"89","author":"Zivanovic","year":"2024","journal-title":"J. Serbian Chem. Soc."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.trac.2017.09.002","article-title":"Ultrasonically assisted extraction (UAE) and microwave assisted extraction (MAE) of functional compounds from plant materials","volume":"97","author":"Vinatoru","year":"2017","journal-title":"TrAC Trends Anal. Chem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"108772","DOI":"10.1016\/j.cep.2021.108772","article-title":"Microwave-assisted polyethylene glycol-based aqueous two-phase extraction of gallic acid and ellagic acid from Euonymus alatus: Process optimization, quantification analysis and antioxidant activity","volume":"172","author":"Pi","year":"2022","journal-title":"Chem. Eng. Process."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1016\/S0963-9969(02)00198-9","article-title":"Influence of solvent, matrix dielectric properties, and applied power on the liquid-phase microwave-assisted processes (MAP\u2122) extraction of ginger (Zingiber officinale)","volume":"36","author":"Alfaro","year":"2003","journal-title":"Food Res. Int."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"6213","DOI":"10.1016\/j.chroma.2011.07.040","article-title":"Microwave-assisted extractions of active ingredients from plants","volume":"1218","author":"Chan","year":"2011","journal-title":"J. Chromatogr. A"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"3159","DOI":"10.1080\/10408398.2017.1353480","article-title":"Flavonoids in fruits and vegetables after thermal and nonthermal processing: A review","volume":"58","author":"Ahmed","year":"2018","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/j.trac.2019.05.037","article-title":"Green extraction of natural products. Origins, current status, and future challenges","volume":"118","author":"Chemat","year":"2019","journal-title":"TrAC Trends Anal. Chem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.bej.2010.03.005","article-title":"Design and performance evaluation of a microwave based low carbon yielding extraction technique for naturally occurring bioactive triterpenoid: Oleanolic acid","volume":"50","author":"Mandal","year":"2010","journal-title":"Biochem. Eng. J."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.jfoodeng.2016.05.017","article-title":"A first-principles model for plant cell rupture in microwave-assisted extraction of bioactive compounds","volume":"188","author":"Chan","year":"2016","journal-title":"J. Food Eng."}],"container-title":["Antioxidants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3921\/14\/3\/357\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:55:58Z","timestamp":1760028958000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3921\/14\/3\/357"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,18]]},"references-count":49,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2025,3]]}},"alternative-id":["antiox14030357"],"URL":"https:\/\/doi.org\/10.3390\/antiox14030357","relation":{},"ISSN":["2076-3921"],"issn-type":[{"value":"2076-3921","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,18]]}}}