{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:22:52Z","timestamp":1785410572246,"version":"3.56.0"},"reference-count":49,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T00:00:00Z","timestamp":1776729600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Funds by FCT\u2014Portuguese Foundation for Science and Technology","award":["UID\/04033\/2025"],"award-info":[{"award-number":["UID\/04033\/2025"]}]},{"name":"National Funds by FCT\u2014Portuguese Foundation for Science and Technology","award":["LA\/P\/0126\/2020"],"award-info":[{"award-number":["LA\/P\/0126\/2020"]}]},{"award":["UID\/04033\/2025"],"award-info":[{"award-number":["UID\/04033\/2025"]}],"id":[{"id":"https:\/\/ror.org\/00snfqn58","id-type":"ROR","asserted-by":"publisher"}]},{"award":["LA\/P\/0126\/2020"],"award-info":[{"award-number":["LA\/P\/0126\/2020"]}],"id":[{"id":"https:\/\/ror.org\/00snfqn58","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>Given the established interplay between oxidative stress, cholinergic dysfunction, and metabolic imbalance in cognitive decline, this study investigated the multifunctional potential of three red macroalgae from the Madeira Archipelago (Asparagopsis taxiformis, Grateloupia lanceola, and Nemalion elminthoides) using a sequential biorefinery approach. Marine algae represent a sustainable source of functional food ingredients due to their rich content in bioactive compounds and their compatibility with low-impact production systems. Protein, ethanolic (phenolic-rich), and polysaccharide fractions were obtained through direct extraction and scalable biorefinery processing. Antioxidant activity was evaluated using ORAC, DPPH, FRAP, and FIC assays, while functionality relevant to human health was assessed through acetylcholinesterase, butyrylcholinesterase, and \u03b1-glucosidase inhibition. Protein extracts, particularly from N. elminthoides, exhibited strong hydrogen atom transfer-based antioxidant capacity, whereas ethanolic extracts demonstrated multifunctional activity, combining radical scavenging, metal chelation, and enzyme inhibition associated with neuroprotective and glycemic-regulation potential. Polysaccharide fractions contributed mainly to iron chelation and reducing capacity. Correlation analyses highlighted the complementary nature of antioxidant and bioactivity assays. Overall, these findings support the potential of Madeira red macroalgae as functional food ingredients and emphasize the importance of optimized biorefinery strategies to maximize nutritional and health-related benefits.<\/jats:p>","DOI":"10.3390\/md24040145","type":"journal-article","created":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T07:57:21Z","timestamp":1776758241000},"page":"145","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Red Macroalgae as Sources of Antioxidant and Multifunctional Ingredients for Functional Foods: A Biorefinery Approach"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6166-8045","authenticated-orcid":false,"given":"Nuno","family":"Nunes","sequence":"first","affiliation":[{"name":"ISOPlexis Centre for Sustainable Agriculture and Food Technology, Campus da Penteada, University of Madeira, 9020-105 Funchal, Portugal"},{"name":"Centre for the Research and Technology of Agroenvironmental and Biological Sciences, CITAB, Inov4Agro, Universidade de Tr\u00e1s-os-Montes e Alto Douro, UTAD, Quinta de Prados, 5000-801 Vila Real, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuel","family":"Nunes","sequence":"additional","affiliation":[{"name":"ISOPlexis Centre for Sustainable Agriculture and Food Technology, Campus da Penteada, University of Madeira, 9020-105 Funchal, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kilian","family":"Odenthal","sequence":"additional","affiliation":[{"name":"ISOPlexis Centre for Sustainable Agriculture and Food Technology, Campus da Penteada, University of Madeira, 9020-105 Funchal, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5084-870X","authenticated-orcid":false,"given":"Miguel \u00c2. A. Pinheiro de","family":"Carvalho","sequence":"additional","affiliation":[{"name":"ISOPlexis Centre for Sustainable Agriculture and Food Technology, Campus da Penteada, University of Madeira, 9020-105 Funchal, Portugal"},{"name":"Centre for the Research and Technology of Agroenvironmental and Biological Sciences, CITAB, Inov4Agro, Universidade de Tr\u00e1s-os-Montes e Alto Douro, UTAD, Quinta de Prados, 5000-801 Vila Real, Portugal"},{"name":"Faculty of Life Sciences, Campus da Penteada, University of Madeira, 9020-105 Funchal, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"El-Beltagi, H.S., Mohamed, A.A., Mohamed, H.I., Ramadan, K.M.A., Barqawi, A.A., and Mansour, A.T. (2022). Phytochemical and potential properties of seaweeds and their recent applications: A review. Mar. Drugs, 20.","DOI":"10.3390\/md20060342"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"128479","DOI":"10.1016\/j.ijbiomac.2023.128479","article-title":"Red seaweed biorefinery: The influence of sequential extractions on the functional properties of extracted agars and porphyrans","volume":"257","author":"Teixeira","year":"2024","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e00957","DOI":"10.1016\/j.heliyon.2018.e00957","article-title":"Nutraceutical potential of Asparagopsis taxiformis extracts and assessment of a downstream purification strategy","volume":"4","author":"Nunes","year":"2018","journal-title":"Heliyon"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1515\/bot-2019-0022","article-title":"Biochemical study of attached macroalgae from the Madeira Archipelago and beach-cast macroalgae from the Canary Islands: Multivariate analysis to determine bioresource potential","volume":"63","author":"Nunes","year":"2020","journal-title":"Bot. Mar."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"103243","DOI":"10.1016\/j.algal.2023.103243","article-title":"Novel biorefinery process for extraction of laminarin, alginate and protein from brown seaweed using hydrodynamic cavitation","volume":"74","author":"Zhu","year":"2023","journal-title":"Algal Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"142166","DOI":"10.1016\/j.jclepro.2024.142166","article-title":"Red seaweed as an abundant, natural methanogenesis inhibitor for industrial biorefinery","volume":"454","author":"Tenci","year":"2024","journal-title":"J. Clean. Prod."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"102798","DOI":"10.1016\/j.algal.2022.102798","article-title":"Changes in antioxidant activity of fresh marine macroalgae from the Canary Islands during the air-drying process","volume":"66","year":"2022","journal-title":"Algal Res."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Castej\u00f3n, N., Parailloux, M., Izdebska, A., Lobinski, R., and Fernandes, S.C.M. (2021). Valorization of the red algae Gelidium sesquipedale by extracting a broad spectrum of minor compounds using green approaches. Mar. Drugs, 19.","DOI":"10.3390\/md19100574"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1404","DOI":"10.1016\/j.toxrep.2021.07.006","article-title":"In vitro antioxidant study of polyphenol from red seaweeds dichotomously branched Gracilaria edulis and robust sea moss Hypnea valentiae","volume":"8","author":"Mahendran","year":"2021","journal-title":"Toxicol. Rep."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Freitas, M.V., In\u00e1cio, L.G., Ruas, A., Silva, I.A., Mouga, T., Pereira, L., and Afonso, C. (2023). Antioxidant and antimicrobial properties of selected red seaweeds from central Portugal. Appl. Sci., 13.","DOI":"10.3390\/app13010157"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"103609","DOI":"10.1016\/j.algal.2024.103609","article-title":"LC\u2013ESI\u2013QTOF\u2013MS\/MS characterization of phenolic compounds from Victorian shorebound red seaweeds and their antioxidant capacity","volume":"82","author":"Ebrahimi","year":"2024","journal-title":"Algal Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.jff.2019.03.004","article-title":"Design of low glycemic response foods using polyphenols from seaweed","volume":"56","author":"Parada","year":"2019","journal-title":"J. Funct. Foods"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1111\/jpy.12640","article-title":"The influence of environmental features in the content of mycosporine-like amino acids in red marine algae along the Brazilian coast","volume":"54","author":"Briani","year":"2018","journal-title":"J. Phycol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1007\/s10811-008-9345-1","article-title":"Antioxidant activity of mycosporine-like amino acids isolated from three red macroalgae and one marine lichen","volume":"21","author":"Aguilera","year":"2009","journal-title":"J. Appl. Phycol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"120965","DOI":"10.1016\/j.carbpol.2023.120965","article-title":"The antioxidant activity of polysaccharides: A structure\u2013function relationship overview","volume":"314","author":"Fernandes","year":"2023","journal-title":"Carbohydr. Polym."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1016\/j.neuron.2025.02.014","article-title":"Multi-cohort cerebrospinal fluid proteomics identifies robust molecular signatures across the Alzheimer disease continuum","volume":"113","author":"Ali","year":"2025","journal-title":"Neuron"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1007\/s10811-019-01884-9","article-title":"Fatty acid composition, TLC screening, ATR-FTIR analysis, anti-cholinesterase activity, and in vitro cytotoxicity to the A549 tumor cell line of extracts from three macroalgae collected in Madeira","volume":"32","author":"Nunes","year":"2020","journal-title":"J. Appl. Phycol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Martens, N., Zhan, N., Yam, S.C., Leijten, F.P.J., Palumbo, M., Caspers, M., Tiane, A., Friedrichs, S., Li, Y., and van Vark\u2013van der Zee, L. (2024). Supplementation of seaweed extracts to the diet reduces symptoms of Alzheimer\u2019s disease in the APPswePS1\u0394E9 mouse model. Nutrients, 16.","DOI":"10.3390\/nu16111614"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/S0166-2236(03)00067-5","article-title":"The metallobiology of Alzheimer\u2019s disease","volume":"26","author":"Bush","year":"2003","journal-title":"Trends Neurosci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1038\/nrd1330","article-title":"Neurodegenerative diseases and oxidative stress","volume":"3","author":"Barnham","year":"2004","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.2147\/VHRM.S3119","article-title":"Alpha-glucosidase inhibitors in the early treatment of type 2 diabetes","volume":"4","year":"2008","journal-title":"Vasc. Health Risk Manag."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"35","DOI":"10.2174\/156720512799015037","article-title":"Brain insulin resistance and deficiency as therapeutic targets in Alzheimer\u2019s disease","volume":"9","year":"2012","journal-title":"Curr. Alzheimer Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1038\/nrneurol.2017.185","article-title":"Brain insulin resistance in type 2 diabetes and Alzheimer disease: Concepts and conundrums","volume":"14","author":"Arnold","year":"2018","journal-title":"Nat. Rev. Neurol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1038\/s41583-019-0132-6","article-title":"Oxidative stress, dysfunctional glucose metabolism and Alzheimer disease","volume":"20","author":"Butterfield","year":"2019","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1016\/j.foodhyd.2018.07.047","article-title":"Extraction of proteins from two marine macroalgae, Ulva sp. and Gracilaria sp., for food application, and evaluating digestibility, amino acid composition and antioxidant properties of the protein concentrates","volume":"87","author":"Kazir","year":"2019","journal-title":"Food Hydrocoll."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1509","DOI":"10.1007\/s11101-022-09826-z","article-title":"Biological properties and potential of compounds extracted from red seaweeds","volume":"22","author":"Carpena","year":"2022","journal-title":"Phytochem. Rev."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1515\/BOT.2009.037","article-title":"Antioxidant and cytotoxic activities of some red algae (Rhodophyta) from Brittany coasts (France)","volume":"52","author":"Zubia","year":"2009","journal-title":"Bot. Mar."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1841","DOI":"10.1021\/jf030723c","article-title":"The chemistry behind antioxidant capacity assays","volume":"53","author":"Huang","year":"2005","journal-title":"J. Agric. Food Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1016\/0891-5849(95)02227-9","article-title":"Structure\u2013antioxidant activity relationships of flavonoids and phenolic acids","volume":"20","author":"Miller","year":"1996","journal-title":"Free Radic. Biol. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"735088","DOI":"10.1016\/j.aquaculture.2020.735088","article-title":"Antioxidant activity of extracts from marine macroalgae, wild-collected and cultivated, in an integrated multitrophic aquaculture system","volume":"522","author":"Vega","year":"2020","journal-title":"Aquaculture"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2427","DOI":"10.1007\/s10811-017-1074-x","article-title":"Biochemical composition, nutritional value, and antioxidant properties of seven seaweed species from the Madeira Archipelago","volume":"29","author":"Nunes","year":"2017","journal-title":"J. Appl. Phycol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.ijbiomac.2007.10.003","article-title":"Antioxidant activity of sulfated polysaccharide fractions extracted from Laminaria japonica","volume":"42","author":"Wang","year":"2008","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1016\/j.jfoodeng.2013.01.014","article-title":"Techniques for extraction of bioactive compounds from plant materials: A review","volume":"117","author":"Azmir","year":"2013","journal-title":"J. Food Eng."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1016\/j.jff.2015.06.018","article-title":"Phenolics and polyphenolics in foods, beverages and spices: Antioxidant activity and health effects\u2014A review","volume":"18","author":"Shahidi","year":"2015","journal-title":"J. Funct. Foods"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.3233\/JAD-161088","article-title":"Oxidative stress, synaptic dysfunction, and Alzheimer\u2019s disease","volume":"57","author":"Trushina","year":"2017","journal-title":"J. Alzheimers Dis."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"315","DOI":"10.2174\/1570159X11311030006","article-title":"Acetylcholinesterase inhibitors: Pharmacology and toxicology","volume":"11","year":"2013","journal-title":"Curr. Neuropharmacol."},{"key":"ref_37","first-page":"1","article-title":"Biorefinery of red macroalgae from the Madeira Archipelago for value-added products","volume":"38","author":"Nunes","year":"2026","journal-title":"J. Appl. Phycol."},{"key":"ref_38","unstructured":"Thermo Fisher Scientific (2016). Antioxidant Capacity ORAC Protocol, Thermo Fisher Scientific. Available online: https:\/\/assets.thermofisher.com\/TFS-Assets\/LED\/Application-Notes\/Antioxidant-Capacity-AN-VarioskanLUX-ORAC-EN.pdf."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.foodchem.2004.12.015","article-title":"Evaluation of antioxidant property of extract and fractions obtained from a red alga, Polysiphonia urceolata","volume":"95","author":"Duan","year":"2006","journal-title":"Food Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1021\/jf00049a007","article-title":"Antioxidant activity of various tea extracts in relation to their antimutagenicity","volume":"43","author":"Yen","year":"1995","journal-title":"J. Agric. Food Chem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"307","DOI":"10.5264\/eiyogakuzashi.44.307","article-title":"Studies on products of browning reaction: Antioxidative activities of products of browning reaction prepared from glucosamine","volume":"44","author":"Oyaizu","year":"1986","journal-title":"Jpn. J. Nutr. Diet."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1016\/j.fct.2005.02.012","article-title":"Extracts from dulse (Palmaria palmata) are effective antioxidants and inhibitors of cell proliferation in vitro","volume":"43","author":"Yuan","year":"2005","journal-title":"Food Chem. Toxicol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1016\/j.lwt.2007.06.013","article-title":"Antioxidant activity of three edible seaweeds from two areas in South East Asia","volume":"41","author":"Chew","year":"2008","journal-title":"LWT\u2014Food Sci. Technol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1021\/jf00093a019","article-title":"Role of ferritin as a lipid oxidation catalyst in muscle food","volume":"38","author":"Decker","year":"1990","journal-title":"J. Agric. Food Chem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"3082","DOI":"10.3390\/molecules17033082","article-title":"Anti-acetylcholinesterase and antioxidant activity of essential oils from Hedychium gardnerianum Sheppard ex Ker-Gawl","volume":"17","author":"Arruda","year":"2012","journal-title":"Molecules"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/0006-2952(61)90145-9","article-title":"A new and rapid colorimetric determination of acetylcholinesterase activity","volume":"7","author":"Ellman","year":"1961","journal-title":"Biochem. Pharmacol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1186\/s13065-018-0445-y","article-title":"Inhibitory effects against \u03b1-glucosidase and \u03b1-amylase of the flavonoid-rich extract from Scutellaria baicalensis shoots and interpretation of structure\u2013activity relationship of its eight flavonoids by a refined assign-score method","volume":"12","author":"Li","year":"2018","journal-title":"Chem. Cent. J."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"13014","DOI":"10.1021\/acsomega.0c00929","article-title":"In vitro evaluation of antidiabetic and anti-inflammatory activities of polyphenolic-rich extracts from Anchusa officinalis and Melilotus officinalis","volume":"5","author":"Paun","year":"2020","journal-title":"ACS Omega"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"4676","DOI":"10.1016\/j.biortech.2010.01.093","article-title":"Phenolic compounds, antioxidant activity and in vitro inhibitory potential against key enzymes relevant for hyperglycemia and hypertension of commonly used medicinal plants, herbs and spices in Latin America","volume":"101","author":"Ranilla","year":"2010","journal-title":"Bioresour. Technol."}],"container-title":["Marine Drugs"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-3397\/24\/4\/145\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T08:02:26Z","timestamp":1776758546000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-3397\/24\/4\/145"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,21]]},"references-count":49,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["md24040145"],"URL":"https:\/\/doi.org\/10.3390\/md24040145","relation":{},"ISSN":["1660-3397"],"issn-type":[{"value":"1660-3397","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,21]]}}}