{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T18:50:02Z","timestamp":1789671002127,"version":"4.0.1"},"reference-count":47,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,2,16]],"date-time":"2023-02-16T00:00:00Z","timestamp":1676505600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"EU program","award":["PRIMA-S2-2018-PCI2019-103453"],"award-info":[{"award-number":["PRIMA-S2-2018-PCI2019-103453"]}]},{"name":"Research and Innovation in the Mediterranean Area, PRIMA","award":["PRIMA-S2-2018-PCI2019-103453"],"award-info":[{"award-number":["PRIMA-S2-2018-PCI2019-103453"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The orange byproduct is a widely accessible and valuable source of functional phenolic compounds, particularly hesperidin. Hesperidin extraction remains a challenging phase in its valorization chain due to its low solubility and limited extractability in solvents. This work aims to examine the effect of conventional solvent extraction (CSE) compared to emerging and innovative extraction methods: accelerated solvent extraction (ASE) and ultrasound-assisted extraction (UAE) when applied with or without a pretreatment process of instant controlled pressure drop (DIC) to intensify extraction, antioxidant, and antidiabetic activities. The total phenols, flavonoids, hesperidin contents, radical scavenging activities, iron chelating activity, and in vitro \u03b1-amylase inhibition of the extracts were determined for CSE (80%, 70 \u00b0C), UAE (ethanol 80%, 70 \u00b0C, 200 W), and ASE (ethanol 60%, 100 \u00b0C, 100 bars) with or without DIC pretreatment (pressure = 0.4 MPa, total thermal time = 30 s). The hesperidin amounts obtained were 0.771 \u00b1 0.008 g\/100 g DM, 0.823 \u00b1 0.054 g\/100 g DM, and 1.368 \u00b1 0.058 g\/100 g DM, for CSE, UAE, and ASE, respectively. DIC pretreatment of orange byproducts increased hesperidin recovery by 67%, 25.6%, and 141% for DIC-CSE, DIC-UAE, and DIC-ASE, respectively. The DPPH and ABTS radical scavenging and iron chelating activities of extracts were also significantly enhanced, and the in vitro antidiabetic activity of extracts was preserved.<\/jats:p>","DOI":"10.3390\/molecules28041858","type":"journal-article","created":{"date-parts":[[2023,2,16]],"date-time":"2023-02-16T01:36:52Z","timestamp":1676511412000},"page":"1858","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Intensifying Effect of Instant Controlled Pressure Drop (DIC) Pre-Treatment on Hesperidin Recovery from Orange Byproducts: In Vitro Antioxidant and Antidiabetic Activities of the Extracts"],"prefix":"10.3390","volume":"28","author":[{"given":"Mariem","family":"Ben Abdallah","sequence":"first","affiliation":[{"name":"Laboratoire de Physiopathologie, Alimentation et Biomol\u00e9cules, LR17ES03, Institut Sup\u00e9rieur de Biotechnologie de Sidi Thabet, Universit\u00e9 de la Manouba, Ariana 2020, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3758-1967","authenticated-orcid":false,"given":"Morad","family":"Chadni","sequence":"additional","affiliation":[{"name":"URD Agro-Biotechnologies Industrielles (ABI), CEBB, AgroParisTech, 51110 Pomacle, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nouha","family":"M\u2019hiri","sequence":"additional","affiliation":[{"name":"Laboratoire de Physiopathologie, Alimentation et Biomol\u00e9cules, LR17ES03, Institut Sup\u00e9rieur de Biotechnologie de Sidi Thabet, Universit\u00e9 de la Manouba, Ariana 2020, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0357-4670","authenticated-orcid":false,"given":"Fanny","family":"Brunissen","sequence":"additional","affiliation":[{"name":"URD Agro-Biotechnologies Industrielles (ABI), CEBB, AgroParisTech, 51110 Pomacle, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nesrine","family":"Rokbeni","sequence":"additional","affiliation":[{"name":"Laboratoire de Physiopathologie, Alimentation et Biomol\u00e9cules, LR17ES03, Institut Sup\u00e9rieur de Biotechnologie de Sidi Thabet, Universit\u00e9 de la Manouba, Ariana 2020, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karim","family":"Allaf","sequence":"additional","affiliation":[{"name":"Laboratoire des Sciences de l\u2019Ing\u00e9nieur pour l\u2019Environnement (LaSIE), UMR-CNRS-7356, Facult\u00e9 des Sciences et Technologies, La Rochelle Universit\u00e9, CEDEX 1, 17042 La Rochelle, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8961-1542","authenticated-orcid":false,"given":"Colette","family":"Besombes","sequence":"additional","affiliation":[{"name":"Laboratoire des Sciences de l\u2019Ing\u00e9nieur pour l\u2019Environnement (LaSIE), UMR-CNRS-7356, Facult\u00e9 des Sciences et Technologies, La Rochelle Universit\u00e9, CEDEX 1, 17042 La Rochelle, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1914-2717","authenticated-orcid":false,"given":"Irina","family":"Ioannou","sequence":"additional","affiliation":[{"name":"URD Agro-Biotechnologies Industrielles (ABI), CEBB, AgroParisTech, 51110 Pomacle, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nourhene","family":"Boudhrioua","sequence":"additional","affiliation":[{"name":"Laboratoire de Physiopathologie, Alimentation et Biomol\u00e9cules, LR17ES03, Institut Sup\u00e9rieur de Biotechnologie de Sidi Thabet, Universit\u00e9 de la Manouba, Ariana 2020, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,16]]},"reference":[{"key":"ref_1","unstructured":"Citrus World Statistics (2022, November 21). Edition 2022. New Citrus World Statistics Publication. Available online: https:\/\/fruittoday.com\/en\/new-citrus-world-statistics-publication\/."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1080\/87559129.2014.924139","article-title":"Extraction methods of citrus peel phenolic compounds: A review","volume":"30","author":"Ioannou","year":"2014","journal-title":"Food Rev. Int."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1080\/87559129.2016.1196489","article-title":"Phytochemical characteristics of Citrus peel and effect of conventional and nonconventional processing on phenolic compounds: A review","volume":"33","author":"Ioannou","year":"2017","journal-title":"Food Rev. Int."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"560","DOI":"10.4103\/0975-2870.192146","article-title":"Ethno medicinal values of Citrus genus: A review","volume":"9","author":"Chaudhari","year":"2016","journal-title":"Med. J. DY Patil Univ."},{"key":"ref_5","first-page":"224","article-title":"Hypoglycaemic and anti-diabetic activity of selected African medicinal plants","volume":"11","author":"Oguntibeju","year":"2019","journal-title":"Int. J. Physiol. Pathophysiol. Pharmacol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"109114","DOI":"10.1016\/j.foodres.2020.109114","article-title":"Phenolic composition, antioxidant potential and health benefits of citrus peel","volume":"132","author":"Singh","year":"2020","journal-title":"Food Res. Int."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"515","DOI":"10.4172\/2157-7439.1000515","article-title":"Anticancer Activities of Hesperidin and Hesperetin In vivo and their Potentiality against Bladder Cancer","volume":"9","author":"Stanisic","year":"2018","journal-title":"J. Nanomed. Nanotechnol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1969","DOI":"10.1111\/1541-4337.12561","article-title":"Valorization of pomelo (Citrus grandis Osbeck) peel: A review of current utilization, phytochemistry, bioactivities, and mechanisms of action","volume":"19","author":"Tocmo","year":"2020","journal-title":"Compr. Rev. Food Sci. Food Saf."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1080\/10408398.2011.653734","article-title":"Therapeutic and Nutraceutical Potential of Bioactive Compounds Extracted from Fruit Residues","volume":"55","author":"Babbar","year":"2014","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Pyrzynska, K. (2022). Hesperidin: A Review on Extraction Methods, Stability and Biological Activities. Nutrients, 14.","DOI":"10.3390\/nu14122387"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Benayad, O., Bouhrim, M., Tiji, S., Kharchoufa, L., Addi, M., Drouet, S., Hano, C., Lorenzo, J.M., Bendaha, H., and Bnouham, M. (2021). Phytochemical Profile, \u03b1-Glucosidase, and \u03b1-Amylase Inhibition Potential and Toxicity Evaluation of Extracts from Citrus aurantium (L.) Peel, a Valuable By-Product from Northeastern Morocco. Biomolecules., 11.","DOI":"10.3390\/biom11111555"},{"key":"ref_12","first-page":"414","article-title":"Antioxidant and In-vitro Antidiabetic Activities of Fermented Peels of Citrus x Sinensis (L.) Osbeck (Rutaceae)","volume":"4","author":"Asabi","year":"2021","journal-title":"Prog. Chem. Biochem. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1080\/10408398.2014.906382","article-title":"Health-promoting effects of the citrus flavonone hesperidin","volume":"57","author":"Li","year":"2017","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1002\/ptr.6046","article-title":"Blood pressure lowering and anti-inflammatory effects of hesperidin in type 2 diabetes; a randomized double-blind controlled clinical trial","volume":"32","author":"Homayouni","year":"2018","journal-title":"Phytother Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1539","DOI":"10.1002\/ptr.5881","article-title":"Hesperidin Supplementation Alleviates Oxidative DNA Damage and Lipid Peroxidation in Type 2 Diabetes: A Randomized Double-Blind Placebo-Controlled Clinical Trial","volume":"31","author":"Homayouni","year":"2017","journal-title":"Phytother Res."},{"key":"ref_16","first-page":"1","article-title":"Pharmacological Significance of Hesperidin and Hesperetin, Two Citrus Flavonoids, as Promising Antiviral Compounds for Prophylaxis Against and Combating COVID-19","volume":"16","author":"Agrawal","year":"2021","journal-title":"Nat. Prod. Commun."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Padilla de la Rosa, D., Ruiz-Palomino, P., Guadalupe, M., Garc\u00eda-Fajardo, J., Sandoval-Fabi\u00e1n, G., and Arriola-Guevara, E. (2018). A Green Process for the Extraction and Purification of Hesperidin from Mexican Lime Peel (Citrus aurantifolia Swingle) that is Extendible to the Citrus Genus. Processes, 6.","DOI":"10.20944\/preprints201811.0413.v1"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1016\/j.jfoodeng.2011.12.019","article-title":"Enhanced extraction of flavanones hesperidin and narirutin from Citrus unshiu peel using subcritical water","volume":"110","author":"Cheigh","year":"2012","journal-title":"J. Food Eng."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"105625","DOI":"10.1016\/j.ultsonch.2021.105625","article-title":"Review of ultrasound combinations with hybrid and innovative techniques for extraction and processing of food and natural products","volume":"76","author":"Khadhraoui","year":"2021","journal-title":"Ultrason Sonochem."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Mahato, N., Sinha, M., Sharma, K., Koteswararao, R., and Cho, H.M. (2019). Modern Extraction and Purification Techniques for Obtaining High Purity Food-Grade Bioactive Compounds and Value-Added Co-Products from Citrus Wastes. Foods, 8.","DOI":"10.3390\/foods8110523"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Anticona, M., Blesa, J., Frigola, A., and Esteve, M.J. (2020). High Biological Value Compounds Extraction from Citrus Waste with Non-Conventional Methods. Foods, 9.","DOI":"10.3390\/foods9060811"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1016\/j.foodchem.2010.04.051","article-title":"Isolation of hesperidin from peels of thinned Citrus unshiu fruits by microwave-assisted extraction","volume":"123","author":"Inoue","year":"2010","journal-title":"Food Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1016\/j.foodchem.2015.04.081","article-title":"Comparison of microwave, ultrasound and accelerated-assisted solvent extraction for recovery of polyphenols from Citrus sinensis peels","volume":"187","author":"Nayak","year":"2015","journal-title":"Food Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.fbp.2015.07.010","article-title":"Effect of different operating conditions on the extraction of phenolic compounds in orange peel","volume":"96","author":"Ioannou","year":"2015","journal-title":"Food Bioprod. Process."},{"key":"ref_25","first-page":"161","article-title":"Antioxidants of Maltease orange peel: Comparative investigation of the efficiency of four extraction methods","volume":"96","author":"Ioannou","year":"2017","journal-title":"J. Appl. Pharm. Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"114337","DOI":"10.1016\/j.lwt.2022.114337","article-title":"Extraction and recovery of bioactive soluble phenolic compounds from brocade orange (Citrus sinensis) peels: Effect of different extraction methods thereon","volume":"173","author":"Wang","year":"2023","journal-title":"LWT"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Chadni, M., Isidore, E., Diemer, E., Ouguir, O., Brunois, F., Catteau, R., Cassan, L., and Ioannou, I. (2022). Optimization of Extraction Conditions to Improve Chlorogenic Acid Content and Antioxidant Activity of Extracts from Forced Witloof Chicory Roots. Foods, 11.","DOI":"10.3390\/foods11091217"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1016\/j.jfda.2016.07.010","article-title":"Extraction and quantification of polyphenols from kinnow (Citrus reticulate L.) peel using ultrasound and maceration techniques","volume":"25","author":"Safdar","year":"2017","journal-title":"J Food Drug Anal."},{"key":"ref_29","first-page":"2268","article-title":"Optimization conditions of ultrasound-assisted extraction of phenolic compounds from orange peels using response surface methodology","volume":"27","author":"Shehata","year":"2021","journal-title":"J. Food Process. Preserv."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2","DOI":"10.26577\/ijbch-2019-v2-2","article-title":"Optimization of conditions of ultrasound-assisted extraction of phenolic compounds from orange pomace (Citrus sinensis)","volume":"12","author":"Ghasempour","year":"2019","journal-title":"Int. J. Biol. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1016\/j.foodchem.2009.08.046","article-title":"Ultrasound-assisted extraction of polyphenols (flavanone glycosides) from orange (Citrus sinensis L.) peel","volume":"119","author":"Khan","year":"2010","journal-title":"Food Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.fbp.2018.08.006","article-title":"Recovery of phenolic compounds from citrus by-products using pressurized liquids\u2013an application to orange peel","volume":"112","author":"Barrales","year":"2018","journal-title":"Food Bioprod. Process."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.ifset.2012.10.005","article-title":"Improving the pressing extraction of polyphenols of orange peel by pulsed electric fields","volume":"17","author":"Luengo","year":"2013","journal-title":"Innov. Food Sci. Emerg. Technol."},{"key":"ref_34","first-page":"4917","article-title":"Optimization and comparison of nonconventional extraction techniques for soluble phenolic compounds from brocade orange (Citrus sinensis) peels","volume":"87","author":"Wang","year":"2022","journal-title":"Food Chem."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Repaji, M., Cegledi, E., Kruk, V., Pedisi, S., \u00c7\u0131nar, F., Kovacevi, B.D., \u017duti, I., and Dragovi\u00b4-Uzelac, V. (2020). Accelerated Solvent Extraction as a Green Tool for the Recovery of Polyphenols and Pigments from Wild Nettle Leaves. Processes, 8.","DOI":"10.3390\/pr8070803"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1111\/1750-3841.15016","article-title":"Intensification of polyphenols extraction from orange peels using infrared as a novel and energy saving pretreatment","volume":"85","author":"Rajha","year":"2020","journal-title":"J. Food Sci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1016\/j.proeng.2012.07.498","article-title":"Instant Controlled Pressure Drop Combined to Ultrasounds as Innovative Extraction Process Combination: Fundamental Aspects","volume":"42","author":"Allaf","year":"2012","journal-title":"Procedia Eng."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Allaf, T., Besombes, C., Tomao, V., Chemat, F., and Allaf, K. (2014). Instant Controlled Pressure Drop (D.I.C.), Springer. Chapter Part III.","DOI":"10.1007\/978-1-4614-8669-5"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/j.ultsonch.2012.05.013","article-title":"Instant controlled pressure drop technology and ultrasound assisted extraction for sequential extraction of essential oil and antioxidants","volume":"20","author":"Allaf","year":"2013","journal-title":"Ultrason Sonochem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.fbp.2018.11.012","article-title":"Instant Controlled Pressure-Drop as Texturing Pretreatment for Intensifying both Final Drying Stage and Extraction of Phenolic Compounds to valorize Orange Industry By-products (Citrus Sinensis L.)","volume":"114","author":"Louati","year":"2018","journal-title":"Food Bioprod. Process."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1111\/jtxs.12468","article-title":"Texture and Color Characteristics of Swell Dried Ready-to-Eat Zaghloul Date Snacks: Effect of Operative Parameters of Instant Controlled Pressure Drop Process","volume":"51","author":"Mounir","year":"2019","journal-title":"J. Texture Stud."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1007\/s11694-016-9407-z","article-title":"Cactus pear peel snacks prepared by instant pressure drop texturing: Effect of process variables on bioactive compounds and functional properties","volume":"11","author":"Namir","year":"2016","journal-title":"J. Food Meas. Charact."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1674","DOI":"10.1007\/s11947-018-2133-2","article-title":"Engineering Texture Properties of Instant Controlled Pressure Drop (DIC) Dried Carrot Chips via Modulating Osmotic Conditions","volume":"11","author":"Peng","year":"2018","journal-title":"Food Bioproc. Tech."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Chen, Q., Wang, D., Tan, C., Hu, Y., Sundararajan, B., and Zhou, Z. (2020). Profiling of flavonoid and antioxidant activity of fruit tissues from 27 Chinese local citrus cultivars. Plants, 9.","DOI":"10.3390\/plants9020196"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1016\/S0924-2244(01)00027-9","article-title":"Some methodical problems in the determination of antioxidant activity using chromogen radicals: A practical case","volume":"11","author":"Arnao","year":"2000","journal-title":"Trends Food Sci. Technol."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Diemer, E., Chadni, M., Grimi, N., and Ioannou, I. (2022). Optimization of the Accelerated Solvent Extraction of Caffeoylquinic Acids from Forced Chicory Roots and Antioxidant Activity of the Resulting Extracts. Foods, 11.","DOI":"10.3390\/foods11203214"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1007\/s13197-010-0222-y","article-title":"Characterization of the antioxidant properties of phenolic extracts from some citrus peels","volume":"49","author":"Oboh","year":"2011","journal-title":"J. Food Sci. Technol."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/28\/4\/1858\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:37:15Z","timestamp":1760121435000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/28\/4\/1858"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,16]]},"references-count":47,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["molecules28041858"],"URL":"https:\/\/doi.org\/10.3390\/molecules28041858","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,16]]}}}