{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T15:59:37Z","timestamp":1790006377533,"version":"4.0.1"},"reference-count":46,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T00:00:00Z","timestamp":1784160000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004480","name":"Natural Science Foundation of Shanxi Province","doi-asserted-by":"publisher","award":["202503021211101"],"award-info":[{"award-number":["202503021211101"]}],"id":[{"id":"10.13039\/501100004480","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Foods"],"abstract":"<jats:p>The sustainable isolation of nonamphiphilic phytochemicals remains a formidable challenge in biochemical engineering. In this study, a highly efficient and solvent free foam fractionation process was developed for recovering rosmarinic acid from botanical extracts. By systematically screening diverse biological surfactants, whey soy protein emerged as an exceptionally robust dual functional frother and nanoscale collector. Response surface methodology optimized the operational parameters to 850 mg\/L protein concentration, pH 2.5, and a gas flow rate of 470 mL\/min, yielding an outstanding target recovery of 93.08 percent alongside an enrichment ratio of 1.81. This macroscopic separation superiority was comprehensively elucidated at the molecular level through multiple spectroscopic techniques and computational modeling. Results confirmed a spontaneous static quenching complexation driven by synergistic noncovalent forces, predominantly hydrogen bonding, van der Waals interactions, \u03c0-stacking, and salt bridges. These interactions induced targeted conformational unfolding within the protein backbone, exposing hydrophobic domains that drastically elevated the thermodynamic affinity for the ascending gas\u2013liquid interface. Furthermore, the concentrated product exhibited an antioxidant capacity enhancement exceeding 3.6 times compared to the crude extract, a result attributed to selective enrichment combined with the structural shielding effect provided by the protein macromolecule. Ultimately, this work provides critical mechanistic insights and establishes a scalable technological framework for the green purification of highly valuable botanical compounds.<\/jats:p>","DOI":"10.3390\/foods15142525","type":"journal-article","created":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T00:55:59Z","timestamp":1784249759000},"page":"2525","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Green Recovery of Rosmarinic Acid via Whey Soy Protein-Mediated Foam Fractionation: Molecular Mechanisms and Enhanced Antioxidant Activity"],"prefix":"10.3390","volume":"15","author":[{"given":"Yanfei","family":"Li","sequence":"first","affiliation":[{"name":"School of Chemistry and Chemical Engineering, North University of China, Taiyuan 030051, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Run","family":"Yang","sequence":"additional","affiliation":[{"name":"School of Chemistry and Chemical Engineering, North University of China, Taiyuan 030051, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongjie","family":"Xiang","sequence":"additional","affiliation":[{"name":"School of Chemistry and Chemical Engineering, North University of China, Taiyuan 030051, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhirong","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Chemistry and Chemical Engineering, North University of China, Taiyuan 030051, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhijun","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Chemistry and Chemical Engineering, North University of China, Taiyuan 030051, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nan","family":"Hu","sequence":"additional","affiliation":[{"name":"School of Chemistry and Chemical Engineering, North University of China, Taiyuan 030051, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4172","DOI":"10.1080\/10408398.2024.2384643","article-title":"Macroalgae-derived bioactive compounds for functional food and pharmaceutical applications\u2014A critical review","volume":"65","author":"Kaur","year":"2025","journal-title":"Crit. Rev. Food. Sci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"119943","DOI":"10.1016\/j.carbpol.2022.119943","article-title":"Preparation of chitosan-rosmarinic acid derivatives with enhanced antioxidant and anti-inflammatory activities","volume":"296","author":"Zhang","year":"2022","journal-title":"Carbohyd. Polym."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"118559","DOI":"10.1016\/j.indcrop.2024.118559","article-title":"Natural deep eutectic solvents-mediated extraction of rosmarinic acid from Lamiaceae plants: Enhanced extractability and anti-inflammatory potential","volume":"214","author":"Uka","year":"2024","journal-title":"Ind. Crop. Prod."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"8838","DOI":"10.1021\/acs.jafc.2c03104","article-title":"Quantitative comparison and chemical profile analysis of different medicinal parts of Perilla frutescens (L.) Britt. from different varieties and harvest periods","volume":"70","author":"Fan","year":"2022","journal-title":"J. Agric. Food Chem."},{"key":"ref_5","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_6","doi-asserted-by":"crossref","first-page":"156542","DOI":"10.1016\/j.cej.2024.156542","article-title":"Tungsten-rosmarinic acid nanoenzyme with SOD mimetic activity for the treatment of psoriasis by eliminating ROS and relieving inflammation","volume":"499","author":"Su","year":"2024","journal-title":"Chem. Eng. J."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"137540","DOI":"10.1016\/j.foodchem.2023.137540","article-title":"New selective and sustainable ultrasound-assisted extraction procedure to recover carnosic and rosmarinic acids from Rosmarinus officinalis by sequential use of bio-based solvents","volume":"435","author":"Pizani","year":"2024","journal-title":"Food Chem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"110485","DOI":"10.1016\/j.microc.2024.110485","article-title":"Development and validation of an efficient approach for extracting essential oil, scutellarin, and rosmarinic acid from Perilla frutescens leaves using vacuum microwave-mediated rotary hydrodistillation and extraction in situ and a choline amino acid ionic liquid","volume":"200","author":"Feng","year":"2024","journal-title":"Microchem. J."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"132935","DOI":"10.1016\/j.seppur.2025.132935","article-title":"Recovery of quinoa protein via ultrasound-assisted extraction and nanoparticle-enhanced foam fractionation: Stabilizer preparation, mechanistic insights and process optimization","volume":"367","author":"Hu","year":"2025","journal-title":"Sep. Purif. Technol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"147016","DOI":"10.1016\/j.foodchem.2025.147016","article-title":"Engineering bifunctional amino-cellulose nanofibers for high-efficiency foam fractionation of flavonoids","volume":"497","author":"Hu","year":"2025","journal-title":"Food Chem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"119532","DOI":"10.1016\/j.watres.2022.119532","article-title":"Effect of different co-foaming agents on PFAS removal from the environment by foam fractionation","volume":"230","author":"Buckley","year":"2023","journal-title":"Water Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"118085","DOI":"10.1016\/j.indcrop.2024.118085","article-title":"Protein enabled foam fractionation of anthocyanins from purple perilla leaves: Mechanisms, performance, and optimization","volume":"210","author":"Li","year":"2024","journal-title":"Ind. Crop Prod."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"137442","DOI":"10.1016\/j.colsurfa.2025.137442","article-title":"Amphiphilic Janus nanoparticle enabled aqueous two-phase flotation for separation and enrichment of rosmarinic acid from perilla leaves","volume":"724","author":"Li","year":"2025","journal-title":"Colloid. Surface. A"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"118060","DOI":"10.1016\/j.seppur.2020.118060","article-title":"Demulsification of crude oil\/water nanoemulsions stabilized by rhamnolipid biosurfactant using enzymes and pH-swing","volume":"259","author":"Onaizi","year":"2021","journal-title":"Sep. Purif. Technol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"146646","DOI":"10.1016\/j.jclepro.2025.146646","article-title":"Numerical and molecular dynamics simulation on the wetting-coating-aggregating behaviors of biomass and betaine-based surfactants in suppression coal dust pollution","volume":"525","author":"Ding","year":"2025","journal-title":"J. Clean. Prod."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"116633","DOI":"10.1016\/j.indcrop.2023.116633","article-title":"Foam fractionation of rosmarinic acid from perilla leaves using surface-modified Al2O3 nanoparticle as frother and collector","volume":"197","author":"Hu","year":"2023","journal-title":"Ind. Crop. Prod."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"125278","DOI":"10.1016\/j.molliq.2024.125278","article-title":"Foam fractionation of phenol using peanut meal protein: Mechanisms, performance, and optimization","volume":"407","author":"Hu","year":"2024","journal-title":"J. Mol. Liq."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"140291","DOI":"10.1016\/j.jhazmat.2025.140291","article-title":"Enhanced selective separation of mixed anionic and cationic dyes by whey soybean protein foam fractionation via a two-stage pH adjustment strategy","volume":"499","author":"Li","year":"2025","journal-title":"J. Hazard. Mater."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1590\/1678-457x.13516","article-title":"Optimization of ultrasound-assisted extraction of phenolic compounds, antioxidants and rosmarinic acid from perilla leaves using response surface methodology","volume":"36","author":"Li","year":"2016","journal-title":"Food Sci. Technol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"107351","DOI":"10.1016\/j.foodhyd.2021.107351","article-title":"Effects of combined treatment with ultrasound and pH shifting on foaming properties of chickpea protein isolate","volume":"124","author":"Wang","year":"2022","journal-title":"Food Hydrocoll."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2585","DOI":"10.1002\/jsfa.12291","article-title":"Foaming properties are improved by interactions between brewer\u2019s spent grain proteins and carrageenans in aqueous solution","volume":"103","author":"Drago","year":"2023","journal-title":"J. Sci. Food Agr."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"107409","DOI":"10.1016\/j.foodhyd.2021.107409","article-title":"Structure characteristics and functionality of water-soluble fraction from high-intensity ultrasound treated pea protein isolate","volume":"125","author":"Gao","year":"2022","journal-title":"Food Hydrocoll."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"120521","DOI":"10.1016\/j.indcrop.2025.120521","article-title":"High-efficiency separation of rosmarinic acid from perilla leaves by aqueous two-phase flotation using a protein carrier","volume":"225","author":"Li","year":"2025","journal-title":"Ind. Crop Prod."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"118185","DOI":"10.1016\/j.indcrop.2024.118185","article-title":"Use of Pine cone as bio-coagulant for heavy metal removal from industrial wastewater: Use of Box\u2013Behnken design","volume":"210","author":"Baatache","year":"2024","journal-title":"Ind. Crop Prod."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"112388","DOI":"10.1016\/j.lwt.2021.112388","article-title":"Effect of heterogeneous protein distribution on in situ pasting properties of black rice starch","volume":"153","author":"Chen","year":"2022","journal-title":"LWT-Food Sci. Technol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/j.foodhyd.2015.03.028","article-title":"Effect of hsian-tsao gum (HG) content upon rheological properties of film-forming solutions (FFS) and physical properties of soy protein\/hsian-tsao gum films","volume":"50","author":"Yang","year":"2015","journal-title":"Food Hydrocoll."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1016\/j.foodres.2015.08.024","article-title":"Study of the interactions between rosmarinic acid and bovine milk whey protein \u03b1-Lactalbumin, \u03b2-Lactoglobulin and Lactoferrin","volume":"77","author":"Ferraro","year":"2015","journal-title":"Food Res. Int."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"10515","DOI":"10.1021\/acs.jafc.1c01765","article-title":"Inhibition mechanism of \u03b1-amylase\/\u03b1-glucosidase by silibinin, its synergism with acarbose, and the effect of milk proteins","volume":"69","author":"Yang","year":"2021","journal-title":"J. Agr. Food Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"108584","DOI":"10.1016\/j.foodhyd.2023.108584","article-title":"Impact of pH on the interaction between soy whey protein and gum arabic at oil-water interface: Structural, emulsifying, and rheological properties","volume":"139","author":"Cao","year":"2023","journal-title":"Food Hydrocoll."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"112841","DOI":"10.1016\/j.jfoodeng.2025.112841","article-title":"Effect of protein\u2013polyphenol interactions on the structural and digestive properties of pork myofibrillar proteins","volume":"407","author":"Chen","year":"2025","journal-title":"J. Food Eng."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Wang, A., Fan, M., and Wu, L. (2026). Study on the Effects of Polyphenols on the Properties, Microstructure, and Digestibility of Rice Protein Gel and the Interaction Mechanisms Between Polyphenols and Rice Protein. Foods, 15.","DOI":"10.3390\/foods15111854"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.cep.2018.04.012","article-title":"Precipitation of proteins from soybean whey wastewater by successive foaming and defoaming","volume":"128","author":"Li","year":"2018","journal-title":"Chem. Eng. Process."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"120843","DOI":"10.1016\/j.jhazmat.2019.120843","article-title":"In-situ activated nanoparticle as an efficient and recyclable foam stabilizer for enhancing foam separation of LAS","volume":"379","author":"Hu","year":"2019","journal-title":"J. Hazard. Mater."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"132578","DOI":"10.1016\/j.seppur.2025.132578","article-title":"Enrichment and recovery of pea (Pisum sativum L.) proteins using foam fractionation for simultaneous enhancement of their functional properties","volume":"364","author":"Kumar","year":"2025","journal-title":"Sep. Purif. Technol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"113798","DOI":"10.1016\/j.foodres.2023.113798","article-title":"A novel strategy by combining foam fractionation with high-speed countercurrent chromatography for the rapid and efficient isolation of antioxidants and cytostatics from Camellia oleifera cake","volume":"176","author":"Li","year":"2024","journal-title":"Food Res. Int."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"127953","DOI":"10.1016\/j.seppur.2024.127953","article-title":"Foam fractionation for the separation and enrichment of trace m-phenylenediamine and o-phenylenediamine in solution","volume":"351","author":"Li","year":"2024","journal-title":"Sep. Purif. Technol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1016\/j.foodchem.2012.09.026","article-title":"Mechanistic and conformational studies on the interaction of food dye amaranth with human serum albumin by multispectroscopic methods","volume":"136","author":"Zhang","year":"2013","journal-title":"Food Chem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"8227","DOI":"10.1021\/acs.jafc.1c02526","article-title":"Mechanisms underlying the effect of tea extracts on in vitro digestion of wheat starch","volume":"69","author":"Li","year":"2021","journal-title":"J. Agr. Food Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/j.foodchem.2012.01.014","article-title":"Multispectroscopic studies on the interaction of maltol, a food additive, with bovine serum albumin","volume":"133","author":"Zhang","year":"2012","journal-title":"Food Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/j.jff.2018.07.022","article-title":"Exploring inhibitory mechanism of gallocatechin gallate on a-amylase and a-glucosidase relevant to postprandial hyperglycemia","volume":"48","author":"Wu","year":"2018","journal-title":"J. Funct. Foods."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"4739","DOI":"10.1007\/s11947-024-03372-6","article-title":"Integrated multi-spectroscopy and molecular dynamics simulations to explore the interaction mechanism of phenolic compounds and sea bass myofibrillar protein","volume":"17","author":"Zhu","year":"2024","journal-title":"Food Bioprocess Tech."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"100171","DOI":"10.1016\/j.focha.2022.100171","article-title":"Bioaccessibility of phenolic compounds in fresh and dehydrated blueberries (Vaccinium corymbosum L.)","volume":"2","year":"2023","journal-title":"Food Chem. Adv."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"119443","DOI":"10.1016\/j.fuel.2020.119443","article-title":"The synergistic role of silica nanoparticle and anionic surfactant on the static and dynamic CO2 foam stability for enhanced heavy oil recovery: An experimental study","volume":"287","author":"Zhao","year":"2021","journal-title":"Fuel."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1016\/j.cherd.2016.05.024","article-title":"Experimental study of nanoparticle-surfactant-stabilized CO2 foam: Stability and mobility control","volume":"111","author":"Farhadi","year":"2016","journal-title":"Chem. Eng. Res. Des."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"100582","DOI":"10.1016\/j.fochx.2023.100582","article-title":"Abalone visceral peptides containing cys and tyr exhibit strong in vitro anti-oxidant activity and cytoprotective effects against oxidative damage","volume":"17","author":"Liu","year":"2023","journal-title":"Food Chem. X."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Hussen, E.M., and Endalew, S.A. (2023). In vitro antioxidant and free-radical scavenging activities of polar leaf extracts of vernonia amygdalina. BMC Complement. Med., 23.","DOI":"10.1186\/s12906-023-03923-y"}],"container-title":["Foods"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2304-8158\/15\/14\/2525\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T04:27:17Z","timestamp":1784348837000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2304-8158\/15\/14\/2525"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,16]]},"references-count":46,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["foods15142525"],"URL":"https:\/\/doi.org\/10.3390\/foods15142525","relation":{},"ISSN":["2304-8158"],"issn-type":[{"value":"2304-8158","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,16]]}}}