{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T11:09:03Z","timestamp":1787656143405,"version":"build-2736575974"},"reference-count":84,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T00:00:00Z","timestamp":1761523200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004410","name":"The Scientific and Technological Research Council of T\u00fcrkiye","doi-asserted-by":"crossref","award":["1919B012303375"],"award-info":[{"award-number":["1919B012303375"]}],"id":[{"id":"10.13039\/501100004410","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The green husk of Juglans regia L. is rich in bioactive phytochemicals and exhibits various biological activities. This study aimed to investigate the skin anti-aging potential of the green husk of J. regia by determining the optimal extraction conditions using a Box\u2013Behnken Design (BBD), targeting elastase inhibition, and by correlating variations in phenolic compounds identified through metabolomic analyses with changes in the extraction conditions. Ultrasonic-assisted extraction was employed along with natural deep eutectic solvents (NADES). Three levels of three independent variables (NADES\/H2O ratio, temperature, and extraction time) were incorporated into the BBD. Phenolic compounds were determined semi-quantitatively using liquid chromatography\u2013quadrupole time-of-flight mass spectrometry (LC-q-TOF\/MS), while elastase inhibition was evaluated by spectroscopic methods. Quadratic response surface models were proposed based on the BBD model adequacy test using multiple regression analysis. It was determined that the optimum conditions for maximizing phenolic content and elastase inhibition were 99.79% ethanol, 51.30 \u00b0C temperature, and 49.58 min, in which case the desirability score was 1. Metabolomic analysis identified 41 phenolic compounds across 27 ontological groups, with 24 compounds showing a semi-quantitative increase. Consequently, the waste green husk of J. regia demonstrated enhanced anti-aging potential due to the higher content and diversity of phenolic compounds.<\/jats:p>","DOI":"10.3390\/molecules30214191","type":"journal-article","created":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T02:23:28Z","timestamp":1761704608000},"page":"4191","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Metabolomic Profiling, Box\u2013Behnken Design-Based Optimization of Ultrasonic Extraction, and Skin Anti-Aging Potential of the Green Husk of Juglans regia L. as a Sustainable Natural Waste"],"prefix":"10.3390","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7679-7165","authenticated-orcid":false,"given":"S\u0131la \u00d6zlem","family":"\u015eener","sequence":"first","affiliation":[{"name":"Department of Pharmacognosy, Gulhane Faculty of Pharmacy, University of Health Sciences, 06210 Ankara, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-9854-782X","authenticated-orcid":false,"given":"Sabita","family":"Shaha","sequence":"additional","affiliation":[{"name":"School of Pharmacy and Medical Sciences, University of Bradford, Bradford BD7 1AZ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sahar Sadigh","family":"Barazandeh","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy, Gulhane Faculty of Pharmacy, University of Health Sciences, 06210 Ankara, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-1611-288X","authenticated-orcid":false,"given":"\u00d6mer","family":"\u015een","sequence":"additional","affiliation":[{"name":"Department of Basic Sciences and Health, Hemp Research Institute, Yozgat Bozok University, 66900 Yozgat, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1076-1300","authenticated-orcid":false,"given":"Engin","family":"Ko\u00e7ak","sequence":"additional","affiliation":[{"name":"Department of Analytical Chemistry, Gulhane Faculty of Pharmacy, University of Health Sciences, 06210 Ankara, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0956-6567","authenticated-orcid":false,"given":"Tu\u011fba","family":"Suba\u015f","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy, Faculty of Pharmacy, Karadeniz Technical University, 61080 Trabzon, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u015eerife Nur","family":"K\u0131ra\u00e7","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy, Gulhane Faculty of Pharmacy, University of Health Sciences, 06210 Ankara, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7337-6215","authenticated-orcid":false,"given":"Emirhan","family":"Nemutlu","sequence":"additional","affiliation":[{"name":"Department of Analytical Chemistry, Faculty of Pharmacy, Hacettepe University, 06800 Ankara, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,27]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2025, October 21). 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