{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T00:56:32Z","timestamp":1778806592362,"version":"3.51.4"},"reference-count":100,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T00:00:00Z","timestamp":1772236800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Zhejiang Provincial Natural Science Foundation of China","award":["LQ24H280009"],"award-info":[{"award-number":["LQ24H280009"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82204552"],"award-info":[{"award-number":["82204552"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004863","name":"Zhejiang Chinese Medical University","doi-asserted-by":"crossref","award":["2024RCZXZK19"],"award-info":[{"award-number":["2024RCZXZK19"]}],"id":[{"id":"10.13039\/501100004863","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Hedera helix (HE) contains diverse bioactive constituents, including triterpenoid saponins, flavonoids, and phenolic acids, which exhibit various pharmacological activities. In this study, ultrasound-assisted extraction (UAE) combined with natural deep eutectic solvent (NADES) was employed to enhance the extraction efficiency and elucidate the underlying mechanisms. Among the tested formulations, a ternary system composed of malonic acid (Mal), N,N\u2032-dimethylurea (DMU), and 1,4-butanediol (1,4-BDO) achieved the highest efficiency for extracting eight target compounds from the HE leaves. In addition, the key interactions among NADES components were confirmed by Fourier-transform infrared (FT-IR) spectroscopy, providing valuable insights into the extraction mechanism. The UAE process was systematically optimized through single-factor experiments. Subsequently, response surface methodology (RSM) identified the optimal conditions as ultrasonic time of 45 min, solid\/liquid ratio of 1:54 g\/mL, and ultrasonic temperature of 42 \u00b0C. Scanning electron microscopy (SEM) elucidated the microstructural alterations in plant cell walls induced by NADES-UAE, alongside the enhanced penetration and disruption mechanisms. In vitro bioactivity revealed that the NADES-extracted HE exerted strong inhibitory effect on HT-29 colon cancer cells. Overall, these findings demonstrate the high effectiveness and sustainability of NADES-UAE for extracting HE bioactive compounds and provide valuable implications for the industrial-scale production of plant-based functional products.<\/jats:p>","DOI":"10.3390\/ijms27052295","type":"journal-article","created":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T12:39:56Z","timestamp":1772455196000},"page":"2295","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Sustainable Extraction of Hedera helix Bioactive Compounds via Synergy of Natural Deep Eutectic Solvent and Ultrasound: Process Optimization, Mechanistic Insights and Anti-Colon Cancer Activity"],"prefix":"10.3390","volume":"27","author":[{"given":"Tangtang","family":"Li","sequence":"first","affiliation":[{"name":"School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 311402, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kai","family":"Hua","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 311402, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuya","family":"Ye","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 311402, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juzhao","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 311402, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongliang","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 311402, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yiming","family":"Sun","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 311402, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoxia","family":"Shen","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 311402, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qi","family":"Cui","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 311402, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.1600\/036364411X605100","article-title":"Phylogeny and biogeography of ivies (Hedera spp., Araliaceae), a polyploid complex of woody vines","volume":"36","author":"Green","year":"2011","journal-title":"Syst. 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