{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T01:15:43Z","timestamp":1772759743569,"version":"3.50.1"},"reference-count":68,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,5,26]],"date-time":"2025-05-26T00:00:00Z","timestamp":1748217600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background: Venous hypertension is the primary cause of the disorder known as chronic venous insufficiency (CVI), which affects the lower extremities\u2019 venous system. Because of its biological proper ties, which include anti-inflammatory, antioxidant, and vascular tone enhancement, medicinal herbs and natural substances are highly recommended for treating CVI. Therefore, this study examined the advantages of a novel combination composed of hypersmin, pumpkin seed and amaranthus extracts (named MIX) in modulating different parameters involved with CVI. Methods: The capacity of these natural compounds to pass across the intestinal barrier and reach the bloodstream was examined using a 3D intestinal barrier model that mimics oral ingestion. The biological effects of the MIX were then compared to those of a commercial product using an in vitro CVI model. Results: The findings demonstrate that the new MIX significantly reduced inflammation while increasing nitric oxide production. The MIX was more successful than the commercial product in reducing apoptosis while restoring vasal tone and extracellular matrix activity. Conclusions: This work has therefore demonstrated the positive benefits of extracts from amaranthus, pumpkin seed and hypersmin in the context of CVI, raising the prospect of creating a unique combination for patients with CVI.<\/jats:p>","DOI":"10.3390\/nu17111807","type":"journal-article","created":{"date-parts":[[2025,5,27]],"date-time":"2025-05-27T03:34:46Z","timestamp":1748316886000},"page":"1807","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Analysis of the Combined Effects of a Novel Combination of Hypersmin, Pumpkin Seed and Amaranthus Extracts in an In Vitro Model of Chronic Venous Insufficiency"],"prefix":"10.3390","volume":"17","author":[{"given":"Sara","family":"Ferrari","sequence":"first","affiliation":[{"name":"Laboratory of Physiology, Department for Sustainable Development and Ecological Transition, 13100 Vercelli, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebecca","family":"Galla","sequence":"additional","affiliation":[{"name":"Noivita Srls, Spin Off University of Piemonte Orientale, Strada Privata Curti 7, 28100 Novara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simone","family":"Mul\u00e8","sequence":"additional","affiliation":[{"name":"Laboratory of Physiology, Department for Sustainable Development and Ecological Transition, 13100 Vercelli, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudio","family":"Molinari","sequence":"additional","affiliation":[{"name":"Laboratory of Physiology, Department for Sustainable Development and Ecological Transition, 13100 Vercelli, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5751-270X","authenticated-orcid":false,"given":"Francesca","family":"Uberti","sequence":"additional","affiliation":[{"name":"Laboratory of Physiology, Department for Sustainable Development and Ecological Transition, 13100 Vercelli, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1007\/s40119-021-00213-x","article-title":"Management of lower extremity pain from chronic venous insufficiency: A comprehensive review","volume":"10","author":"Orhurhu","year":"2021","journal-title":"Cardiol. 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