{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T20:58:13Z","timestamp":1784667493817,"version":"3.55.0"},"reference-count":127,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","award":["2019\/19988-2"],"award-info":[{"award-number":["2019\/19988-2"]}]},{"name":"Funda\u00e7\u00e3o Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","award":["2019\/19988-2"],"award-info":[{"award-number":["2019\/19988-2"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Cancer cachexia is a multifactorial syndrome characterized by metabolic dysregulation, inflammation, and progressive loss of skeletal muscle mass. Frequently observed in colorectal cancer patients, it is associated with poor clinical outcomes and reduced treatment tolerance. Current therapies provide limited benefit, underscoring the need for integrative approaches. Grape seed polyphenols, particularly oligomeric proanthocyanidins, have demonstrated potential to modulate catabolic signaling, mitochondrial dysfunction, and inflammatory responses involved in cachexia pathophysiology. This review integrates preclinical and clinical evidence on the use of grape seed-derived products, highlighting their effects on NF-\u03baB and AMPK pathways, redox homeostasis, and gut\u2013muscle axis. Furthermore, the nutritional composition and bioactive properties of grape seed flour\u2014rich in fiber and phenolic compounds\u2014are discussed in the context of nutraceutical applications. A clinical trial currently underway in Brazil aims to evaluate the effects of grape seed flour supplementation in colorectal cancer patients with cachexia. Altogether, grape-derived compounds offer a safe, low-cost, and mechanistically grounded strategy for improving nutritional status and resilience in oncological care.<\/jats:p>","DOI":"10.3390\/biology14091159","type":"journal-article","created":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T13:27:44Z","timestamp":1756733264000},"page":"1159","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Nutraceutical Interception of Cachexia: Grape-Derived Compounds as Pathophysiological Network Modulators"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-3845-0618","authenticated-orcid":false,"given":"Anderson Matheus Oliveira Haas","family":"Verdi","sequence":"first","affiliation":[{"name":"Postgraduate Program in Nutrition, Federal University of S\u00e3o Paulo (UNIFESP), Baixada Santista Campus, Santos 11015-020, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariana Lemos","family":"Rizzardi","sequence":"additional","affiliation":[{"name":"Postgraduate Program in Nutrition, Federal University of S\u00e3o Paulo (UNIFESP), Baixada Santista Campus, Santos 11015-020, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6990-7725","authenticated-orcid":false,"given":"Jaqueline Machado","family":"Soares","sequence":"additional","affiliation":[{"name":"Postgraduate Program in Community Development, Midwest State University (UNICENTRO), Irati Campus, Irati 11015-020, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0998-8161","authenticated-orcid":false,"given":"Dalton Luiz","family":"Schiessel","sequence":"additional","affiliation":[{"name":"Department of Nutrition, Midwest State University (UNICENTRO), CEDETEG Campus, Guarapuava 85040-167, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7373-1953","authenticated-orcid":false,"given":"Dario","family":"Coletti","sequence":"additional","affiliation":[{"name":"Unit of Histology and Medical Embryology, Department of Anatomy, Histology, Forensic Medicine and Orthopedics, Sapienza University of Rome, 00161 Roma, Italy"},{"name":"Biological Adaptation and Ageing (B2A), Institut de Biologie Paris-Seine, CNRS UMR 8256, Inserm U1164, Sorbonne Universit\u00e9, 75005 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marilia Cerqueira Leite","family":"Seelaender","sequence":"additional","affiliation":[{"name":"Cancer Metabolism Research Group, Department of Surgery and LIM 26-HCFMUSP, Faculty of Medicine, University of S\u00e3o Paulo, S\u00e3o Paulo 01246-903, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0427-0174","authenticated-orcid":false,"given":"Daniela Caetano","family":"Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Federal University of S\u00e3o Paulo (UNIFESP), Baixada Santista Campus, Santos 11015-020, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,1]]},"reference":[{"key":"ref_1","first-page":"394","article-title":"Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"68","author":"Bray","year":"2018","journal-title":"CA Cancer J. 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