{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T08:49:20Z","timestamp":1791449360370,"version":"4.3.3"},"reference-count":48,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T00:00:00Z","timestamp":1785456000000},"content-version":"vor","delay-in-days":30,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["iubmb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["BioFactors"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>The gut\u2013brain axis is a key target in neuroinflammatory disorders. We investigated the protective effects of Mela Rosa Marchigiana pulp callus extract (MRME), a phytocomplex with a unique triterpenic profile. Using a validated transwell co\u2010culture model of the intestinal\u2010neural interface, differentiated Caco\u20102 cells formed a polarized epithelial barrier (apical), while BV2 microglia or SH\u2010SY5Y neurons were seeded in the basolateral compartment. Apical MRME pretreatment preserved Caco\u20102 barrier integrity against lipopolysaccharide or dextran sodium sulfate\u2010induced damage. MRME maintained occludin integrity and transepithelial electrical resistance (TEER), effectively neutralizing \u201cleaky gut\u201d\u2010like conditions. By stabilizing the barrier, MRME exerted indirect neuroprotection since high\u2010throughput live\u2010cell imaging revealed dose\u2010dependent reductions in reactive oxygen species generation and apoptosis (caspase\u20103\/7 activation) in both BV2 and SH\u2010SY5Y cells. MRME demonstrated a microbiologically neutral profile, exerting no inhibitory effects on either pathogenic or probiotic strains up to 10,000\u2009\u03bcg\/mL. MRME provides dual protection by strengthening the intestinal barrier and shielding the neural environment from systemic inflammation through host cellular modulation rather than microbial interference. These findings suggest MRME as a promising nutraceutical candidate for gut\u2013brain axis dysregulation.<\/jats:p>","DOI":"10.1002\/biof.70139","type":"journal-article","created":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T04:26:06Z","timestamp":1785558366000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pulp Callus Extract From\n                    <i>Malus domestica<\/i>\n                    var. Mela Rosa Marchigiana Preserves Intestinal Barrier Integrity and Confers Neuroprotection in a Gut\u2013Brain Axis Co\u2010Culture Model"],"prefix":"10.1002","volume":"52","author":[{"given":"Alessandro","family":"Nicois","sequence":"first","affiliation":[{"name":"Department of Biomolecular Sciences University of Urbino Carlo Bo  Urbino Italy"},{"name":"Institute of Biomolecular Chemistry National Research Council of Italy  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniele","family":"Fraternale","sequence":"additional","affiliation":[{"name":"Department of Biomolecular Sciences University of Urbino Carlo Bo  Urbino Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Palma","sequence":"additional","affiliation":[{"name":"Department of Biomolecular Sciences University of Urbino Carlo Bo  Urbino 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Biomolecular Sciences University of Urbino Carlo Bo  Urbino Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Di Giacomo","sequence":"additional","affiliation":[{"name":"Department of Biomolecular Sciences University of Urbino Carlo Bo  Urbino Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigia","family":"Cristino","sequence":"additional","affiliation":[{"name":"Institute of Biomolecular Chemistry National Research Council of Italy  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzo","family":"Di Marzo","sequence":"additional","affiliation":[{"name":"Institute of Biomolecular Chemistry National Research Council of Italy  Naples Italy"},{"name":"Canada Excellence Research Chair on the Microbiome\u2010Endocannabinoidome Axis in Metabolic Health, Department of Medicine and School of Nutrition Universit\u00e9 Laval  Qu\u00e9bec City Qu\u00e9bec Canada"},{"name":"Institut Universitaire de Cardiologie et de Pneumologie de Qu\u00e9bec Universit\u00e9 Laval  Qu\u00e9bec City Qu\u00e9bec Canada"},{"name":"Centre Nutrition, sant\u00e9 et soci\u00e9t\u00e9 (NUTRISS), INAF, \u00c9cole de Nutrition Universit\u00e9 Laval  Qu\u00e9bec City Qu\u00e9bec Canada"},{"name":"Joint International Research Unit Between Universit\u00e9 Laval and National Research Council on Chemical and Biomolecular Studies on the Microbiome and Its Impact on Metabolic Health and Nutrition (JIRU\u2010MicroMeNu) Universit\u00e9 Laval  Qu\u00e9bec City Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Cristina","family":"Albertini","sequence":"additional","affiliation":[{"name":"Department of Biomolecular Sciences University of Urbino Carlo Bo  Urbino Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Letizia","family":"Palomba","sequence":"additional","affiliation":[{"name":"Department of Biomolecular Sciences University of Urbino Carlo Bo  Urbino 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