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Peroxisome proliferator\u2010activated receptors (PPARs) are relevant to this emerging model because they regulate epithelial differentiation, inflammatory responses, mitochondrial metabolism, redox balance, and lipid\u2010mediator signaling. Impaired duodenal release of palmitoylethanolamide (PEA) provides direct translational evidence that defective PPAR\u03b1\u2010dependent lipid signaling may contribute to FD. Experimental studies further suggest that several plant\u2010derived bioactives modulate PPAR\u2010related pathways and other mechanisms involved in mucosal adaptation. Whether these effects restore duodenal function or improve clinically meaningful outcomes in humans remains uncertain. This review examines PPAR signaling as a mechanistic link between duodenal dysfunction and the actions of plant\u2010derived bioactives. Therefore, we distinguish disease\u2010specific evidence from findings obtained in other experimental settings and identify priorities for the development of mechanism\u2010based phytotherapy in FD.<\/jats:p>","DOI":"10.1002\/ptr.70449","type":"journal-article","created":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T01:54:43Z","timestamp":1789350883000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Plant\u2010Derived Bioactives and\n                    <scp>PPAR<\/scp>\n                    Signaling in Functional Dyspepsia: Mechanistic Insights and Therapeutic Perspectives"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5019-653X","authenticated-orcid":false,"given":"Irene","family":"Palenca","sequence":"first","affiliation":[{"name":"Neuropharmacology and Behavioral Science Laboratory IRCCS Fondazione Santa Lucia  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2101-1118","authenticated-orcid":false,"given":"Emidio","family":"Scarpellini","sequence":"additional","affiliation":[{"name":"Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases and Metabolism (CHROMETA) KU Leuven, Leuven, Belgium\u2010Internal Medicine Unit, Madonna del Soccorso General Hospital  San Benedetto del Tronto Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3206-6704","authenticated-orcid":false,"given":"Jan","family":"Tack","sequence":"additional","affiliation":[{"name":"Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases and Metabolism (CHROMETA)  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierluigi","family":"De Pierro","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine and Surgery University of Naples Federico II  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1467-1134","authenticated-orcid":false,"given":"Giovanni","family":"Sarnelli","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine and Surgery University of Naples Federico II  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8080-8218","authenticated-orcid":false,"given":"Giuseppe","family":"Esposito","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology \u201cV. 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