Plant‐Derived Bioactives and PPAR Signaling in Functional Dyspepsia: Mechanistic Insights and Therapeutic Perspectives

Abstract

ABSTRACT Functional dyspepsia (FD) is a common disorder of gut‐brain interaction in which gastric sensorimotor abnormalities may coexist with impaired duodenal barrier function, low‐grade immune activation, and altered neuroimmune signaling. Peroxisome proliferator‐activated receptors (PPARs) are relevant to this emerging model because they regulate epithelial differentiation, inflammatory responses, mitochondrial metabolism, redox balance, and lipid‐mediator signaling. Impaired duodenal release of palmitoylethanolamide (PEA) provides direct translational evidence that defective PPARα‐dependent lipid signaling may contribute to FD. Experimental studies further suggest that several plant‐derived bioactives modulate PPAR‐related 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‐derived bioactives. Therefore, we distinguish disease‐specific evidence from findings obtained in other experimental settings and identify priorities for the development of mechanism‐based phytotherapy in FD.