Distinctive Behavior and Selective Modulation of PPARγ by Pentacyclic Triterpenoid Pomolic Acid and Hederagenin from Rosa canina

  • J Agric Food Chem. 2026 May 13;74(18):14376-14392. doi: 10.1021/acs.jafc.5c17657.
Mariano Nicola-Llorente  1  2 ,  Francisco J Hermoso-Pinilla  1  3 ,  Daniel Torres-Oteros  1  2 ,  F Javier Luque  1  3  4 ,  Silvia Canudas  1  2 ,  Pedro F Marrero  1  3  5 ,  Diego Haro  1  3  5 ,  Joana Relat  1  2  5
Affiliations
  • 1. Department of Nutrition, Food Sciences and Gastronomy, School of Pharmacy and Food Sciences, Food Torribera Campus, University of Barcelona, Santa Coloma de Gramenet 08921, Spain.
  • 2. Institute of Nutrition and Food Safety of the University of Barcelona (INSA-UB), Maria de Maeztu Unit of Excellence, Santa Coloma de Gramenet 08921, Spain.
  • 3. Institute of Biomedicine of the University of Barcelona (IBUB), Barcelona 08028, Spain.
  • 4. Institute of Theoretical and Computational Chemistry (IQTCUB). Barcelona 08028, Spain.
  • 5. Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid 28029, Spain.
PMID: 42057314 DOI: 10.1021/acs.jafc.5c17657
Abstract

Bioactive triterpenoids present in plant-derived foods are emerging as modulators of metabolic health, although their molecular targets and mechanisms remain unclear. In this study, we characterize Pomolic acid and Hederagenin, two Pentacyclic Triterpenoids from Rosa canina, as antagonists and selective modulators of Peroxisome Proliferator-activated Receptor gamma (PPARγ). Both compounds reduced lipid accumulation during 3T3-L1 adipocyte differentiation and antagonized rosiglitazone-induced PPARγ transactivation without intrinsic agonist activity. Pomolic acid behaved as a neutral antagonist, repressing adipogenic and lipogenic gene expression and preventing TRAP220 recruitment. In contrast, Hederagenin selectively modulated PPARγ target genes involved in lipid handling while limiting triglyceride accumulation. TR-FRET assays confirmed direct binding to the receptor, and molecular dynamics simulations revealed a betulinic acid─like binding mode that destabilizes helices H11-H12 and disrupts the AF-2 coactivator interface. These findings provide mechanistic insight into how structurally related dietary triterpenoids modulate PPARγ signaling and support them as candidates for Metabolic Disease strategies.

Keywords
Rosa canina; TR-FRET binding assays; adipogenesis; antagonists; food bioactives; functional foods; hederagenin; lipid metabolism; molecular docking and dynamics; pentacyclic triterpenoids; pomolic acid; selective PPARγ modulators.
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