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cc-by (c) Mariano Nicola Llorente, et al., 2026
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/229739

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

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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.

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NICOLA LLORENTE, Mariano, et al. Distinctive Behavior and Selective Modulation of PPARγ by Pentacyclic Triterpenoid Pomolic Acid and Hederagenin from Rosa canina. Journal of Agricultural and Food Chemistry. 2026. ISSN 0021-8561. [consulted: 26 of June of 2026]. Available at: https://hdl.handle.net/2445/229739

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