Metabolic Rewiring by Pomegranate Juice and Punicalagin Is Associated with NHR-49/MDT-15-Related Responses and Enhanced Stress Resilience
5 affiliations
- 1Laboratory of Metabolomics, Institute of Microbiology, Bulgarian Academy of Sciences, 4000 Plovdiv, Bulgaria
- 2Department of Plant Cell Biotechnology, Center of Plant Systems Biology and Biotechnology, 4023 Plovdiv, Bulgaria
- 3Department of Physiology, Medical School, National and Kapodistrian University of Athens, 115 27 Athens, Greece
- 4Department of Plant Metabolomics, Center of Plant Systems Biology and Biotechnology, 4023 Plovdiv, Bulgaria
- 5Department of Biology, University of Western Ontario, London, ON N6A 5B7, Canada
Abstract
Metabolic homeostasis is a key determinant of stress resilience and healthy ageing. Pomegranate juice (PGJ) and its characteristic ellagitannin punicalagin (PUN) have been associated with beneficial metabolic effects, but the mechanisms through which they influence metabolic adaptation and healthspan, and whether they act through shared or distinct pathways, remain poorly defined. We investigated the effects of lyophilized PGJ (50, 100, and 200 μg/mL) and PUN (25, 50, and 100 μM) on metabolic regulation and stress resilience in Caenorhabditis elegans. Nuclear magnetic resonance spectroscopy was employed for metabolic profiling of PGJ, whereas ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry enabled the quantification of PUN at 2.4 ± 0.127 µg/mg lyophilized juice. Under glucose-enriched conditions, PGJ (200 μg/mL) and PUN (100 μM) reduced normalised Nile Red fluorescence to 0.53 and 0.59 of vehicle levels. On day 10 of adulthood, both treatments increased mean survival under oxidative stress by 1.73- and 1.50-fold, respectively. Both treatments increased MDT-15 reporter response (1.13- and 1.44-fold, respectively), whereas PGJ preferentially increased AAK-2- and FAT-6-associated responses and PUN elevated NHR-49- and FAT-7 expression. PUN also improved locomotor performance under amyloid-β-induced proteotoxic stress. Overall, PGJ and PUN elicited partially overlapping metabolic responses in C. elegans, with NHR-49 and MDT-15 emerging as treatment-responsive regulators associated with lipid homeostasis.
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BibTeX
@article{todorova2026metabolic,
title = {{Metabolic Rewiring by Pomegranate Juice and Punicalagin Is Associated with NHR-49/MDT-15-Related Responses and Enhanced Stress Resilience}},
author = {Monika N. Todorova and Biser K. Binev and Christina Ploumi and Eleni Tsakiri and Antonis Roussos and Dimitre A. Ivanov and Martina S. Savova and Konstantinos Palikaras and Milen I. Georgiev},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = nov,
doi = {10.3390/ijms27219852},
url = {https://www.mdpi.com/1422-0067/27/21/9852},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Metabolic Rewiring by Pomegranate Juice and Punicalagin Is Associated with NHR-49/MDT-15-Related Responses and Enhanced Stress Resilience
AU - Monika N. Todorova
AU - Biser K. Binev
AU - Christina Ploumi
AU - Eleni Tsakiri
AU - Antonis Roussos
AU - Dimitre A. Ivanov
AU - Martina S. Savova
AU - Konstantinos Palikaras
AU - Milen I. Georgiev
PY - 2026
DA - 2026/11/03
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27219852
UR - https://www.mdpi.com/1422-0067/27/21/9852
AB - Metabolic homeostasis is a key determinant of stress resilience and healthy ageing. Pomegranate juice (PGJ) and its characteristic ellagitannin punicalagin (PUN) have been associated with beneficial metabolic effects, but the mechanisms through which they influence metabolic adaptation and healthspan, and whether they act through shared or distinct pathways, remain poorly defined. We investigated the effects of lyophilized PGJ (50, 100, and 200 μg/mL) and PUN (25, 50, and 100 μM) on metabolic regulation and stress resilience in Caenorhabditis elegans. Nuclear magnetic resonance spectroscopy was employed for metabolic profiling of PGJ, whereas ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry enabled the quantification of PUN at 2.4 ± 0.127 µg/mg lyophilized juice. Under glucose-enriched conditions, PGJ (200 μg/mL) and PUN (100 μM) reduced normalised Nile Red fluorescence to 0.53 and 0.59 of vehicle levels. On day 10 of adulthood, both treatments increased mean survival under oxidative stress by 1.73- and 1.50-fold, respectively. Both treatments increased MDT-15 reporter response (1.13- and 1.44-fold, respectively), whereas PGJ preferentially increased AAK-2- and FAT-6-associated responses and PUN elevated NHR-49- and FAT-7 expression. PUN also improved locomotor performance under amyloid-β-induced proteotoxic stress. Overall, PGJ and PUN elicited partially overlapping metabolic responses in C. elegans, with NHR-49 and MDT-15 emerging as treatment-responsive regulators associated with lipid homeostasis.
SN - 1422-0067
ER -