Investigating the cardioprotective potential of Punica granatum L. juice in a Caenorhabditis elegans model of atherosclerosis

Atherosclerotic cardiovascular disease is a leading age-related disorder and a major cause of morbidity and mortality worldwide. Its progression is driven by complex metabolic and inflammatory processes, yet effective interventions remain limited [ 1 ]. Emerging evidence suggests that dietary polyphenols play a crucial role in modulating key pathways associated with atherosclerosis [ 2 ]. Pomegranate juice (PGJ) is a rich source of polyphenolic compounds and has demonstrated various health benefits, including anti-inflammatory, neuroprotective, and stress-reducing effects. Additionally, it is considered a positive modulator of cardiovascular disease risk markers; however, its underlying mechanisms remain largely unexplored [ 3 ] [ 4 ]. This study aimed to develop a preclinical model of atherosclerosis-related metabolic dysfunction to investigate the potential of PGJ and its major constituent, punicalagin, in modulating metabolic healthspan and key energy-sensing pathways involved in disease progression. Caenorhabditis elegans serves as a powerful platform for studying lipid metabolism, oxidative stress responses, and longevity, making it an ideal system for cardiovascular research [ 4 ] [ 5 ]. Our findings reveal that PGJ significantly enhances metabolic healthspan by improving energy expenditure, reducing lipid accumulation, and increasing stress resilience to acute oxidative and thermal challenges. Additionally, pomegranate juice regulates key morphological parameters of C. elegans , suggesting broader effects on organismal physiology. Ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry analysis (UPLC-MS-qToF) identified punicalagin as the principal bioactive component, supporting its potential role in mediating these effects. These findings provide novel insights into its therapeutic potential of PGJ for cardiovascular health. Funding This research received funding from the Bulgarian National Science Fund (Contract number КП-06-КОСТ/11). Publication History Article published online: 05 March 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany