A compound produced by gut bacteria from pomegranate-derived molecules may play a critical role in protecting the cardiovascular system.
A compound created by gut bacteria from pomegranate-derived nutrients may help protect the arteries by reducing plaque buildup, easing inflammation, and making plaques less likely to rupture, according to researchers at Cardiff University.
In a study published in Antioxidants, scientists identified urolithin A as a key factor behind these effects. This molecule forms when gut microbes break down pomegranate polyphenols and shows strong cardiovascular benefits in preclinical models of atherosclerosis, the condition responsible for most heart attacks and strokes.
Pomegranates contain high levels of punicalagin, a polyphenol often associated with heart health. However, the body absorbs very little of this compound directly. Instead, gut bacteria convert it into smaller molecules called urolithins, which can circulate in the bloodstream and interact with tissues.
“Our findings show that the real biological effects come from what gut bacteria make from pomegranate compounds, rather than from the compounds in the fruit itself,” said Professor Dipak Ramji, senior author of the study and Professor of Cardiovascular Science at Cardiff University.
Cellular Evidence of Protective Effects
Researchers tested punicalagin, its intermediate form ellagic acid, and several urolithins in human immune and blood vessel cells grown in the lab. Urolithin A stood out, consistently reducing oxidative stress, lowering inflammatory gene activity, limiting immune cell movement, and decreasing cholesterol uptake by macrophages. These processes are central to the formation and growth of arterial plaques.
The team then evaluated urolithin A in LDL receptor-deficient mice fed a high-fat diet, a widely used model that resembles human atherosclerosis. After twelve weeks, treated mice developed smaller plaques with fewer inflammatory cells.
Plaques in these mice also showed higher levels of smooth muscle cells and collagen, both linked to stronger, more stable plaques that are less likely to rupture. Plaque rupture is the leading cause of heart attacks and strokes.
“What was striking is that these benefits occurred without lowering blood cholesterol levels,” Professor Ramji said. “This suggests urolithin A works by suppressing inflammation and stabilizing plaques, rather than by changing lipid levels.”
Broader Effects on Immunity and the Microbiome
The effects extended beyond the arteries. Mice given urolithin A had lower levels of circulating inflammatory monocytes and granulocytes, which are known to worsen atherosclerosis. At the same time, levels of beneficial short-chain fatty acids rose in blood and feces, suggesting positive shifts in gut microbial activity.
Further analysis using RNA-sequencing showed that urolithin A influenced hundreds of genes involved in inflammation, oxidative stress, and metabolism. Harmful pathways linked to atherosclerosis were reduced, while protective antioxidant and metabolic pathways became more active.
“These results help explain why diets rich in fruits like pomegranates are associated with cardiovascular benefits, but also why responses can vary between individuals,” Professor Ramji said. “Not everyone’s gut microbiome produces urolithin A efficiently.”
The researchers note that studies in humans are still needed to confirm these findings. If similar effects are seen, urolithin A could support existing heart disease treatments by targeting inflammation and improving plaque stability.
“This study opens the door to the use of urolithin A and microbiome‑driven strategies for cardiovascular disease prevention,” Professor Ramji said.
Reference: “Anti-Atherogenic Actions of Pomegranate Polyphenol Punicalagin and Its Metabolites: In Vitro Effects on Vascular Cells and In Vivo Atheroprotection by Urolithin A via Anti-Inflammatory and Plaque-Stabilising Mechanisms” by Sulaiman Alalawi, Daniah Rifqi, Alaa Alhamadi, Reem Alotibi, Fahad Alradi, Nouf Alshehri, Yee-Hung Chan, Jing Chen, Faizah Albalawi, Sarab Taha, Nabras Al-Mahrami, Irina A. Guschina, Timothy R. Hughes and Dipak P. Ramji, 19 April 2026, Antioxidants.
DOI: 10.3390/antiox15040507
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