LONDON / RankWire.AI / – Researchers at King’s College London have identified a natural compound that improved key measures of heart function in experimental models of heart failure with preserved ejection fraction, or HFpEF. Urolithin A improved some measures by up to 80% in treated animal models compared with untreated controls. The compound also helped heart tissue relax, reduced scarring and limited harmful enlargement of heart muscle cells. Researchers also recorded improved relaxation in engineered human heart tissue made from stem cells.
HFpEF occurs when the heart maintains a normal or near-normal pumping fraction but struggles to relax and fill properly between beats. The condition can cause breathlessness, fatigue and reduced ability to exercise. It accounts for roughly half of heart failure cases in the United Kingdom, according to the British Heart Foundation. Urolithin A forms in the body when gut bacteria process compounds found in foods including pomegranates, walnuts and some berries, although production can vary among individuals.
The research team found that urolithin A acts on a protein called PKGIα, which helps regulate blood vessel function and heart muscle relaxation. The compound directly modified cysteine 42, a specific amino acid on the protein, and activated a pathway linked to cardiovascular function. Science Advances published the study under the title “Targeting PKGIα Cys42 attenuates cardiac dysfunction in heart failure with preserved ejection fraction.” Researchers from King’s College London led the work, with Joseph Burgoyne serving as senior author.
Compound reduced fibrosis and abnormal heart enlargement
In the animal model, urolithin A improved diastolic function, which measures how effectively the heart relaxes and fills with blood. Researchers also found less fibrosis, the buildup of scar tissue that can interfere with normal cardiac performance. Treatment reduced enlargement of heart muscle cells compared with untreated controls. The reported improvement of up to 80% applied to specific measures of heart function in the experimental model. It did not represent an 80% improvement in patients or an 80% reduction in heart failure.
The team also tested the compound in engineered human heart tissue created from stem cells. These laboratory tissues reproduce important features of human heart muscle and allow researchers to measure contraction and relaxation under controlled conditions. Urolithin A improved both relaxation and contraction kinetics in that model. The researchers noted that urolithin A has already undergone studies in humans for other purposes and has shown a favorable safety profile. The HFpEF findings, however, came from animals and engineered tissue rather than clinical trials involving patients.
Clinical evidence in heart failure patients remains necessary
The British Heart Foundation, which funded the study, said the results provide early-stage evidence that urolithin A can improve the ability of heart tissue to relax and fill between beats. The organization also stressed that researchers have not yet demonstrated those benefits in people with HFpEF. King’s College London similarly cautioned against treating the findings as evidence that eating pomegranates can treat heart failure. No single food has been shown by this study to prevent or treat the condition.
The findings identify PKGIα cysteine 42 as a biological target for further HFpEF research and show how urolithin A activates that mechanism in experimental systems. HFpEF remains a major form of heart failure and often occurs alongside conditions such as high blood pressure, obesity and diabetes. The study adds molecular evidence about how heart relaxation may be influenced through this pathway. Clinical trials in people would be required to determine whether urolithin A can safely produce similar effects in patients with HFpEF.