LONDON / RankWire.AI / – Researchers at King’s College London have discovered a natural substance that enhanced key indicators of cardiac function in experimental models of heart failure with preserved ejection fraction, or HFpEF. Urolithin A improved some metrics by up to 80% in treated animals compared to untreated controls, helping the heart tissue relax, decreasing scarring, and limiting harmful enlargement of heart muscle cells. The team also observed improved relaxation in engineered human heart tissues derived 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, leading to symptoms like breathlessness, fatigue, and reduced exercise capacity. According to the British Heart Foundation, it accounts for roughly half of heart failure cases in the United Kingdom. Urolithin A forms in the body when gut bacteria process compounds found in foods including pomegranates, walnuts, and some berries, although its production can vary among individuals.
The research team found that urolithin A targets a protein called PKGIα, which plays a role in blood vessel regulation and heart muscle relaxation. The compound directly modified cysteine 42, a specific amino acid on the protein, activating a pathway linked to cardiovascular health. The study was published in Science Advances under the title “Targeting PKGIα Cys42 attenuates cardiac dysfunction in heart failure with preserved ejection fraction,” with researchers from King’s College London leading the work and Joseph Burgoyne serving as senior author.
Compound reduced fibrosis and abnormal heart enlargement
In the animal experiments, urolithin A improved diastolic function, which measures how effectively the heart relaxes and fills with blood, while also reducing fibrosis, the buildup of scar tissue that can impair normal cardiac performance. The treatment also lessened the enlargement of heart muscle cells compared with controls. The reported up to 80% improvement applied specifically to certain measures of heart function in the model, not in patients or in overall heart failure reduction.
The team further evaluated the compound using engineered human heart tissue created from stem cells, which replicate key features of human heart muscle and allow for measurement of contraction and relaxation under controlled conditions. Urolithin A enhanced both relaxation and contraction kinetics in this model. The researchers noted that urolithin A has already been studied in humans for other purposes and exhibited a favorable safety profile. However, the HFpEF findings were derived from animal models and engineered tissue, not clinical trials involving patients.
Human clinical evidence still needed
British Heart Foundation, which funded the research, indicated that the results offer early-stage evidence that urolithin A can enhance the heart’s ability to relax and fill between beats. The organization emphasized that these benefits have not yet been demonstrated in people with HFpEF, and King’s College London warned against interpreting the findings as proof that consuming pomegranates can treat heart failure. No single food has been shown in this study to prevent or cure the condition.
The findings pinpoint PKGIα cysteine 42 as a biological target for future HFpEF research and demonstrate how urolithin A activates this pathway in experimental systems. HFpEF remains a significant form of heart failure, often associated with conditions like high blood pressure, obesity, and diabetes. This study provides molecular insights into how heart relaxation might be influenced through this mechanism. However, clinical trials are necessary to assess whether urolithin A can safely produce similar effects in patients with HFpEF.