LONDON / RankWire.AI / – Researchers at King’s College London have pinpointed a natural substance capable of improving key indicators of heart performance in laboratory models of heart failure with preserved ejection fraction, or HFpEF. Urolithin A boosted some measures by as much as 80% in treated animals relative to untreated controls. This compound also facilitated relaxation of cardiac tissue, diminished scarring, and curbed harmful enlargement of heart muscle cells. Additionally, scientists observed enhanced relaxation in engineered human heart tissues derived from stem cells.
HFpEF is characterized by the heart’s ability to pump normally or nearly so, while experiencing difficulty relaxing and filling properly between beats. Symptoms include breathlessness, fatigue, and limited exercise capacity. According to the British Heart Foundation, it accounts for roughly half of heart failure cases in the UK. Urolithin A forms in the body when gut bacteria process compounds present in foods such as pomegranates, walnuts, and certain berries, though its production varies among individuals.
The research team identified that urolithin A targets a protein called PKGIα, which plays a role in controlling blood vessel health and cardiac relaxation. The compound binds directly to cysteine 42, a specific amino acid on the protein, activating a pathway associated with cardiovascular function. The study, titled “Targeting PKGIα Cys42 attenuates cardiac dysfunction in heart failure with preserved ejection fraction,” was published in Science Advances. Led by scientists from King’s College London, with Joseph Burgoyne as senior author, the research sheds light on this molecular interaction.
Compound lessens fibrosis and prevents abnormal heart enlargement
In animal experiments, urolithin A enhanced diastolic function, which assesses how well the heart relaxes and fills with blood. Researchers observed a decrease in fibrosis, the formation of scar tissue that hampers normal cardiac function. The treatment also reduced the enlargement of heart muscle cells compared to controls. The reported 80% improvement pertains to specific measures within the experimental models, not directly to patient outcomes or overall heart failure reduction.
Further testing in engineered human heart tissue—created from stem cells—revealed that urolithin A improved both relaxation and contraction dynamics. These lab tissues mimic vital features of human heart muscle, allowing controlled measurement of function. The scientists noted that urolithin A has previously been studied in humans for other uses and exhibits a good safety profile. However, the current findings derive from animal models and engineered tissue, not clinical trials involving patients.
Human clinical data remains essential before conclusions can be drawn
British Heart Foundation, which funded the research, stated that these initial results suggest urolithin A could enhance heart tissue relaxation and filling. Nonetheless, they emphasized that benefits have not yet been demonstrated in individuals with HFpEF. Similarly, King’s College London cautioned against interpreting these findings as evidence that consuming pomegranates can treat heart failure. This study does not show that a single food can prevent or cure the condition.
The research highlights PKGIα cysteine 42 as a promising target for further investigation into HFpEF. It also illustrates how urolithin A activates this mechanism in experimental systems. HFpEF remains a prevalent type of heart failure, often co-occurring with high blood pressure, obesity, and diabetes. The study contributes molecular insights into how heart relaxation might be influenced via this pathway. Clinical trials involving humans are needed to determine whether urolithin A can safely induce similar effects in HFpEF patients.