Urolithins at physiological concentrations affect the levels of pro-inflammatory cytokines and growth factor in cultured cardiac cells in hyperglucidic conditions

• Urolithins may impact on the onset of diabetic cardiomyopathy.
• Physiological concentrations of urolithins may exert anti-inflammatory effects.
• Not all the urolithins were able to modify pro-inflammatory mediator expression.
• Urolithins underwent extensive metabolism in the applied cell models.

Diabetic cardiomyopathy (DCM) develops independently of common cardiovascular co-morbidities and is initiated by the metabolic derangements accompanying diabetes mellitus, including hyperglycaemia, which may cause a mild inflammatory state able to negatively affect myocardial biochemistry, structure, and function. This work shows how different urolithins, ellagitannin-derived metabolites, were able to modulate the pro-inflammatory mediators and growth factors secreted by rat cardiac myocytes and fibroblasts exposed to high glucose concentrations. At 1 µM concentration, coherent with dietary exposure to ellagitannin-rich foods, urolithins B and B-glucuronide succeeded in preventing inflammatory responses in cardiomyocytes, while in fibroblasts urolithin D was the most effective in controlling the overexpression of fractalkine, among the tested inflammatory mediators. Urolithins underwent extensive biotransformations in both cell types, including (de)glucuronidation, methylation, and sulphation. This suggests that the inflammatory bulk produced by hyperglycaemia could be attenuated by the regular intake of ellagitannin-rich foodstuffs such as pomegranates, raspberries, blackberries, strawberries, and walnuts.