Pomegranate‐Derived Polyphenols Reduce Reactive Oxygen Species Production via SIRT3‐Mediated SOD2 Activation

Pomegranate‐derived polyphenols are expected to prevent life‐style related diseases. In this study, we evaluated the ability of 8 pomegranate‐derived polyphenols, along with other polyphenols, to augment SIRT3, a mammalian SIR2 homolog localized in mitochondria. We established a system for screening foods/food ingredients that augment the SIRT3 promoter in Caco‐2 cells and identified 3 SIRT3‐augmenting pomegranate‐derived polyphenols (eucalbanin B, pomegraniin A, and eucarpanin T1). Among them, pomegraniin A activated superoxide dismutase 2 (SOD2) through SIRT3‐mediated deacetylation, thereby reducing intracellular reactive oxygen species. The other SIRT3‐augmenting polyphenols tested also activated SOD2, suggesting antioxidant activity. Our findings clarify the underlying mechanisms involved in the antioxidant activity of pomegraniin A.