Synergistic antioxidant effects of petunidin and lycopene in H9c2 cells submitted to hydrogen peroxide: Role of Akt/Nrf2 pathway

Phenolics and carotenoids coexist in fruits and vegetables and could possess interaction effects after consumption. The present study aims to elucidate the possible mechanisms of the antioxidant interactions between anthocyanins and carotenoids using petunidin and lycopene as examples in hydrogen peroxide (H₂O₂)‐induced heart myofibroblast cell (H9c2) line model. The results revealed that petunidin and lycopene showed antioxidant effects and petunidin in a larger proportion mixed with lycopene, for example, petunidin: lycopene = 9:1 significantly protected against the loss of the cell viability (8.98 ± 1.03%) and intracellular antioxidant enzyme activities of superoxide dismutase (SOD, 27.07 ± 3.51%), catalase (CAT, 29.51 ± 6.12%), and glutathione peroxidase (GSH‐Px, 20.33 ± 2.65%). Moreover, the messenger RNA (mRNA) and protein expressions of NAD(P)H quinone reductase (NQO1) and heme oxygenase (HO‐1) of the nuclear factor erythrocyte 2‐related factor 2 (Nrf2) signaling pathway were significantly induced in petunidin, lycopene, and synergistic combinations, suggesting that the antioxidant action was through activating the Nrf2 antioxidant response pathway. This was further validated by Nrf2 siRNA, and the results that petunidin significantly induced more of NQO1 expression and lycopene more of HO‐1 suggested that the synergism may be a result of concerted actions by the two compounds on these two different target genes of the Nrf2 pathway. The two compounds also significantly increased the phosphorylation of Akt in synergistic combinations. Findings of the present study demonstrated that petunidin and lycopene exerted synergistic antioxidant effects when petunidin in a larger proportion in the combinations and contribute to the prevention of cellular redox homeostasis, which might provide a theoretical basis for phenolics and carotenoids playing beneficial effects on the cardiovascular risk. PRACTICAL APPLICATION: In this study, we revealed that the combined treatments of petunidin and lycopen inhibited H₂O₂‐induced oxidative damage in myocardial cells. Moreover, the treatments contributed to the Nrf2 pathway and the restoration of cellular redox homeostasis might provide a theoretical basis for phenolics and carotenoids playing beneficial effects on the cardiovascular risk.