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 (H2 O2 )-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 H2 O2 -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.

中文翻译：

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矮牵牛花素和番茄红素对过氧化氢作用的 H9c2 细胞的协同抗氧化作用：Akt/Nrf2 通路的作用

酚类和类胡萝卜素共存于水果和蔬菜中，食用后可产生相互作用。本研究旨在阐明花青素和类胡萝卜素之间抗氧化相互作用的可能机制，以矮牵牛素和番茄红素为例，在过氧化氢 (H2 O2) 诱导的心脏肌成纤维细胞 (H9c2) 细胞系模型中。结果表明，矮牵牛花素和番茄红素显示出抗氧化作用，而牵牛花素与番茄红素混合的比例较大，例如矮牵牛花素：番茄红素=9:1可显着防止细胞活力（8.98±1.03%）和细胞内抗氧化酶活性的丧失超氧化物歧化酶 (SOD, 27.07 ± 3.51%)、过氧化氢酶 (CAT, 29.51 ± 6.12%) 和谷胱甘肽过氧化物酶 (GSH-Px, 20.33 ± 2.65%)。而且，核因子红细胞2相关因子2（Nrf2）信号通路的NAD（P）H醌还原酶（NQO1）和血红素加氧酶（HO-1）的信使RNA（mRNA）和蛋白表达在矮牵牛花素、番茄红素中显着诱导和协同组合，表明抗氧化作用是通过激活 Nrf2 抗氧化反应途径。Nrf2 siRNA 进一步验证了这一点，矮牵牛花素显着诱导更多 NQO1 表达和番茄红素更多 HO-1 表达的结果表明，协同作用可能是两种化合物对 Nrf2 的这两个不同靶基因协同作用的结果。途径。这两种化合物还在协同组合中显着增加了 Akt 的磷酸化。本研究结果表明，矮牵牛花素和番茄红素在组合中比例较大时发挥协同抗氧化作用，有助于防止细胞氧化还原稳态，这可能为酚类和类胡萝卜素对心血管风险发挥有益作用提供理论基础. 实际应用：在这项研究中，我们揭示了矮牵牛花素和番茄红素的联合治疗抑制了 H2 O2 诱导的心肌细胞氧化损伤。此外，这些治疗有助于 Nrf2 通路和细胞氧化还原稳态的恢复，可能为酚类和类胡萝卜素对心血管风险发挥有益作用提供理论基础。