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Hyperoside attenuates hydrogen peroxide-induced L02 cell damage via MAPK-dependent Keap₁–Nrf₂–ARE signaling pathway

Xing, Hai-Yan, Liu, Yao, Chen, Jian-Hong, Sun, Feng-Jun, Shi, Hui-Qing, Xia, Pei-Yuan
Biochemical and biophysical research communications 2011 v.410 no.4 pp. 759-765
Western blotting, antioxidant activity, antioxidants, catalase, dose response, flavonoids, fluorescent antibody technique, glutathione peroxidase, heme oxygenase (biliverdin-producing), hydrogen peroxide, lactate dehydrogenase, membrane potential, mitochondrial membrane, mitogen-activated protein kinase, oxidative stress, quantitative polymerase chain reaction, signal transduction, superoxide dismutase, transcription factors
The flavonoid hyperoside has been reported to elicit cytoprotection against oxidative stress partly by increasing the activity of antioxidant enzymes, such as glutathione peroxidase, superoxide dismutase and catalase. However, the cellular and molecular mechanisms underlying this effect remain unclear. Here, hepatic L02 cells exposed to H₂O₂ (100μM) were used to demonstrate that hyperoside protected cells by significantly inhibiting overproduction of intracellular ROS, depletion of the mitochondrial membrane potential and leakage of lactate dehydrogenase. Hyperoside further enhanced the cellular antioxidant defense system through increasing the activity of heme oxygenase-1 (HO-1), and by up-regulating HO-1 expression. Meanwhile, real time PCR, western blot and immunofluorescence studies revealed that hyperoside stimulated nuclear translocation of the Nrf₂ transcription factor in a dose-dependent manner, and this effect was significantly suppressed by pharmacological inhibition of the mitogen-activated protein kinases (MAPK) p38 and ERK. Collectively, our data provide the first description of the mechanism underlying hyperoside’s ability to attenuate H₂O₂-induced cell damage, namely this compound interacts with the MAPK-dependent Keap₁–Nrf₂–ARE signaling pathway to up-regulate HO-1 expression and enhance intracellular antioxidant activity.