Abstract
Nuclear factor erythroid 2-related factor 2 (Nrf2) is a key transcription factor against oxidative stress and neurodegenerative disorders. Phenylethanoid glycosides (PhGs; salidroside, acteoside, isoacteoside, and echinacoside) exhibit antioxidant and neuroprotective bioactivities. This study was performed to investigate the neuroprotective effect and molecular mechanism of PhGs. PhGs pretreatment significantly suppressed H2O2-induced cytotoxicity in PC12 cells by triggering the nuclear translocation of Nrf2 and reversing the downregulated protein expression of heme oxygenase 1 (HO-1), NAD(P)H quinone oxidoreductase 1 (NQO1), glutamate cysteine ligase-catalytic subunit (GCLC), and glutamate-cysteine ligase modifier subunit (GCLM). Nrf2 siRNA or HO-1 inhibitor zinc protoporphyrin (ZnPP) reduced the neuroprotective effect. PhGs showed potential interaction with the Nrf2 binding site in Kelch-like ECH-association protein 1 (Keap1). This result may support the hypothesis that PhGs are activators of Nrf2. We demonstrated the potential binding between PhGs and the Keap1-activated Nrf2/ARE pathway, and that PhGs with more glycosides had enhanced effects.
Highlights
Oxidative stress, which is an imbalance of antioxidant homeostasis, induces lipid peroxidation, injury to protein and DNA, cell aging, and cell death
Pretreatment of cells with Phenylethanoid glycosides (PhGs) at 0.1, 1, 5, and 10 μg/mL had no effect on cell viability (Figure 1B) and markedly protected PC12 cells from H2O2-induced damage by improving the cell viability as 9.549–22.141%, 12.092–25.289%, 1.470–9.289%, and 3.411–11.441%, respectively (Figure 1C)
We investigated the neuroprotection of PhGs on H2O2 induced-cytotoxicity in PC12 cells
Summary
Oxidative stress, which is an imbalance of antioxidant homeostasis, induces lipid peroxidation, injury to protein and DNA, cell aging, and cell death. This process likely contributes to several neurodegenerative disorders, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and ischemia/reperfusion [1]. Therapeutic strategies for preventing oxidative stress-induced apoptosis may have the potential in neurodegenerative diseases treatment. Nuclear factor erythroid 2-related factor 2 (Nrf2), is a transcription factor that is strongly associated with oxidative stress. Activation of Nrf induces the transcription of numerous antioxidant and detoxification genes, including heme oxygenase-1 (HO-1), NAD(P)H quinine oxidoreductase 1
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