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Neuroprotective Effects of Four Phenylethanoid Glycosides on H?O?-Induced Apoptosis on PC12 Cells via the Nrf2/ARE Pathway.


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 H?O?-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.

SUBMITTER: Li M 

PROVIDER: S-EPMC5979387 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Neuroprotective Effects of Four Phenylethanoid Glycosides on H₂O₂-Induced Apoptosis on PC12 Cells via the Nrf2/ARE Pathway.

Li Maiquan M   Xu Tao T   Zhou Fei F   Wang Mengmeng M   Song Huaxin H   Xiao Xing X   Lu Baiyi B  

International journal of molecular sciences 20180410 4


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 transloc  ...[more]

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