Neuroprotective Effects of Four Phenylethanoid Glycosides on H2O2-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 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.

Total Glycosides of Cistanche deserticola Promote Neurological Function Recovery by Inducing Neurovascular Regeneration via Nrf-2/Keap-1 Pathway in MCAO/R Rats

“…As previously described (Jiang and Tu, 2009), TGs contain lots of bioactive compounds, for example echinacoside, tubuloside A, acteoside, isoacteoside and 2'-acetylacteoside, and some of them showed neuroprotective functions after cerebral I/R injury (Peng et al, 2016). Echinacoside has lots of pharmacological effects, such as antioxidation, anti-senescence, neuroprotection, anti-inflammation, promotion of cicatrization, hepatoprotection, promotion of bone formation and anti-tumor activities (Yu et al, 2016;Li et al, 2018;Ji et al, 2019;Xu et al, 2019). Recently, echinacoside has been identified as a potent antioxidant in the central nervous system (Lu et al, 2016).…”

Morin Protects Human Respiratory Cells from PM2.5 Induced Genotoxicity by Mitigating ROS and Reverting Altered miRNA Expression

“…Oxidative stress mediated Nrf2 pathway and inflammation related NFκB pathway would be the primary cellular response to any stress. Nrf2 had been the key transcription factor for the activation of antioxidant response elements and the production of antioxidant enzymes and cytoprotective enzymes [84]. While exposure to traffic PM 2.5 did not affect its expression significantly, morin pre-treatment reduced its expression (−14.42-fold).…”

Therapeutic potential of phenylethanoid glycosides: A systematic review

“…Verbascoside, isoverbascoside, salidroside, and echinacoside exhibited antioxidant and neuroprotective activities in hydrogen peroxide induced apoptosis in PC12 cells via the nuclear factor erythroid 2‐related pathway 87 . Caleolarioside B, paraboside B, and paraboside II isolated from Paraboea martinii effectively protected PC12 cells from H 2 O 2 ‐induced damage by upregulating HO‐1 88 .…”