Research Paper Volume 12, Issue 23 pp 23872—23888
Apigenin-7-O-β-D-(-6”-p-coumaroyl)-glucopyranoside treatment elicits a neuroprotective effect through GSK-3β phosphorylation-mediated Nrf2 activation
- 1 Department of Pharmacy, Xijing Hospital, The Fourth Military Medical School, Xi'an 710032, Shaanxi, China
- 2 Department of Anesthesiology and Perioperative Medicine, Xijing Hospital, The Fourth Military Medical School, Xi'an 710032, Shaanxi, China
- 3 The Medical Department of the Emergence Centre of Xi'an 718900, Shaanxi, China
- 4 Institute of Materia Medica, School of Pharmacy, The Fourth Military Medical School, Xi'an 710032, Shaanxi, China
- 5 Department of Psychiatry, Xijing Hospital, The Fourth Military Medical University, Xi’an 710032, Shaanxi Province, China
Received: February 28, 2020 Accepted: July 14, 2020 Published: November 18, 2020https://doi.org/10.18632/aging.104050
How to Cite
Copyright: © 2020 Zhang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
The current study was designed to seek the role of the glycogen synthase kinase-3β (GSK-β)-regulated NF-E2-related factor 2 (Nrf2) pathway in the antioxidant effect induced by Apigenin-7-O-β-D-(-6”-p-coumaroyl)-glucopyranoside (APG). Rat primary cultured cortical neurons were challenged by oxygen and glucose deprivation/reoxygenation (OGD/R) and then treated with APG. Cell viability, phosphorylation of GSK-β at Ser9 and nuclear expression of Nrf2 were measured. Male Sprague Dawley rats challenged by 2-h middle cerebral artery occlusion were treated with 50 mg/kg APG, and the neurological score, infarct volume, phosphorylation of GSK-3β and nuclear expression of Nrf2 were analyzed. The neuroprotective effect of APG and the expression levels of antioxidant enzymes and oxidative products were also examined in the presence and absence of Nrf2-siRNA and PI3K inhibitors. APG reduced the apoptotic proportion, attenuated LDH release and increased cell viability, and in vivo, APG improved neurological scores and reduced infarct volume. APG increased GSK-3β phosphorylation and Nrf2 nuclear translocation, while these effects were prevented by PI3K inhibitors or Nrf2-siRNA treatment in both OGD/R cell cultures and ischemic/reperfusion rats. These findings reveal that GSK-3β phosphorylation-mediated Nrf2 activation is involved in the neuroprotective effect of APG.