Aims: Ginseng and ginsenosides are known for their remarkable effects on the central nervous system. However, pharmacokinetic studies have suggested that the Ginsenoside Rg1 (Rg1) cannot be efficiently transported through the blood-brain barrier. To investigate the effects of Rg1 in combination with mannitol protects neurons against glutamate-induced ER stress via the PERK-eIF2 -ATF4 signaling pathway.
Main methods: Rg1, along with the BBB permeabilizer mannitol, exhibited a potent neuroprotective effect by significantly reducing the neurological scores and infarct volume in rats exposed to middle cerebral artery occlusion. We evaluated the effect of Rg1 on neuroprotection after MCAO, and also explored its potential mechanism of action.
Key findings: Our results show that Rg1 reduced the number of terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive neurons. This neuroprotection may be dependent, at least in part, on the preservation of the endoplasmic reticulum and mitochondrial function. Ischemia-induced brain injury is largely caused by the excessive release of glutamate, which results in excitotoxicity and cell death. Neurons were pretreated with Rg1 before inducing endoplasmic reticulum stress with glutamate. A reduction in the expression of Bax and a concomitant increase in Bcl2 expression prevented the induction of apoptosis. Furthermore, Rg1 downregulated the expression of endoplasmic reticulum stress genes.
Significance: Our results indicate that Rg1 modulation of stress-responsive genes helps prevent glutamate-induced endoplasmic reticulum stress in neurons through the PERK-eIF2-α-ATF4 signaling pathway.
Keywords: Endoplasmic reticulum (ER) stress; Ginsenoside Rg1; Ischemic stroke; The blood–brain barrier.
Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.