Astragaloside IV attenuates cerebral ischemia‑reperfusion injury in rats through the inhibition of calcium‑sensing receptor‑mediated apoptosis

Abstract

cerebral ischemia-reperfusion injury (cIRI), caused by the reperfusion of blocked vessels following ischemic stroke, can lead to secondary brain injury. Throughout cIRI, apoptosis serves an important role. Astragaloside IV is a potential neuroprotectant that alleviates cIRI by inhibiting apoptosis. The calcium-sensing receptor (caSR) is a G-protein-coupled receptor, the activation of which aggravates ischemia-reperfusion injury. The aim of the present study was to investigate whether the protective effect of Astragaloside IV on cIRI may be associated with the regulation of caSR. A rat middle cerebral artery occlusion/reperfusion (McAO/R) model and an oxygen and glucose deprivation/reoxygenation (OGd/R) model of pheochromocytoma (Pc12) cells were used to study the neuronal injury induced by cIRI. Neurological function scores (NFS), 2,3,5-triphe-nylterazolium chloride and hematoxylin and eosin staining were used to determine brain damage in rats. cell viability was measured to evaluate the injury of OGd/R Pc12 cells. Western blotting was used to examine the expression of proteins associated with apoptosis and caSR. The caSR antagonist NPS-2143 and agonist Gdcl 3 were used to further confirm the effects of caSR during the process of apoptosis. The results demonstrated that Astragaloside IV alleviated cIRI by decreasing the NFS of rats, reducing the infarction volume of the brain and promoting the viability of Pc12 cells, as well as inhibiting the expression of cleaved caspase-3 and caSR, which was induced by cIRI. The results of the present study suggested that the activation of caSR may be involved in cIRI-induced brain damage in rats, and that Astragaloside IV may alleviate cIRI by inhibiting caSR activation-induced apoptosis.

Inhibition of Calcium-Sensing Receptor Alleviates Chronic Intermittent Hypoxia-Induced Cognitive Dysfunction via CaSR-PKC-ERK1/2 Pathway

“…To identify whether p-ERK1/2 held a critical function on IH-induced cell apoptosis and synaptic plasticity de cit, PD98059, a potent and selective MEK inhibitor, which can inhibit ERK1/2 signaling, was selected to pretreat PC12 cells. Firstly, according to previous research [24]. several different concentrations of inhibitors in our experiment were selected.…”

“…ERK1/2, as a subfamily of mitogen-activated protein kinases (MAPKs), is generally thought to be involved in cell apoptosis, proliferation and synaptic plasticity [21,22]. Further studies indicated that CaSR activation aggravates the apoptosis and the change of synaptic plasticity in hippocampal neurons during H/R [11,23] and the [Ca 2+ ]i overload induced by the activation of CaSR contributes to the apoptosis of PC12 cells in oxygen and glucose deprivation/reoxygenation [24]. However, it remains unclear whether CaSR holds a function on CIH-induced apoptosis and synaptic plasticity in hippocampal neurons by PKC-ERK1/2 signaling pathway.…”

NPS‐2143 inhibit glioma progression by suppressing autophagy through mediating AKT–mTOR pathway

“…The bioinformatics analysis results correspond with our findings. Additionally, Chun Wang and Shu‐Jin Du's studies demonstrated that NPS‐2143 had a neural protection effect in rat models, which suggests that NPS‐2143 might have the permeability of BBB 38,39 . However, we did not investigate the BBB permeability of NPS‐2143 in intracranial glioma mice mode.…”

Research Progress on the Ability of Astragaloside IV to Protect the Brain Against Ischemia-Reperfusion Injury

“…It has been found that during cerebral ischemia-reperfusion, the protein expression of CaSR and calcium influx increase. Astragaloside IV can inhibit the protein expression of CaSR after ischemia-reperfusion injury to reduce calcium reflux ( Du et al, 2021 ). Radix Astragali exerts a protective effect not only on neurons but also against ischemic apoptosis of neural stem cells.…”