Astragalin alleviates ischemia/reperfusion‑induced brain injury via suppression of endoplasmic reticulum stress

Abstract

excessive apoptosis and neuronal dysfunction are pathological features of ischemic stroke. Previous studies have demonstrated that astragalin (aST) exerted both antiapoptotic and anti-inflammatory effects in several types of disease, although its potential effect in ischemic stroke remains unclear. The purpose of the present study was to investigate the effects of aST on cerebral ischemia/reperfusion (i/r)-induced brain injury and the underlying mechanisms. Brain injury was assessed in an experimental rat model using measurement of neurological scores and inflammatory factors. To assess the role of aST in i/r-induced brain injury and the potential mechanism of action, SH5Y were treated with thapsigargin and aST. apoptotic rate and er stress levels were measured by western blotting, reverse transcription-quantitative PCR and immunofluorescence staining. It was discovered that AST significantly improved long-term neurological outcomes in rats following cerebral i/r injury, through the attenuation of the expression levels of apoptotic proteins (Bax and cleaved-caspase-3) and the release of inflammatory cytokines, as well as upregulating the expression levels of the anti-apoptotic protein Bcl-2. Furthermore, aST attenuated the expression levels of the endoplasmic reticulum (er) stress-related protein, glucose-regulated protein, 78 kda, as well as its downstream apoptotic mediators (cHoP and caspase-12). Thapsigargin-induced er stress activation and apoptosis were also attenuated by aST in an in vitro neuronal cell culture model. in conclusion, these results suggested that aST may protect against i/r-induced brain injury, thus, highlighting its therapeutic potential in patients with ischemic stroke.

Mechanism of Endoplasmic Reticulum Stress in Cerebral Ischemia

“…For instance, astragalin, a kind of flavonoid, significantly attenuated the expression levels of apoptotic proteins (Bax and cleaved-caspase-3) and the release of inflammatory cytokines, as well as the ER-related proteins, glucose-regulated protein to alleviate I/R injury via suppression of ER stress on rats after transient middle cerebral artery occlusion (MCAO). Similar results were obtained in vitro neuronal cell culture model ( Liu et al, 2020 ). However, potential contamination, histological techniques, and methodological defects could be encountered in neuron cell culture technology ( Molcanyi et al, 2013 , 2014 ).…”

Tetramethylpyrazine alleviates endoplasmic reticulum stress‑activated apoptosis and related inflammation in chondrocytes

“…The current results demonstrated that TMP treatment decreased CHOP and GRP78 expression levels in cells exposed to IL-1β, suggesting a possible mechanism for TMP signaling. To optimize the investigation into the function of ER stress in OA, the present study used TG, which is known to induce ER stress in in vitro models ( 24 ). It was found that TMP exposure markedly decreased TG-triggered ER stress within chondrocytes.…”

“…Cells were incubated with TMP (100 µM) ( 22 , 23 ) at 37°C for 24 h in the presence or absence of TG (10 µM) ( 24 ). The concentrations of TMP and TG were mainly selected based on our preliminary experiments and previous reports as aforementioned.…”

Evaluation of Endothelial Dysfunction and Autophagy in Fibromyalgia-Related Vascular and Cerebral Cortical Changes and the Ameliorative Effect of Fisetin

“…Meanwhile, the exposure of a cell to external or internal stressor stimuli such as chronic hypoxia, low-grade inflammation [ 57 ], and oxidative stress lead to the accumulation of misfolded proteins and cellular damage [ 58 ]. In addition, ER stress can enhance mitochondrial stress and stimulate the apoptosis of the cerebral cells [ 59 ]. Additionally, it has been reported that ER stress is directly proportional to endothelial damage, apoptosis, and dysfunction [ 60 ].…”