astragalin and Brain-Ischemia

Astragalin (AG), a flavonoid from many traditional herbs and medicinal plants, has been described to exhibit in vitro anti-inflammatory activity. The paper aimed to study the effects of astragalin on anti-inflammatory, anti-oxidative ability and apoptosis signaling pathway in brain tissue of rats with cerebral ischemia-reperfusion injury, and to explore its possible mechanism.. The rat model of focal cerebral ischemia-reperfusion injury was established by suture method. It was randomly divided into 5 groups, sham operation group, ischemia-reperfusion (I/R) treatment group, and astragalin treatment I / R group (12.5, 25, 50 mg / kg). After 24 h of reperfusion, the neurological deficits of the rats were analyzed and HE staining was performed. The volume of cerebral infarction was calculated by triphenyltetrazolium chloride (TTC) staining, and the apoptosis of nerve cells was detected by TUNEL staining. In addition, the content of malondialdehyde (MDA), nitric oxide (NO), superoxide dismutase (SOD), glutathione (GSH) assay and glutathione peroxidase (GSH-Px) were measured in rat brain tissue. Western blot analysis was used to determine the expression of related proteins.. Compared with I/R group, the neurological deficit score and infarct volume of I/R rats were reduced in the astragalin treatment group. In the astragalin treatment group, MDA and NO levels in I/R rats were reduced, antioxidant enzymes and superoxide dismutase (SOD) activity were increased. In the astragalin treatment group, NF-κB (p65) and cyclooxygenase-2 (COX-2) expression levels were down-regulated, NF-E2-related factor 2 (Nrf2) nucleus and heme oxygenase-1 (HO-1) protein expression levels were up-regulated. In addition, the astragalin treatment can inhibit apoptosis, down-regulate Bax and cleaved caspase-3 expression, up-regulate Bcl-Xl expression.. The antioxidant properties of astragalin may play an important role in improving cerebral ischemia-reperfusion injury.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Apoptosis; Brain Ischemia; Kaempferols; Male; Rats; Rats, Sprague-Dawley; Reperfusion Injury

Excessive apoptosis and neuronal dysfunction are pathological features of ischemic stroke. Previous studies have demonstrated that astragalin (AST) exerted both anti‑​apoptotic 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.

Topics: Animals; Apoptosis; bcl-2-Associated X Protein; Brain Ischemia; Caspase 3; Cell Line; Disease Models, Animal; Endoplasmic Reticulum Stress; Gene Expression Regulation; Kaempferols; Male; Proto-Oncogene Proteins c-bcl-2; Rats; Reperfusion Injury

To study the effects of astragalan (AG) on the expression of the neural cell adhesion molecule(NCAM) and c-fos of hippocampus CA1 region after the ischemic brain injury in rats.. One hundred male Wistar rats (180-220 g) were divided into ten groups randomly, they were sham operated group (SOG, n = 10), three model group(MG-ld, 3d, 7d, n = 10), as well as three low and high dose astragalan treatment groups (L/H-AGTG-1d, 3d, 7d, n = 10), respectively. And then, middle cerebral artery of MG and AGTG were intercepted by operation inducing brain injured. Their cerebral blood vessel were reperfused on 1, 2, 3 d, respectively, after the L/H-AGTG were treated with the AG (5 mg/kg and 15 mg/kg, ip). After neurologic impairment(NIP) was scored, animals were decapitated to take out hippocampus for counting apoptosis , determining the expression of the NCAM and c-fos by immunohistochemistry method and RT-PCR semiquantitative analysis, respectively.. The NIP scores and apoptotic cell of the L-AGTG and H-AGTG were significantly lower than MG (P < 0.05 or P < 0.01). The expression of NCAM and c-fos were significantly higher than the MG (P < 0.05 or P < 0.01).. Astragalan could improve significantly neural function of ischemia brain injury in rats,the mechanism concerned probably with blocking or reversing apoptosis of hippocampus by promoting the expression of the NCAM and c-fos of hippocampus CA1 region.

Topics: Animals; Apoptosis; Astragalus propinquus; Brain Ischemia; CA1 Region, Hippocampal; Kaempferols; Male; Neural Cell Adhesion Molecules; Neurons; Neuroprotective Agents; Polysaccharides; Rats; Rats, Wistar