Puerarin attenuates locomotor and cognitive deficits as well as hippocampal neuronal injury through the PI3K/Akt1/GSK-3β signaling pathway in an in vivo model of cerebral ischemia

Abstract

Ischemic stroke causes irreversible damage to the brain. The hippocampus is a vulnerable region and plays an important role in cognition and locomotor activity. Puerarin is a phytoestrogen that has beneficial effects in treating neurological disorders. How puerarin protects against hippocampal injury and its molecular mechanisms remain to be elucidated. Transient global brain ischemia was induced by 4-vessel occlusion in adult male Sprague-Dawley rats. The rats were pretreated with puerarin alone or together with LY294002 (an PI3K inhibitor) before ischemia/reperfusion (I/R). The open- and closed-field tasks and Morris water maze (MWM) test were used to assess the effects of puerarin on anxiety-like behavioral and cognitive impairment following I/R. Hematoxylin-eosin staining(HE) was used to examine the survival of hippocampal CA1 pyramidal neurons, and immunoblotting was performed to examine the expression of the related proteins. By using the rat model for transient I/R, we demonstrated that puerarin pretreatment significantly increased the travelling distance and number of crossings in the open- and closed-field tests, reduced latency and increased the proportion of distance and time in zone IV in the MWM. The number of live cells in the hippocampus is sharply increased by puerarin pretreatment.We further observed that the levels of phosphorylated Akt1, GSK-3β and MCL-1were elevated and those of cleaved-caspase-3 were reduced in the puerarin-treatment group. Notably, the PI3K inhibitor LY294002 counteracted all of the effects of puerarin. Our findings suggest that puerarin protects the hippocampus from I/R damage by activating the PI3K/Akt1/GSK-3β/MCL-1 signaling pathway.

Phytoestrogen coumestrol attenuates brain mitochondrial dysfunction and long‐term cognitive deficits following neonatal hypoxia–ischemia

“…Once the events that led to hippocampal damage had already initiated, we speculate that a higher dose of coumestrol would be necessary. In previous reports on experimental global cerebral ischemia, a single dose of coumestrol or other phytoestrogens were administered pre‐ or post‐insult, was able to protect the vulnerable hippocampal CA1 and to prevent cell death, thus significantly reducing the lesion volume (Canal Castro et al, 2012; Tao et al, 2017; Wang et al, 2013). Based in our data, it can be suggested that the beneficial effects of coumestrol are determined by mitigating the late tissue loss and late astrocytic activation in ipsilesional hippocampus after HI insult.…”

Puerarin Relieved Compression-Induced Apoptosis and Mitochondrial Dysfunction in Human Nucleus Pulposus Mesenchymal Stem Cells via the PI3K/Akt Pathway

“…Moreover, the ERK1/2-Runx2 signaling pathway was engaged in the mechanism of PUR in promoting osteogenic differentiation [28]. PUR could attenuate hippocampal neuronal injury through the PI3K/Akt1/GSK-3β signaling pathway [29]. In our previous studies, the PI3K/Akt signaling pathway was found to be significantly activated in the protective effect of icariin on human NPCs [30] in unfavorable inflammatory microenvironment.…”

“…Stem Cells International antiapoptosis agent, which can also activate the PI3K/Akt pathway [51]. Specifically, PUR could attenuate cognitive deficits by increasing survival hippocampal CA1 pyramidal neurons [29] and remit daunorubicin-induced apoptosis of H9c2 cells [51] through Akt phosphorylation. Similarly, based on our findings, the PI3K/Akt pathway was inhibited in human NPMSCs under compression, and PUR treatment could reactivate the pathway.…”

Protective effect of extract of the Camellia japonica L. on cerebral ischemia-reperfusion injury in rats

“…The Morris maze test is a well-proven method for evaluating place navigation and spatial ability to assess spatial reference memory in rodents. The procedure is divided into two phases: place navigation and spatial probe 20 . In the place navigation trial, rats were trained to find the escape platform.…”