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.
Highlights
It has been estimated that millions of people suffer from ischemic stroke annually [1]
The number of live cells in the hippocampus is sharply increased by puerarin pretreatment.We further observed that the levels of phosphorylated Akt1, glycogen synthase kinase 3β (GSK-3β) and MCL-1were elevated and those of cleaved-caspase-3 were reduced in the puerarin-treatment group
Our findings suggest that puerarin protects the hippocampus from I/R damage by activating the phosphatidylinositol 3-kinase (PI3K)/Akt1/GSK-3β/myeloid cell leukemia-1 (MCL-1) signaling pathway
Summary
It has been estimated that millions of people suffer from ischemic stroke annually [1]. Ischemic stroke, caused by the rupture or occlusion of blood vessels, can compromise cell function and disrupt the equilibrium of brain structures, leading to complex brain disorders [2, 3]. Its pharmacological activities have been extensively investigated [6]. Various diseases, such as cardiovascular dysfunction, neurological disorder and liver injury, may be treated using puerarin [6]. It has been suggested that puerarin significantly reduces infarct size in transient middle cerebral artery occlusion (MCAO) models [9]. It is still unknown whether puerarin protects the hippocampus from global ischemia/reperfusion (I/R) damage
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