Anemonin Alleviates Nerve Injury After Cerebral Ischemia and Reperfusion (I/R) in Rats by Improving Antioxidant Activities and Inhibiting Apoptosis Pathway

In the present study, we aimed at evaluating the potential neuroprotective effect and the underlying mechanism of anemonin against cerebral ischemia and reperfusion (I/R) injury. Anemonin was administered to rats by the intraperitoneally (i.p.) route once daily for 7 days before middle cerebral artery occlusion (MCAO). Focal cerebral ischemia was induced by 90 min of MCAO followed by 24 h of reperfusion. After that, animals were sacrificed by decapitation, brain was removed, and various biochemical estimations, neurological status, and assessment of cerebral infarct size were carried out. MCAO followed by 24 h of reperfusion caused a significant increase in infarct size, neurological deficit score, malondialdehyde (MDA) content, reactive oxygen species (ROS) level, and DNA fragmentation, as well as a decrease in the activities of superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), glutathione peroxidase (GPx), and Na+, K+-ATPase in the brain. Furthermore, elevated Bax expression, increased caspase-3 cleavage, and decreased Bcl-2 expression were observed in nontreated rats in response to focal cerebral I/R injury. However, pretreatment with anemonin significantly reversed these levels of biochemical parameters, reduced cerebral infarct size, and improved the neurologic score in cerebral ischemic animals. Additionally, a wide distribution of anemonin in plasma and brain tissues and the brain-to-plasma partition coefficient (Ri) ratio of 0.7 at 90 min indicated that this compound could penetrate the blood-brain barrier (BBB). These results showed that pretreatment with anemonin provided a significant protection against cerebral I/R injury in rats by, at least in part, its antioxidant action and consequent inhibition of apoptosis.