Abstract
Inflammation and oxidative stress play an important part in the pathogenesis of focal cerebral ischemia/reperfusion (I/R) injury, resulting in neuronal death. The signaling pathways involved and the underlying mechanisms of these events are not fully understood. Chrysin, which is a naturally occurring flavonoid, exhibits various biological activities. In this study, we investigated the neuroprotective properties of chrysin in a mouse model of middle cerebral artery occlusion (MCAO). To this end, male C57/BL6 mice were pretreated with chrysin once a day for seven days and were then subjected to 1 h of middle cerebral artery occlusion followed by reperfusion for 24 h. Our data show that chrysin successfully decreased neurological deficit scores and infarct volumes, compared with the vehicle group. The increases in glial cell numbers and proinflammatory cytokine secretion usually caused by ischemia/reperfusion were significantly ameliorated by chrysin pretreatment. Moreover, chrysin also inhibited the MCAO-induced up-regulation of nuclear factor-kappa B (NF-κB), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS), compared with the vehicle. These results suggest that chrysin could be a potential prophylactic agent for cerebral ischemia/reperfusion (I/R) injury mediated by its anti-inflammatory and anti-oxidative effects.
Highlights
Stroke is believed to be the second most common cause of death and the main factor leading to long-term disability as a result in irreversible brain injury and loss of neuronal function [1]
Multiple previous studies conducted in various animal models, have shown that chrysin exerts anti-inflammatory and neuroprotective effects when administered at doses ranging from 25 to 100 mg/kg/day [6,16,17]
In this study, we first evaluated the clinical scores in a mouse model of middle cerebral artery occlusion (MCAO) following pretreatment with chrysin at the 25, 50, 75, and 100 mg/kg
Summary
Stroke is believed to be the second most common cause of death and the main factor leading to long-term disability as a result in irreversible brain injury and loss of neuronal function [1]. Several neuroprotective agents have been investigated in preclinical studies, none have demonstrated efficacy in clinical practice. The benefits of traditional Chinese medicines exhibiting neuroprotective effects have been increasingly investigated in I/R injury [3]. Chrysin has the ability to block the cell cycle, induce apoptosis [10], disrupt mitotic spindle formation [11] and inhibit angiogenesis [12], making it a potential candidate as an anticancer drug. Studies have shown that chrysin inhibits the NF-κB signaling pathway, providing an underlying mechanism for its anti-inflammatory activity [13,14,15]
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