谷氨酸诱导的神经毒性是神经系统疾病中最重要的致病机制之一,被广泛用作缺血性中风的体外模型。SenkyunolideI(SEI),一种来源于中药川芎的有效成分。和当归(Oliv。)Diels,已被证明对大鼠局灶性脑缺血再灌注具有有益作用。然而,SEI介导的神经保护的潜在机制尚不清楚.因此,我们探讨了SEI在谷氨酸介导的小鼠神经母细胞瘤(Neuro2a)细胞损伤中的影响,并确定了相关机制。Neuro2a细胞在暴露于谷氨酸的条件下用SEI处理24小时。通过使用WST-1试剂评估细胞活力,使用膜联蛋白V-FITC和PI双染色试剂盒评估细胞凋亡。p-AKT的蛋白表达水平,AKT,p-GSK3β,GSK3β,p-p38,p38,p-ERK,ERK,p-JNK,JNK,Bcl-2,Bax,Bcl-xl,p-Bad,糟糕,通过蛋白质印迹分析确定p53和裂解的胱天蛋白酶-3。谷氨酸能显著降低细胞活力,提高细胞凋亡水平。用SEI治疗逆转了这些效应。此外,用SEI处理后,p-JNK/JNK和裂解的caspase-3的表达也降低。我们的发现表明,SEI通过调节JNK/caspase-3通路和凋亡保护Neuro2a细胞免受谷氨酸毒性。因此,SEI可能是神经保护的有希望的候选人。
Glutamate-induced neurotoxicity is one of the most important pathogenic mechanisms in neurological diseases and is widely used as an in vitro model for ischemic stroke. Senkyunolide I (SEI), an active constituent derived from traditional Chinese medicine Ligusticum chuanxiong Hort. and Angelica sinensis (Oliv.) Diels, has been shown to have beneficial effects against focal cerebral ischemia-reperfusion in rats. However, the mechanisms underlying SEI-mediated neuroprotection remain not well understood. Thus, we explored the influence of SEI in glutamate-mediated injury to mouse neuroblastoma (Neuro2a) cells and determined the mechanisms involved. Neuro2a cells were treated with SEI under exposure to glutamate for 24 h. Cell viability was assessed by using WST-1 reagents, and apoptosis was evaluated using Annexin V-FITC and a PI double staining kit. The protein expression levels of p-AKT, AKT, p-GSK3β, GSK3β, p-p38, p38, p-ERK, ERK, p-JNK, JNK, Bcl-2, Bax, Bcl-xl, p-Bad, Bad, p53, and cleaved caspase-3 were determined by Western blot analysis. Glutamate significantly decreased cell viability and elevated the level of apoptosis. Treatment with SEI reversed those effects. Furthermore, the expression of p-JNK/JNK and cleaved caspase-3 were also reduced after treatment with SEI. Our findings demonstrate that SEI protected Neuro2a cells against glutamate toxicity by regulating JNK/caspase-3 pathway and apoptosis. Thus, SEI maybe a promising candidate for neuroprotection.