It is reported that baicalein can activate PI3K/AKT pathway, inhibit caspase activation and reduce cerebral infarct volume in middle cerebral artery occlusion (MCAO) rats. However, a caspase-independent mechanism initiated by poly (ADP-ribose) polymerase-1 (PARP-1) activation has been reported to make more contribution to cells death after ischemic stroke. In the present study, we established a cerebral ischemia/reperfusion (I/R) rat model through middle cerebral artery occlusion following reperfusion to investigate the mechanisms of ischemic tissue recovery following baicalein treatment. The data showed that baicalein treatment at dose of 100 mg/kg for 7 days significantly inhibited the release of cytokines, activation of PARP-1, nuclear translocation of apoptosis-inducing factor (AIF) and macrophage migration inhibitory factor (MIF) in cerebral I/R rats, therefore decreased cerebral infarct volume and neurological scores. Then, we further investigated the signal transduction mechanisms of ischemic tissue protection by baicalein in vitro. Following oxygen and glucose deprivation (OGD) in SH-SY5Y cells, the mitochondrial AIF was translocated into nucleus after 12 h. The co-immunoprecipitation analysis showed that the interaction between AIF and MIF was activated by OGD and subsequently resulted in MIF nuclear translocation. Also, the baicalein inhibited apoptosis, reduced oxidative stress, protected mitochondrial function and restored mitochondrial membrane potential in OGD cells. The results obtained from both in vivo and in vitro study demonstrated the PARP-1/AIF pathway involved in mechanisms of baicalein to protect the cerebral tissues from ischemic injury.

中文翻译：

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黄ical素通过抑制脑缺血/再灌注大鼠中的PARP-1活化和AIF核易位，减轻caspase依赖性细胞的死亡。

据报道，黄ical素可以激活PI3K / AKT通路，抑制半胱天冬酶的活化并减少大脑中动脉阻塞（MCAO）大鼠的脑梗死体积。但是，据报道由聚（ADP-核糖）聚合酶-1（PARP-1）激活引发的半胱天冬酶非依赖性机制对缺血性中风后细胞死亡做出了更多贡献。在本研究中，我们通过再灌注后大脑中动脉闭塞建立了脑缺血/再灌注（I / R）大鼠模型，以研究黄ical素治疗后缺血组织恢复的机制。数据显示，以100 mg / kg剂量的黄ical素治疗7天可显着抑制细胞因子的释放，PARP-1的激活，I / R大鼠脑中凋亡诱导因子（AIF）和巨噬细胞迁移抑制因子（MIF）的核易位，因此降低了脑梗死的体积和神经学评分。然后，我们进一步研究了黄ical苷在体外对缺血组织保护的信号转导机制。在SH-SY5Y细胞中缺氧和缺糖（OGD）之后，线粒体AIF在12小时后转移到核中。免疫共沉淀分析表明，OGD激活了AIF和MIF之间的相互作用，并随后导致MIF核易位。此外，黄ical素抑制OGD细胞的凋亡，降低氧化应激，保护线粒体功能并恢复线粒体膜电位。