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Baicalein Ameliorates Epilepsy Symptoms in a Pilocarpine-Induced Rat Model by Regulation of IGF1R
Neurochemical Research ( IF 3.7 ) Pub Date : 2020-10-23 , DOI: 10.1007/s11064-020-03150-8
Pengfei Fu 1 , Qiang Yuan 1 , Yirui Sun 1 , Xin Wu 1 , Zhuoyin Du 1 , Zhiqi Li 1 , Jin Yu 2 , Ke Lv 1 , Jin Hu 1
Affiliation  

Treatment for epilepsy, particularly temporal lobe epilepsy, is challenging. Baicalein has multiple effects, including anti-inflammatory action. However, little is known about its efficacy in treatment of epilepsy. In this study, we established a pilocarpine-induced rat model and used it for assessment of baicalein efficacy in vivo. We predicted the pharmacological mechanism of baicalein by network pharmacology and RNA sequencing analyses. Pilocarpine epileptic rats treated with baicalein exhibited improved average seizure severity, seizure frequency, seizure duration, and survival time. Network pharmacology and RNA sequencing identified the differentially expressed genes between the baicalein treatment and epileptic groups. Insulin-like growth factor 1 receptor (IGF1R) was chosen as the top candidate target because of its overlapping findings in RNA sequencing and network pharmacology data. Western blotting, immunofluorescence, and polymerase chain reaction analyses showed that baicalein inhibited microglial proliferation, IGF1R, and inflammatory cytokine expression. Moreover, baicalein improved epilepsy symptoms. Inhibition of IGF1R function by blocking with AXL1717 enhanced baicalein treatment efficacy both in vivo and in vitro. In conclusion, baicalein exerted antiepileptic effects by regulation of IGF1R in a pilocarpine-induced rat model.



中文翻译:

黄ical素通过调节IGF1R改善毛果芸香碱诱导的大鼠模型中的癫痫症状。

癫痫,特别是颞叶癫痫的治疗具有挑战性。黄ical素具有多种作用,包括抗炎作用。然而,对其治疗癫痫的功效知之甚少。在这项研究中,我们建立了毛果芸香碱诱导的大鼠模型,并将其用于评估黄ical素的体内功效。我们通过网络药理和RNA测序分析预测了黄ical素的药理机制。用黄ical苷治疗的毛果芸香碱癫痫大鼠表现出改善的平均癫痫发作严重程度,癫痫发作频率,癫痫发作持续时间和存活时间。网络药理学和RNA测序鉴定了黄ical素治疗组和癫痫组之间差异表达的基因。胰岛素样生长因子1受体(IGF1R)被选为最佳候选靶标,因为其在RNA测序和网络药理学数据中的发现相互重叠。Western印迹,免疫荧光和聚合酶链反应分析表明黄ical素抑制小胶质细胞增殖,IGF1R和炎症细胞因子表达。此外,黄ical素改善癫痫症状。通过用AXL1717阻断来抑制IGF1R功能可增强黄ical素在体内和体外的治疗功效。总之,黄ical苷在毛果芸香碱诱导的大鼠模型中通过调节IGF1R发挥抗癫痫作用。此外,黄ical素改善癫痫症状。通过用AXL1717阻断来抑制IGF1R功能可增强黄ical素在体内和体外的治疗功效。总之,黄ical苷在毛果芸香碱诱导的大鼠模型中通过调节IGF1R发挥抗癫痫作用。此外,黄ical素改善癫痫症状。通过用AXL1717阻断来抑制IGF1R功能可增强黄ical素在体内和体外的治疗功效。总之,黄ical苷在毛果芸香碱诱导的大鼠模型中通过调节IGF1R发挥抗癫痫作用。

更新日期:2020-11-25
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