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Anticonvulsive and Neuroprotective Effects of Eupafolin in Rats Are Associated with the Inhibition of Glutamate Overexcitation and Upregulation of the Wnt/β-Catenin Signaling Pathway
ACS Chemical Neuroscience ( IF 4.1 ) Pub Date : 2022-05-02 , DOI: 10.1021/acschemneuro.2c00227
Wei-Horng Jean, Chih-Ta Huang, Jung-Hsuan Hsu, Kuan-Ming Chiu, Ming-Yi Lee, Jiann-Shing Shieh, Tzu-Yu Lin, Su-Jane Wang

Several plant compounds have been found to possess neuroactive properties. The aim of this study was to investigate the anticonvulsant effect of eupafolin, a major active component extracted from Salvia plebeia, a herb used in traditional medicine for its anti-inflammatory properties. To this end, we assessed the anticonvulsant effects of eupafolin in rats intraperitoneally (i.p.) injected with kainic acid (KA) to elucidate this mechanism. Treatment with eupafolin (i.p.) for 30 min before KA administration significantly reduced behavioral and electrographic seizures induced by KA, similar to carbamazepine (i.p.), a widely used antiepileptic drug. Eupafolin treatment also significantly decreased KA seizure-induced neuronal cell death and glutamate elevation in the hippocampus. In addition, eupafolin notably reversed KA seizure-induced alterations in α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor subunit GluR2, glutamate decarboxylase 67 (GAD67, GABAergic enzyme), and Wnt signaling-related proteins, including porcupine, Wnt1, phosphorylated-glycogen synthase kinase-3β, β-catenin, and Bcl-2 in the hippocampus. Furthermore, the increased level of Dickkopf-related protein 1 (Dkk-1, a Wnt signaling antagonist) and the decreased level of Disheveled1 (Dvl-1, a Wnt signaling activator) in the hippocampus of KA-treated rats were reversed by eupafolin. This study provides evidence of the anticonvulsant and neuroprotective properties of eupafolin and of the involvement of regulation of glutamate overexcitation and Wnt signaling in the mechanisms of these properties. These findings support the benefits of eupafolin in treating epilepsy.

中文翻译:

Eupafolin对大鼠的抗惊厥和神经保护作用与抑制谷氨酸过度兴奋和上调Wnt/β-连环蛋白信号通路有关

已发现几种植物化合物具有神经活性特性。本研究的目的是研究从丹参中提取的主要活性成分 eupafolin 的抗惊厥作用,一种用于传统医学的草药,具有抗炎特性。为此,我们评估了红藻氨酸 (KA) 腹膜内 (ip) 注射红藻氨酸 (KA) 大鼠中的桉叶素的抗惊厥作用,以阐明这一机制。在 KA 给药前用 eupafolin (ip) 治疗 30 分钟显着减少了 KA 诱导的行为和电图癫痫发作,类似于广泛使用的抗癫痫药物卡马西平 (ip)。Eupafolin 治疗还显着降低了 KA 癫痫发作引起的海马神经元细胞死亡和谷氨酸升高。此外,eupafolin 显着逆转了 KA 癫痫引起的 α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体亚基 GluR2、谷氨酸脱羧酶 67(GAD67,GABAergic 酶)和 Wnt 信号相关蛋白的改变,包括豪猪,Wnt1,海马中的磷酸化糖原合酶激酶-3β、β-连环蛋白和 Bcl-2。此外,在 KA 处理的大鼠的海马中,Dickkopf 相关蛋白 1(Dkk-1,一种 Wnt 信号传导拮抗剂)水平升高和 Disheveled1(Dvl-1,一种 Wnt 信号激活剂)水平降低被 eupafolin 逆转。这项研究提供了eupafolin 的抗惊厥和神经保护特性以及谷氨酸过度兴奋和Wnt 信号传导参与这些特性机制的调节的证据。这些发现支持eupafolin在治疗癫痫方面的益处。KA 处理的大鼠海马中的 Wnt 信号激活剂)被 eupafolin 逆转。这项研究提供了eupafolin 的抗惊厥和神经保护特性以及谷氨酸过度兴奋和Wnt 信号传导参与这些特性机制的调节的证据。这些发现支持eupafolin在治疗癫痫方面的益处。KA 处理的大鼠海马中的 Wnt 信号激活剂)被 eupafolin 逆转。这项研究提供了eupafolin 的抗惊厥和神经保护特性以及谷氨酸过度兴奋和Wnt 信号传导参与这些特性机制的调节的证据。这些发现支持eupafolin在治疗癫痫方面的益处。
更新日期:2022-05-02
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