Lee Jin-Koo, Choi Seong-Soo, Lee Han-Kyu, Han Ki-Jung, Han Eun-Jung, Suh Hong-Won
Department of Pharmacology and Institute of Natural Medicine, College of Medicine, Hallym University, Chunchon, Kangwon-Do, South Korea.
Planta Med. 2003 Mar;69(3):230-4. doi: 10.1055/s-2003-38475.
In the present study, we examined the effects of ginsenoside Rd (G-Rd) and decursinol (DC) on various neurotoxic responses induced by kainic acid (KA) administered intracerebroventricularly ( i. c. v.) in ICR mice. Ginseng total saponin (GTS) inhibited the KA (0.5 microg)-induced lethal toxicity in a dose-dependent manner. Furthermore, G-Rd, a component of GTS, also attenuated the KA-induced lethal toxicity as well as DC pretreated orally for 30 min. In ICR mouse, neurotoxic damage induced by KA (0.1 microg) in the hippocampus was markedly concentrated in the CA3 pyramidal neurons. G-Rd and DC did not affect the pyramidal cell death in CA3 hippocampal region. In an immunohistochemical study, KA dramatically increased phospho-ERK and decreased phospho-CREB in the hippocampal area. G-Rd and DC attenuated, in part, the increased phospho-ERK and the decreased phospho-CREB protein levels. However, DC potentiated the increased c-Fos and c-Jun protein levels in the hippocampus induced by KA. Thus, our results suggest that the phosphorylation of ERK or the dephosphorylation of CREB protein may play a major role in the regulation of lethal toxicity induced by KA, whereas cell death in the hippocampal CA3 region induced by KA administered i. c. v. may not be directly mediated by ERK phosphorylation and CREB phosphorylation in the mouse.
在本研究中，我们检测了人参皂苷Rd（G-Rd）和紫花前胡醇（DC）对在ICR小鼠脑室内注射（i.c.v.）海藻酸（KA）诱导的各种神经毒性反应的影响。人参总皂苷（GTS）以剂量依赖的方式抑制KA（0.5微克）诱导的致死毒性。此外，GTS的成分G-Rd以及口服预处理30分钟的DC也减轻了KA诱导的致死毒性。在ICR小鼠中，KA（0.1微克）在海马体中诱导的神经毒性损伤明显集中在CA3锥体神经元。G-Rd和DC不影响海马体CA3区的锥体细胞死亡。在一项免疫组织化学研究中，KA显著增加了海马区的磷酸化细胞外信号调节激酶（phospho-ERK）并降低了磷酸化cAMP反应元件结合蛋白（phospho-CREB）。G-Rd和DC部分减轻了磷酸化ERK增加和磷酸化CREB蛋白水平降低的情况。然而，DC增强了KA诱导的海马体中c-Fos和c-Jun蛋白水平的增加。因此，我们的结果表明，ERK的磷酸化或CREB蛋白的去磷酸化可能在调节KA诱导的致死毒性中起主要作用，而脑室内注射KA诱导的小鼠海马体CA3区细胞死亡可能不是直接由ERK磷酸化和CREB磷酸化介导的。
