Effects of ginsenoside Rd and decursinol on the neurotoxic responses induced by kainic acid in mice.
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.
Lee
Jin-Koo
JK
Department of Pharmacology and Institute of Natural Medicine, College of Medicine, Hallym University, Chunchon, Kangwon-Do, South Korea.
Choi
Seong-Soo
SS
Lee
Han-Kyu
HK
Han
Ki-Jung
KJ
Han
Eun-Jung
EJ
Suh
Hong-Won
HW
D029969:Angelica; D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology*; D002087:Butyrates / Q000494:pharmacology*; D036145:Ginsenosides / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects*; D007150:Immunohistochemistry; D007608:Kainic Acid; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D018696:Neuroprotective Agents / Q000494:pharmacology*; D005894:Panax; D008517:Phytotherapy; D028321:Plant Preparations / Q000494:pharmacology
D001578:Benzopyrans; D002087:Butyrates; D036145:Ginsenosides; D018696:Neuroprotective Agents; D028321:Plant Preparations; C101278:decursin; D007608:Kainic Acid; C049863:ginsenoside Rd