Effects of Ginsenoside Rd and Decursinol on the Neurotoxic Responses Induced by Kainic Acid in Mice

Abstract

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 μg)-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 μg) 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.

Abbreviations

KA:Kainic acid

G-Rd:Ginsenoside Rd

DC:Decursinol

i. c. v.:intracerebroventricular

CNS:Central nervous system

DG:dentate gyrus

MAPK:Mitogen-activated protein kinase

ERK:Extracellular signal-regulated protein kinase

CREB:cyclic AMP-response element binding protein

IR:Immunoreactivity

S.E.M.:Standard error of the means

Key words

Ginsenoside Rd - Panax ginseng C. A. Meyer - Araliaceae - decursinol - Angelica gigas Nakai - Umbelliferae - hippocampal cell death - kainic acid - lethality - ERK - CREB

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