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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.

To characterize the antinociceptive profiles of Angelica gigas NAKAI (ANG; Korean angelica), methanol extract from the dried roots of ANG was made and mice were administered orally at the various doses (from 0.25 to 3 g/kg). ANG produced the increased latencies of the tail-flick and hot-plate paw-licking responses in a dose-dependent manner. In acetic acid-induced writhing test, ANG dose-dependently decreased writhing numbers. Moreover, the cumulative response time of nociceptive behaviors induced by intraplantar formalin injection was reduced during both the 1st and the 2nd phases in a dose-dependent manner in ANG-treated mice. Furthermore, oral administration of ANG did not cause licking, scratching and biting responses induced by TNF-alpha (100 pg), IFN-gamma (100 pg) or IL-1beta (100 pg) injected intrathecally (i.t.), especially at higher dose (3 g/kg). Additionally, in ANG treated mice, the cumulative nociceptive response time for i.t. administration of substance P or capsaicin was dose-dependently diminished. Finally, nociceptive responses elicited by i.t. injection of glutamate (20 microg), N-methyl-D-aspartic acid (60 ng), alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (13 ng) or kainic acid (12 ng) were decreased by oral administration of ANG. Our results suggest that ANG produces antinociception via acting on the central nervous system and shows antinociceptive profiles in various pain models, especially inflammatory pain.

Platycodin D (PD), one of several triterpene saponins, was isolated from roots of Platycodon grandiflorum. We previously reported that intracerebroventricular (i.c.v.) administration of PD showed an antinociceptive effect as measured by the tail-flick assay. However, its exact role in the regulation of antinociception in the various types of pain models has not yet been characterized. Thus, we attempted to find antinociceptive profiles of PD in various pain models. PD administered intraperitoneally (i.p.), i.c.v. or intrathecally (i.t.) showed antinociceptive effects in dose-dependent manners as measured by the tail-flick, writhing and formalin tests. In the tail-flick test, PD at the low doses reached the peak after 15 minutes and returned to the control level after 60 minutes. However, higher doses of PD showed a strong antinociception at least for 1 hour. PD administered i.t. showed stronger antinociception than that induced by i.c.v. administration PD in both tail-flick and writhing tests. In the formalin test, PD administered i.p., i.c.v. or i.t. showed antinociceptive effects during both the first (direct nociceptive stimulation) and second (late inflammatory) phases. Pretreatment with naltrexone i.p., i.c.v. or i.t. did not affect PD-induced inhibition of the tail-flick response. Our results suggest that PD shows a strong antinociceptive effect on the tail-flick, writhing and formalin tests, acting on central nervous system. However, PD-induced antinociception may not be mediated by the opioid receptors.

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