Ameliorating effects of Kangen-karyu on neuronal damage in rats subjected to repeated cerebral ischemia

Fengling Pu, Tomohiro Kaneko, Makiko Enoki, Keiichi Irie, Takuya Okamoto, Yasuo Sei, Nobuaki Egashira, Ryozo Oishi, Kenichi Mishima, Hidetoshi Kamimura, Katsunori Iwasaki, Michihiro Fujiwara

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Abstract

We previously reported that 21-day (14-day pre-ischemic and 7-day post-ischemic) treatment with Kangen-karyu (KGKR) improved spatial memory impairment and hippocampal neuronal death induced by repeated cerebral ischemia (2 × 10-min, 1-h interval) in rats. In the present study, we examined the effect of single and 14-day pre-ischemic KGKR treatment on neuronal damage in the same repeated cerebral ischemia model. Additionally, to determine the mechanisms of neuroprotection by KGKR at glutamatergic neurons, we examined the effects of KGKR on glutamate release induced by repeated cerebral ischemia in vivo, and on cell damage induced by both glutamate and kainate in primary cultured hippocampal neurons in vitro. The 14-day pre-ischemic KGKR (300 mg/kg, oral administration (p.o.)) treatment reduced neuronal damage and astrocyte expression induced by repeated cerebral ischemia. No effect was observed after single pre-ischemic KGKR treatment. Both single and 14-day KGKR treatment decreased glutamate release in the hippocampal CA1 region in intact rats; however, neither pre-ischemic KGKR treatment altered glutamate release during cerebral ischemia. In vitro, KGKR (100-1000 μg/mL) dose-dependently suppressed hippocampal neuronal damage induced by both glutamate (100 μM) and kainate (1 mM). These data suggest neuroprotection with KGKR requires continuous preischemic treatment, and that the mechanisms of protection may be involved in inhibiting the glutamatergic receptors of the post-synaptic neurons.

Original languageEnglish
Pages (from-to)167-174
Number of pages8
JournalJournal of Natural Medicines
Volume64
Issue number2
DOIs
Publication statusPublished - Apr 1 2010

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science
  • Drug Discovery
  • Complementary and alternative medicine
  • Organic Chemistry

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    Pu, F., Kaneko, T., Enoki, M., Irie, K., Okamoto, T., Sei, Y., Egashira, N., Oishi, R., Mishima, K., Kamimura, H., Iwasaki, K., & Fujiwara, M. (2010). Ameliorating effects of Kangen-karyu on neuronal damage in rats subjected to repeated cerebral ischemia. Journal of Natural Medicines, 64(2), 167-174. https://doi.org/10.1007/s11418-010-0392-y