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Drug Development and Neuroprotection

開催日 2014/9/11
時間 9:00 - 10:00
会場 Room J(313+314)
Chairperson(s) 池田 華子 / Hanako Ohashi-Ikeda (京都大学医学部附属病院 臨床研究総合センター / Institute for Advancement of Clinical and Translational Science, Kyoto University Hospital, Japan)
東田 千尋 / Chihiro Tohda (富山大学和漢医薬学総合研究所神経機能学分野 / Division of Neuromedical Science, Institute of Natural Medicine, University of Toyama, Japan)

The recovery of motor function by a crude drug and its active constituent in spinal cord injured mice

  • O1-J-1-1
  • 田辺 紀生 / Norio Tanabe:1 久保山 友晴 / Tomoharu Kuboyama:1 数馬 恒平 / Kohei Kazuma:2 紺野 勝弘 / Katsuhiro Konno:2 東田 千尋 / Chihiro Tohda:1 
  • 1:富山大・和漢研・神経機能学 / Div. of Neuromedical Science, Inst. of Natural Medicine, Univ. of Toyama, Toyama, Japan 2:富山大・和漢研・和漢薬製剤開発 / Div. of Kampo-Pharmaceutics, Inst. of Natural Medicine, Univ. of Toyama, Toyama, Japan 

After spinal cord injury (SCI), astrocytes are increased and secrete chondroitin sulfate proteoglycan (CSPG) in the injured region. Since the CSPG inhibits axonal extension, broken neuronal tracts are hardly reconstructed, and motor function is not restored. Therefore, axonal extension in the inhibitory environment is one of essential factors for recovery from motor dysfunction. In this study, we aimed to identify drugs that were able to induce axonal extension on the inhibitory CPSG substrate and improve motor function in SCI mice.
Water extracts of crude drugs used in traditional Japanese medicine (110 kinds) were screened for axonal extension activity on the inhibitory CPSG substrate. The water extracts of crude drugs or vehicle solution was treated to cultured cortical neurons (ddY mice, E14) on the CSPG. Four days after that, axonal lengths were evaluated by immunocytochemistry for pNF-H. Although axonal extension was inhibited on the CSPG, the water extract of crude drug X (X extract, 10 μg/ml) strongly induced axonal extension in the presence of the inhibitory CSPG. Next, an effect of X extract was investigated using SCI mice (ddY, female, 8 weeks old) suffered from contusion injury. Consecutive oral administrations of X extract (500 mg/kg/day) or vehicle solution to SCI mice was started from 1h after the injury. Administration of X extract for 31 days significantly recovered motor function of hindlimbs in SCI mice and increased axonal density of 5-HT-positive raphe spinal tracts in the injured region. Because compound A was identified as an active constituent in X extract in vitro experiments, compound A (100 μmol/kg/day, for 31 days) was orally administrated to SCI mice. As a result, compound A significantly recovered the motor function of hindlimbs in SCI mice.
In this study, we demonstrated beneficial effects of the extract of crude drug X on SCI mice, and identified the active constituent in the extract. These drugs are new candidates for SCI treatment.

*Crude drug X and compound A are not open due to patent matters.

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