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Drug Development

開催日 2014/9/13
時間 11:00 - 12:00
会場 Poster / Exhibition(Event Hall B)

Effects of Dihydrohonokiol-B on amyloidβ1-42-induced neuronal cell death in rat cultured hippocampal cells

  • P3-049
  • 中山 靖久 / Yasuhisa Nakayama:1 中邨 智之 / Tomoyuki Nakamura:1 
  • 1:関西医科大学 / Dept Pharm, Kansai Med Univ, Osaka, Japan 

Honokiol is isolated and purified from the bark of Magnolia officinalis Rehd. et Wils, which have been used in traditional Chinese medicine. Dihidrohonokiol-B (DHH-B) is a partially reduced derivative of honokiol. DHH-B reportedly showed a potent anxiolytic effect and impaired learning and memory performance. We previously reported that DHH-B protected pathophysiological concentration of amyloidβ25-35 (Aβ25-35)/glutamate-induced cell death. However, protective effects against Aβ1-42, regarding as the main pathogenic species causing Alzheimer's disease, and intracellular mechanisms of DHH-B are little known. In this study, we attempted to elucidate the neuroprotective effects of DHH-B, especially focusing on the extracellular signal-regulated kinases (ERK1/2) signaling pathway and axonal growth in rat cultured hippocampal neurons. Cultured rat hippocampal neuronal cells exposed to Aβ1-42 increased the number of apoptotic cells and caspase-3 activation. and suppressed ERK1/2 phosphorylation. Pretreatment of hippocampal neuronal cells with DHH-B suppressed increases of cleaved caspase-3 induced by Aβ1-42 in a dose-dependent manner. DHH-B also recovered suppression of ERK1/2 phosphorylation by Aβ1-42. Pretreatment with MAPK kinase inhibitor, U0126, inhibited recovery effects by DHH-B such as phosphorylation of ERK1/2.
Treatment with DHH-B significantly increased multiple features of nerve cell morphology, including neurite length and number of outgrowth. Pretreatment with U0126 inhibited neurotrophic effects by DHH-B. Bisindolylmaleimide I, protein kinase C inhibitor, or H-89, protein kinase A inhibitor, partially inhibited neurotrophic effects by DHH-B. Neurite outgrowth was suppressed by adding Aβ1-42 to normal culture medium. These suppressive effects by Aβ1-42 was recovered by DHH-B.
These results suggested that DHH-B exerts a protective effects against apoptosis induced by Aβ1-42 through recovery of protein kinase C-ERK1/2 pathway and activation of neurite outgrowth.

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