Anxiolytic agent, dihydrohonokiol-B, recovers amyloid beta protein-induced neurotoxicity in cultured rat hippocampal neurons

  • Neurosci Lett. 2005 Aug;384(1-2):44-7. doi: 10.1016/j.neulet.2005.04.081.
Bing Liu  1 ,  Naoki Hattori ,  Nan-Yan Zhang ,  Bo Wu ,  Li Yang ,  Kaori Kitagawa ,  Zheng-Mei Xiong ,  Takao Irie ,  Chiyoko Inagaki
Affiliations
  • 1. Department of Pharmacology, Kansai Medical University, 10-15 Fumizono-cho, Moriguchi City, Osaka 570-8506, Japan.
PMID: 15899548 DOI: 10.1016/j.neulet.2005.04.081
Abstract

The effects of anxiolytic honokiol derivative, dihydrohonokiol-B (DHH-B), on amyloid beta protein (Abeta(25-35), 10 nM)-induced changes in Cl(-)-ATPase activity, intracellular Cl- concentration ([Cl-]i) and glutamate neurotoxicity were examined in cultured rat hippocampal neurons. DHH-B (10 ng/ml) recovered Abeta-induced decrease in neuronal Cl(-)-ATPase activity without any changes in the activities of Na+/K+-ATPase and anion-insensitive Mg2+-ATPase. A GABA(C) receptor antagonist (1,2,5,6,-tetrahydropyridin-4-yl) methyl-phosphinic acid (TPMPA, 15 microM), inhibited the protective effects of DHH-B on Cl(-)-ATPase activity. DHH-B reduced Abeta-induced elevation of [Cl-]i as assayed using a Cl(-)-sensitive Fluorescent Dye, and prevented Abeta-induced aggravation of glutamate neurotoxicity. These data suggest that DHH-B exerts the neuroprotective action against Abeta through GABA(C) receptor stimulation.

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