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

The effects of anxiolytic honokiol derivative, dihydrohonokiol-B (DHH-B), on amyloid β protein (Aβ25-35, 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 Aβ-induced decrease in neuronal Cl−-ATPase activity without any changes in the activities of Na+/K+-ATPase and anion-insensitive Mg2+-ATPase. A GABAC receptor antagonist (1,2,5,6,-tetrahydropyridin-4-yl) methyl-phosphinic acid (TPMPA, 15 μM), inhibited the protective effects of DHH-B on Cl−-ATPase activity. DHH-B reduced Aβ-induced elevation of [Cl−]i as assayed using a Cl−-sensitive fluorescent dye, and prevented Aβ-induced aggravation of glutamate neurotoxicity. These data suggest that DHH-B exerts the neuroprotective action against Aβ through GABAC receptor stimulation.