Dehydroeffusol Pprevents Amyloid β-mediated Hippocampal Neurodegeneration via Reducing Intracellular Zn Toxicity.

Dehydroeffusol, a phenanthrene isolated from Juncus effusus, is a Chinese medicine. To explore an efficacy of dehydroeffusol administration for prevention and cure of Alzheimer's disease, here we examined the effect of dehydroeffusol on amyloid β (Aβ)-mediated hippocampal neurodegeneration. Dehydroeffusol (15 mg/kg body weight) was orally administered to mice once a day for 6 days and then human Aβ was injected intracerebroventricularly followed by oral administration for 12 days. Neurodegeneration in the dentate granule cell layer, which was determined 2 weeks after Aβ injection, was rescued by dehydroeffusol administration. Aβ staining (uptake) was not reduced in the dentate granule cell layer by pre-administration of dehydroeffusol for 6 days, while increase in intracellular Zn induced with Aβ was reduced, suggesting that pre-administration of dehydroeffusol prior to Aβ injection is effective for Aβ-mediated neurodegeneration that was linked with intracellular Zn toxicity. As a matter of fact, pre-administration of dehydroeffusol rescued Aβ-mediated neurodegeneration. Interestingly, pre-administration of dehydroeffusol increased synthesis of metallothioneins, intracellular Zn-binding proteins, in the dentate granule cell layer, which can capture Zn from Zn-Aβ complexes. The present study indicates that pre-administration of dehydroeffusol protects Aβ-mediated neurodegeneration in the hippocampus by reducing intracellular Zn toxicity, which is linked with induced synthesis of metallothioneins. Dehydroeffusol, a novel inducer of metallothioneins, may protect Aβ-induced pathogenesis in Alzheimer's disease.