Effusol, a unique Juncus effusus phenanthrene, ameliorates amyloid β1-42-mediated neurotoxicity in mice

Dehydroeffusol, a unique Juncus effusus phenanthrene, ameliorates amyloid β _1-42 (Aβ _1-42 )-mediated neurotoxicity. We tested the ameliorating effect of effusol, another unique Juncus effusus phenanthrene. Effusol (15 mg/kg) was orally delivered to mice once a day for 2 days and mice were subjected to intracerebroventricular (ICV) administration of Aβ _1-42 1 day after the last deliver of effusol in the same procedure as dehydroeffusol. Fourteen days later, effusol ameliorated neurotoxicity in the dentate granule cell layer evaluated by propidium iodide. Effusol did not increase the synthesis of metallothioneins (MTs) for capturing toxic Zn ²⁺ ferried by Aβ _1-42 , unlike the effect of dehydroeffusol via MT synthesis. However, effusol reduced both intracellular increases in Zn ²⁺ and reactive oxygen species (ROS) by Aβ _1-42 . To test the effect of post-intake of effusol, mice were subjected to ICV administration of Aβ _1-42 and effusol was delivered to mice in the same manner. Effusol ameliorated Aβ _1-42 -mediated neurotoxicity. These results first suggest that effusol ameliorates Aβ _1-42 -mediated neurotoxicity in the dentate gyrus by reducing intracellular ROS generation, which is induced by Zn ²⁺ dysregulation. A possible effect of effusol on Aβ _1-42 neurotoxicity is that effusol may reduce Aβ-induced synaptic hyperexcitation induced by glutamate exocytosis via activating GABA _A receptors followed by ameliorating Zn ²⁺ dysregulation.