Chemically Bonding of Amantadine with Gardenamide A Enhances the Neuroprotective Effects against Corticosterone-Induced Insults in PC12 Cells

Int J Mol Sci. 2015 Sep 21;16(9):22795-810. doi: 10.3390/ijms160922795.

Abstract

Two amantadine (ATD)-gardenamide A (GA) ligands have been designed and synthesized. The bonding of ATD with GA through a methylene carbonyl brigde (L1) enhances the neuroprotective effect against corticosterone (CORT)-induced impairments in PC12 cells; while the bonding through a succinyl brigde (L2) does not. L1 reduces the level of reactive oxygen species (ROS) and cell apoptosis generated by CORT. It restores CORT-changed cell morphology to a state that is closed to normal PC12 cells. One mechanism of L1 to attenuate CORT-induced cell apoptosis is through the adjustment of both caspase-3 and Bcl-2 proteins. Like GA, both nNOS and eNOS might be involved in the neuroprotective mechanism of L1. All the evidences suggest that L1 may be a potential agent to treat depression.

Keywords: NMDA; amantadine; eNOS; gardenamide A; nNOS; neuroprotection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amantadine / analogs & derivatives*
  • Amantadine / pharmacology*
  • Animals
  • Apoptosis / drug effects*
  • Corticosterone / adverse effects
  • Iridoids / chemistry*
  • Iridoids / pharmacology*
  • Neuroprotective Agents / chemistry*
  • Neuroprotective Agents / pharmacology*
  • PC12 Cells
  • Rats
  • Reactive Oxygen Species / metabolism

Substances

  • Iridoids
  • Neuroprotective Agents
  • Reactive Oxygen Species
  • gardenamide A
  • Amantadine
  • Corticosterone