Protection against kainate neurotoxicity by ginsenosides: Attenuation of convulsive behavior, mitochondrial dysfunction, and oxidative stress

Abstract

We previously demonstrated that kainic acid (KA)‐mediated mitochondrial oxidative stress contributed to hippocampal degeneration and that ginsenosides attenuated KA‐induced neurotoxicity and neuronal degeneration. Here, we examined whether ginsenosides affected KA‐induced mitochondrial dysfunction and oxidative stress in the rat hippocampus. Treatment with ginsenosides attenuated KA‐induced convulsive behavior dose‐dependently. KA treatment increased lipid peroxidation and protein oxidation and decreased the reduced glutathione/oxidized glutathione (GSH/GSSG) ratio to a greater degree in the mitochondrial fraction than in the hippocampal homogenate. KA treatment resulted in decreased Mn‐superoxide dismutase expression anddiminished the mitochondrial membrane potential. Furthermore, KA treatment increased intramitochondrial Ca²⁺ and promoted ultrastructural degeneration in hippocampal mitochondria. Treatment with ginsenosides dose‐dependently attenuated convulsive behavior and the KA‐induced mitochondrial effects. Protection appeared to be more evident in mitochondria than in tissue homogenates. Collectively, the results suggest that ginsenosides prevent KA‐induced neurotoxicity by attenuating mitochondrial oxidative stress and mitochondrial dysfunction.