Ginsenoside Re blocks Bay k-8644-induced neurotoxicity via attenuating mitochondrial dysfunction and PKCδ activation in the hippocampus of mice: Involvement of antioxidant potential.

Although the anticonvulsant effects of ginsenosides are recognized, little is known about their effects on the convulsive behaviors induced by the activation of L-type Ca ²⁺ channels. Here, we investigated whether ginsenoside Re (GRe) modulates excitotoxicity induced by the L-type Ca ²⁺ channel activator Bay k-8644. GRe significantly attenuated Bay k-8644-induced convulsive behaviors and hippocampal oxidative stress in mice. GRe-mediated antioxidant potential was more pronounced in the mitochondrial fraction than cytosolic fraction. As L-type Ca ²⁺ channels are thought to be targets of protein kinase C (PKC), we investigated the role of PKC under excitotoxic conditions. GRe attenuated Bay k-8644-induced mitochondrial dysfunction, PKCδ activation, and neuronal loss. The PKCδ inhibition and neuroprotection mediated by GRe were comparable to those by the ROS inhibitor N-acetylcysteine, the mitochondrial protectant cyclosporin A, the microglial inhibitor minocycline, or the PKCδ inhibitor rottlerin. Consistently, the GRe-mediated PKCδ inhibition and neuroprotection were counteracted by the mitochondrial toxin 3-nitropropionic acid or the PKC activator bryostatin-1. GRe treatment did not have additional effects on PKCδ gene knockout-mediated neuroprotection, suggesting that PKCδ is a molecular target of GRe. Collectively, our results suggest that GRe-mediated anticonvulsive/neuroprotective effects require the attenuation of mitochondrial dysfunction and altered redox status and inactivation of PKCδ.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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