Ginsenoside Re blocks Bay k-8644-induced neurotoxicity via attenuating mitochondrial dysfunction and PKCδ activation in the hippocampus of mice: Involvement of antioxidant potential
- Authors
- Tran, Ngoc Kim Cuong; Jeong, Ji Hoon; Sharma, Naveen; Nguyen, Yen Nhi Doan; Tran, Hoang-Yen Phi; Dang, Duy-Khanh; Park, Jung Hoon; Byun, Jae Kyung; Jin, Dezhong; Xiaoyan, Zeng; Ko, Sung Kwon; Nah, Seung-Yeol; Kim, Hyoung-Chun; Shin, Eun-Joo
- Issue Date
- Aug-2023
- Publisher
- Elsevier Ltd
- Keywords
- Convulsive neurotoxicity; Ginsenoside Re; L-type calcium channel activator Bay k-8644; Mitochondrial dysfunction with altered redox status; Mouse hippocampus; Protein kinase Cδ gene
- Citation
- Food and Chemical Toxicology, v.178
- Journal Title
- Food and Chemical Toxicology
- Volume
- 178
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/70994
- DOI
- 10.1016/j.fct.2023.113869
- ISSN
- 0278-6915
1873-6351
- Abstract
- 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 Ca2+ channels. Here, we investigated whether ginsenoside Re (GRe) modulates excitotoxicity induced by the L-type Ca2+ 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 Ca2+ 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. © 2023 Elsevier Ltd
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