Ginsenoside Re attenuates 8-OH-DPAT-induced serotonergic behaviors in mice via interactive modulation between PKCδ gene and Nrf2.
Eun-Joo ShinJi Hoon JeongBao-Trong NguyenNaveen SharmaCuong Ngoc Kim TranSeung-Yeol NahYi LeeJae Kyung ByunSung Kwon KoHyoung-Chun KimPublished in: Drug and chemical toxicology (2022)
It has been recognized that serotonergic blocker showed serious side effects, and that ginsenoside modulated serotonergic system with the safety. However, the effects of ginsenoside on serotonergic impairments remain to be clarified. Thus, we investigated ginsenoside Re (GRe), a major bioactive component in the mountain-cultivated ginseng on (±)-8-hydroxy-dipropylaminotetralin (8-OH-DPAT), a 5-HT 1A receptor agonist. In the present study, we observed that the treatment with GRe resulted in significant inhibition of protein kinase C δ (PKCδ) phosphorylation induced by the 5-HT 1A receptor agonist (±)-8-hydroxy-dipropylaminotetralin (8-OH-DPAT) in the hypothalamus of the wild-type (WT) mice. The inhibition of GRe was comparable with that of the PKCδ inhibitor rottlerin or the 5-HT 1A receptor antagonist WAY100635 (WAY). 8-OH-DPAT-induced significant reduction in nuclear factor erythroid-2-related factor 2 (Nrf2)-related system (i.e., Nrf2 DNA binding activity, γ-glutamylcysteine ligase modifier (GCLm) and γ-glutamylcysteine ligase catalytic (GCLc) mRNA expression, and glutathione (GSH)/oxidized glutathione (GSSG) ratio) was significantly attenuated by GRe, rottlerin, or WAY in WT mice. However, PKCδ gene knockout significantly protected the Nrf2-dependent system from 8-OH-DPAT insult in mice. Increases in 5-hydroxytryptophan (5-HT) turnover rate, overall serotonergic behavioral score, and hypothermia induced by 8-OH-DPAT were significantly attenuated by GRe, rottlerin, or WAY in WT mice. Consistently, PKCδ gene knockout significantly attenuated these parameters in mice. However, GRe or WAY did not provide any additional positive effects on the serotonergic protective potential mediated by PKCδ gene knockout in mice. Therefore, our results suggest that PKCδ is an important mediator for GRe-mediated protective activity against serotonergic impairments/oxidative burden caused by the 5-HT 1A receptor.
Keyphrases
- type diabetes
- wild type
- protein kinase
- high fat diet induced
- oxidative stress
- nuclear factor
- copy number
- genome wide
- cardiac arrest
- gene expression
- high resolution
- risk assessment
- dna methylation
- mass spectrometry
- genome wide identification
- skeletal muscle
- transcription factor
- body composition
- binding protein
- single molecule
- angiotensin ii
- endothelial cells
- fluorescent probe
- angiotensin converting enzyme
- atomic force microscopy
- replacement therapy