Mechanism of Total Glucosides of Paeony in Attenuating Neurotoxicity of Aqueous Extract of Strychni Semen via GRIN2A/PLCB1/PRKCG Signaling Pathway
10.13422/j.cnki.syfjx.20250395
- VernacularTitle:基于GRIN2A/PLCB1/PRKCG信号通路探讨白芍总苷减轻马钱子水提物神经损伤的作用机制
- Author:
Siyu LI
1
;
Kun YANG
1
;
Changyue SONG
1
;
Peiping CHEN
1
;
Xinzhuo ZHANG
1
;
Mingzhu QI
1
;
Xiaohui SU
1
;
Xiangying KONG
1
Author Information
1. Institute of Chinese Materia Media，China Academy of Chinese Medical Science，Beijing 100700，China
- Publication Type:Journal Article
- Keywords:
aqueous extract of Strychni Semen;
total glucosides of paeony;
neurotoxicity;
formulation to reduce toxicity;
glutamate receptor，ionotropic， N-methyl-D-aspartate 2a （GRIN2A）/phospholipase C β1 （PLCB1）/protein kinase C， gamma （PRKCG） signaling pathway
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2024;30(23):56-63
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo investigate the effect of total glucosides of paeony （TGP） on neurotoxicity induced by aqueous extract of Strychni Semen （SA） in mice and to explore its mechanism. MethodThirty-two male KM mice were randomly divided into normal group，SA group （19.5 mg·kg-1），TGP group （225 mg·kg-1），and SA+TGP group （SA 19.5 mg·kg-1+TGP 225 mg·kg-1）. The open field test and beam walking test were used to observe the behavioral changes in mice. Pathological changes in the Nissl bodies of the cerebral cortex were assessed through Nissl staining. The levels of malondialdehyde （MDA），glutamate （Glu） in the mouse brain tissue，and serum levels of 5-hydroxytryptamine （5-HT） were detected using enzyme-linked immunosorbent assay （ELISA）. Transcriptome sequencing was employed to analyze gene expression profiles in the brain tissue. Common differentially expressed genes （DEGs） underwent gene ontology （GO） and kyoto encyclopedia of genes and genomes （KEGG） enrichment analyses. The mRNA expression levels of key targets were determined using quantitative real-time polymerase chain reaction （Real-time PCR）. ResultCompared with the normal group，the SA group exhibited significant increases in side-to-side distance and average speed in the open field test，as well as increased walking time on the balance beam. The axons of cortical neurons were absent，and the levels of Glu and MDA in the brain tissue were significantly elevated （P<0.05，P<0.01），along with a notable increase in serum 5-HT levels （P<0.05）. In contrast to the SA group，the SA+TGP group significantly reduced the side-to-side distance，average speed，and balance beam walking time （P<0.05 or P<0.01）. The neuronal axons were clearly visible，and levels of 5-HT，Glu，and MDA were decreased （P<0.05，P<0.01）. Transcriptome analysis indicated that TGP could regulate the glutamate receptor，ionotropic，N-methyl-D-aspartate 2a （GRIN2A）/phospholipase C β1 （PLCB1）/protein kinase C，gamma （PRKCG） signaling pathway. Compared with the normal group，SA significantly decreased the expression of GRIN2A，PLCB1，and PRKCG genes in the mouse brain （P<0.01），while the mRNA levels of GRIN2A and PRKCG significantly increased after TGP administration （P<0.05，P<0.01）. ConclusionSA induces significant neurotoxicity in the mouse brain，and TGP significantly alleviates SA-induced neurological damage，potentially through the GRIN2A/PLCB1/PRKCG signaling pathway.
