Polygalasaponin F protects hippocampal neurons against glutamate-induced cytotoxicity

Excess extracellular glutamate leads to excitotoxicity, which induces neuronal death through the overactivation of N-methyl-D-aspartate receptors (NMDARs). Excitotoxicity is thought to be closely related to various acute and chronic neurological disorders, such as stroke and Alzheimer’s disease. Pol...

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Main Authors: Chong Sun, Xin-Cheng Cao, Zhi-Yang Liu, Chao-Lin Ma, Bao-Ming Li
Format: Article
Language:English
Published: Wolters Kluwer Medknow Publications 2022-01-01
Series:Neural Regeneration Research
Subjects:
Online Access:http://www.nrronline.org/article.asp?issn=1673-5374;year=2022;volume=17;issue=1;spage=178;epage=184;aulast=Sun
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author Chong Sun
Xin-Cheng Cao
Zhi-Yang Liu
Chao-Lin Ma
Bao-Ming Li
author_facet Chong Sun
Xin-Cheng Cao
Zhi-Yang Liu
Chao-Lin Ma
Bao-Ming Li
author_sort Chong Sun
collection DOAJ
description Excess extracellular glutamate leads to excitotoxicity, which induces neuronal death through the overactivation of N-methyl-D-aspartate receptors (NMDARs). Excitotoxicity is thought to be closely related to various acute and chronic neurological disorders, such as stroke and Alzheimer’s disease. Polygalasaponin F (PGSF) is a triterpenoid saponin monomer that can be isolated from Polygala japonica, and has been reported to protect cells against apoptosis. To investigate the mechanisms underlying the neuroprotective effects of PGSF against glutamate-induced cytotoxicity, PGSF-pretreated hippocampal neurons were exposed to glutamate for 24 hours. The results demonstrated that PGSF inhibited glutamate-induced hippocampal neuron death in a concentration-dependent manner and reduced glutamate-induced Ca2+ overload in the cultured neurons. In addition, PGSF partially blocked the excess activity of NMDARs, inhibited both the downregulation of NMDAR subunit NR2A expression and the upregulation of NMDAR subunit NR2B expression, and upregulated the expression of phosphorylated cyclic adenosine monophosphate-responsive element-binding protein and brain-derived neurotrophic factor. These findings suggest that PGSF protects cultured hippocampal neurons against glutamate-induced cytotoxicity by regulating NMDARs. The study was approved by the Institutional Animal Care Committee of Nanchang University (approval No. 2017-0006) on December 29, 2017.
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spelling doaj.art-30c279d255ef42a483bb4456dd7b3d822022-12-21T18:26:17ZengWolters Kluwer Medknow PublicationsNeural Regeneration Research1673-53742022-01-0117117818410.4103/1673-5374.314321Polygalasaponin F protects hippocampal neurons against glutamate-induced cytotoxicityChong SunXin-Cheng CaoZhi-Yang LiuChao-Lin MaBao-Ming LiExcess extracellular glutamate leads to excitotoxicity, which induces neuronal death through the overactivation of N-methyl-D-aspartate receptors (NMDARs). Excitotoxicity is thought to be closely related to various acute and chronic neurological disorders, such as stroke and Alzheimer’s disease. Polygalasaponin F (PGSF) is a triterpenoid saponin monomer that can be isolated from Polygala japonica, and has been reported to protect cells against apoptosis. To investigate the mechanisms underlying the neuroprotective effects of PGSF against glutamate-induced cytotoxicity, PGSF-pretreated hippocampal neurons were exposed to glutamate for 24 hours. The results demonstrated that PGSF inhibited glutamate-induced hippocampal neuron death in a concentration-dependent manner and reduced glutamate-induced Ca2+ overload in the cultured neurons. In addition, PGSF partially blocked the excess activity of NMDARs, inhibited both the downregulation of NMDAR subunit NR2A expression and the upregulation of NMDAR subunit NR2B expression, and upregulated the expression of phosphorylated cyclic adenosine monophosphate-responsive element-binding protein and brain-derived neurotrophic factor. These findings suggest that PGSF protects cultured hippocampal neurons against glutamate-induced cytotoxicity by regulating NMDARs. The study was approved by the Institutional Animal Care Committee of Nanchang University (approval No. 2017-0006) on December 29, 2017.http://www.nrronline.org/article.asp?issn=1673-5374;year=2022;volume=17;issue=1;spage=178;epage=184;aulast=Sunbdnf; ca2+ homeostasis; excitotoxicity; glutamate; hippocampal neurons; pcreb; polygalasaponin f; neuroprotection; nr2a; nr2b
spellingShingle Chong Sun
Xin-Cheng Cao
Zhi-Yang Liu
Chao-Lin Ma
Bao-Ming Li
Polygalasaponin F protects hippocampal neurons against glutamate-induced cytotoxicity
Neural Regeneration Research
bdnf; ca2+ homeostasis; excitotoxicity; glutamate; hippocampal neurons; pcreb; polygalasaponin f; neuroprotection; nr2a; nr2b
title Polygalasaponin F protects hippocampal neurons against glutamate-induced cytotoxicity
title_full Polygalasaponin F protects hippocampal neurons against glutamate-induced cytotoxicity
title_fullStr Polygalasaponin F protects hippocampal neurons against glutamate-induced cytotoxicity
title_full_unstemmed Polygalasaponin F protects hippocampal neurons against glutamate-induced cytotoxicity
title_short Polygalasaponin F protects hippocampal neurons against glutamate-induced cytotoxicity
title_sort polygalasaponin f protects hippocampal neurons against glutamate induced cytotoxicity
topic bdnf; ca2+ homeostasis; excitotoxicity; glutamate; hippocampal neurons; pcreb; polygalasaponin f; neuroprotection; nr2a; nr2b
url http://www.nrronline.org/article.asp?issn=1673-5374;year=2022;volume=17;issue=1;spage=178;epage=184;aulast=Sun
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AT xinchengcao polygalasaponinfprotectshippocampalneuronsagainstglutamateinducedcytotoxicity
AT zhiyangliu polygalasaponinfprotectshippocampalneuronsagainstglutamateinducedcytotoxicity
AT chaolinma polygalasaponinfprotectshippocampalneuronsagainstglutamateinducedcytotoxicity
AT baomingli polygalasaponinfprotectshippocampalneuronsagainstglutamateinducedcytotoxicity