Neural Regeneration Research ›› 2022, Vol. 17 ›› Issue (1): 178-184.doi: 10.4103/1673-5374.314321

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Polygalasaponin F protects hippocampal neurons against glutamate-induced cytotoxicity

Chong Sun1, Xin-Cheng Cao1, Zhi-Yang Liu1, Chao-Lin Ma1, Bao-Ming Li1, 2, *   

  1. 1Laboratory of Cognitive Function and Disorder, Institute of Life Science, Nanchang University, Nanchang, Jiangxi Province, China; 2Institute of Brain Science and Department of Psychology, School of Education, Hangzhou Normal University, Hangzhou, Zhejiang Province, China
  • Online:2022-01-05 Published:2021-09-22
  • Contact: Bao-Ming Li, PhD, bmli@ncu.edu.cn or bmli@hznu.edu.cn.
  • Supported by:
    This work was supported by the National Natural Science Foundation of China, Nos. 31971035 (to BML), 31771182 (to BML), 81471116 (to BML); and the Natural Science Foundation of Jiangxi Province of China, Nos. 20171BAB204019 (to CS), 20192ACB20022 (to CS).

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Abstract: 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.

Key words: BDNF, Ca2+ homeostasis, excitotoxicity, glutamate, hippocampal neurons, pCREB, polygalasaponin F, neuroprotection, NR2A, NR2B