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Protective effect of selaginellin on glutamate-induced cytotoxicity and apoptosis in differentiated PC12 cells

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Abstract

l-glutamate plays a key role in neuronal cell death associated with many neurodegenerative conditions such as cerebral ischemia, hypoxia, Alzheimer's, Huntington’s, and Parkinson’s diseases. Selaginellin, a component extracted from Saussurea pulvinata (Hook.et Grev.) Maximo, was assessed for its ability to protect rat pheochromocytoma (PC12) cells against oxidative toxicity induced by glutamate. The differentiated PC12 cells were pretreated with various concentrations (10−7, 3 × 10−7, or 10−6 M) of selaginellin for 1 h prior to exposure to l-glutamate. Selaginellin was shown to protect PC12 cells against glutamate toxicity, as determined by characteristic morphological features, lactate dehydrogenase release and cell viability, and apoptosis as evaluated by Hoechst 33342 staining assay and caspase-3 activity. In addition, the increase in levels of reactive oxygen species and decrease in klotho gene expression induced by glutamate were significantly reversed by selaginellin. Our study suggests that selaginellin has a neuroprotective effect against l-glutamate-induced neurotoxicity through mechanisms related to anti-oxidation and anti-apoptosis via scavenging reactive oxygen species and up-regulating the expression of klotho gene.

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Authors and Affiliations

  1. Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Changsha, 410078, China

    Chen-Jing Wang, Chang-Ping Hu, Qiong Yuan & Yuan-Jian Li

  2. Chemistry Section, Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Central South University, Changsha, 410013, China

    Kang-Ping Xu, Fu-Shuang Li, Hui Zou & Gui-Shan Tan

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  1. Chen-Jing Wang
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  2. Chang-Ping Hu
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Correspondence to Yuan-Jian Li.

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This study was supported by a grant from the National Natural Science Foundation of China (No. 30873149).

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Wang, CJ., Hu, CP., Xu, KP. et al. Protective effect of selaginellin on glutamate-induced cytotoxicity and apoptosis in differentiated PC12 cells. Naunyn-Schmied Arch Pharmacol 381, 73–81 (2010). https://doi.org/10.1007/s00210-009-0470-4

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  • DOI: https://doi.org/10.1007/s00210-009-0470-4

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