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Protective Effects of Paeoniflorin Against Glutamate-Induced Neurotoxicity in PC12 Cells via Antioxidant Mechanisms and Ca2+ Antagonism

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Abstract

Preclinical and clinical investigations have shown hippocampal neuronal atrophy and destruction were observed in patients with depression, which could be ameliorated by the treatment with antidepressants. Therefore, neuroprotection has been proposed to be one of the acting mechanisms of antidepressant. Paeoniflorin, a monoterpene glycoside, has been reported to display antidepressant-like effects in animal models of behavioral despair. The present study aimed to examine the protective effect of paeoniflorin on glutamate-induced neurotoxicity in cultured rat pheochromocytoma (PC12) cells. The results showed that pretreatment with paeoniflorin elevated cell viability, inhibited apoptosis, decreased levels of intracellular reactive oxygen species and malondialdehyde, and enhanced activity of superoxide dismutase in glutamate-treated PC12 cells. Pretreatment with paeoniflorin also reversed the increased intracellular Ca2+ concentration and the reduced Calbindin-D28K mRNA level caused by glutamate in PC12 cells. The results suggest that paeoniflorin exerts a neuroprotective effect on glutamate-induced neurotoxicity in PC12 cells, at least in part, via inhibiting oxidative stress and Ca2+ overload. This neuroprotective effect may be one of the action pathways accounting for the in vivo antidepressant activity of paeoniflorin.

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Acknowledgments

This study was supported by funding from the Zhejiang Provincial Program for the Cultivation of High-level Innovative Health talents (awarded to Professor Huang Zhen).

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Authors and Affiliations

  1. School of Chinese Medicine, The Chinese University of Hong Kong, Shatin, NT, Hong Kong, China

    Qing-Qiu Mao

  2. College of Pharmacy, Zhejiang Chinese Medicine University, Hangzhou, 310053, Zhejiang, China

    Xiao-Ming Zhong, Chun-Rong Feng, Ai-Juan Pan, Zhao-Yi Li & Zhen Huang

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  1. Qing-Qiu Mao
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  2. Xiao-Ming Zhong
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  3. Chun-Rong Feng
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  4. Ai-Juan Pan
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Correspondence to Qing-Qiu Mao or Zhen Huang.

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Mao, QQ., Zhong, XM., Feng, CR. et al. Protective Effects of Paeoniflorin Against Glutamate-Induced Neurotoxicity in PC12 Cells via Antioxidant Mechanisms and Ca2+ Antagonism. Cell Mol Neurobiol 30, 1059–1066 (2010). https://doi.org/10.1007/s10571-010-9537-5

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