Protective Effects of Paeoniflorin Against Glutamate-Induced Neurotoxicity in PC12 Cells via Antioxidant Mechanisms and Ca2+ Antagonism
Protective Effects of Paeoniflorin Against Glutamate-Induced Neurotoxicity in PC12 Cells via Antioxidant Mechanisms and Ca2+ Antagonism
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DOI：
10.1007/s10571-010-9537-5
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发表时间：
2010-10-01
影响因子：
4
通讯作者：
Huang, Zhen
中科院分区：
文献类型：
--
作者：
Mao, Qing-Qiu;Zhong, Xiao-Ming;Huang, Zhen
临床前和临床研究表明，抑郁症患者存在海马神经元萎缩和破坏，抗抑郁药物治疗可改善海马神经元萎缩和破坏。因此，神经保护被认为是抗抑郁药的作用机制之一。芍药苷是一种单萜糖苷，据报道在行为绝望的动物模型中显示出抗抑郁样作用。本研究旨在探讨芍药苷对谷氨酸诱导的大鼠嗜铬细胞瘤（PC 12）细胞神经毒性的保护作用。结果表明，芍药苷预处理提高细胞活力，抑制细胞凋亡，降低细胞内活性氧和丙二醛的水平，提高谷氨酸处理的PC 12细胞超氧化物歧化酶的活性。芍药苷预处理还可逆转谷氨酸引起的PC 12细胞内Ca ~（2+）浓度升高和Calbindin-D28 K mRNA水平降低。结果表明，芍药苷对谷氨酸诱导的PC 12细胞神经毒性具有神经保护作用，至少部分是通过抑制氧化应激和钙超载。这种神经保护作用可能是芍药苷体内抗抑郁活性的作用途径之一。
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.