Pharmacokinetics and dopamine/acetylcholine releasing effects of ginsenoside Re in hippocampus and mPFC of freely moving rats
Pharmacokinetics and dopamine/acetylcholine releasing effects of ginsenoside Re in hippocampus and mPFC of freely moving rats
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DOI：
10.1038/aps.2012.147
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发表时间：
2013-02-01
影响因子：
8.2
通讯作者：
Li, Ke-xin
中科院分区：
文献类型：
--
作者：
Shi, Jing;Xue, Wei;Li, Ke-xin
目的：研究人参皂苷Re(Re)在学习记忆相关脑区的药代动力学和多巴胺/乙酰胆碱释放作用，阐明其抗痴呆作用的神经化学机制。方法：在清醒、自由活动的雄性SD大鼠海马区、内侧前额叶皮质(MPFC)和第三脑室植入透析探针，进行微透析。用LC-MS/MS法测定透析液中Re、多巴胺(DA)和乙酰胆碱(ACh)的浓度。结果：单次皮下注射Re(12.5、25和50 mg/kg)后，Re迅速分布到脑脊液中，并呈线性药动学关系。各剂量的峰值浓度(C-max)均出现在60min。低剂量(12.5 mg/kg)透析240min后未检出Re。结论：Re的药代动力学和药效学联合研究表明，Re可增加细胞外尤其是海马区DA和ACh的水平，至少部分参与了Re的抗痴呆作用。
Aim: To investigate the pharmacokinetics and dopamine/acetylcholine-releasing effects of ginsenoside Re (Re) in brain regions related to learning and memory, and to clarify the neurochemical mechanisms underlying its anti-dementia activity.Methods: Microdialysis was conducted on awake, freely moving adult male SD rats with dialysis probes implanted into the hippocampus', medial prefrontal cortex (mPFC) or the third ventricle. The concentrations of Re, dopamine (DA) and acetylcholine (ACh) in dialysates were determined using LC-MS/MS.Results: Subcutaneous administration of a single dose of Re (12.5, 25 or 50 mg/kg) rapidly distributed to the cerebrospinal fluid and exhibited linear pharmacokinetics. The peak concentration (C-max) occurred at 60 min for all doses. Re was not detectable after 240 min in the dialysates for the low dose of 12.5 mg/kg. At the same time, Re dose-dependently increased extracellular levels of DA and ACh in the hippocampus and mPFC, and more prominent effects were observed in the hippocampus.Conclusion: The combined study of the pharmacokinetics and pharmacodynamics of Re demonstrate that increase of extracellular levels of DA and ACh, particularly in the hippocampus, may contribute, at least in part, to the anti-dementia activity of Re.