Prophylactic Neuroprotection of Total Glucosides of Paeoniae Radix Alba against Semen Strychni-Induced Neurotoxicity in Rats: Suppressing Oxidative Stress and Reducing the Absorption of Toxic Components.
Prophylactic Neuroprotection of Total Glucosides of Paeoniae Radix Alba against Semen Strychni-Induced Neurotoxicity in Rats: Suppressing Oxidative Stress and Reducing the Absorption of Toxic Components.
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白芍总苷对马钱子引起的大鼠神经毒性的预防性神经保护作用：抑制氧化应激并减少有毒成分的吸收
DOI：
10.3390/nu10040514
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发表时间：
2018-04-20
期刊：
影响因子：
5.9
通讯作者：
Chen X
中科院分区：
文献类型：
--
作者：
Li S;Chu Y;Zhang R;Sun L;Chen X
马钱子生物碱是中药马钱子的主要毒性成分，具有致命的神经毒性。因此，本研究旨在评价水杨酸的神经毒性及白芍总苷的预保护作用。首先建立SA脑损伤模型。通过生理和行为学测试、生化测定和组织学检查证实了SA的神经毒性和TGP的预保护作用。然后，液相色谱-串联质谱法被开发和验证，以调查的时间过程中的变化和分布士的宁和马钱子碱（两个主要的SA）在口服SA后，或没有TGP预处理。生化分析结果表明，白芍总苷能改善水杨酸引起的氧化应激状态。时程变化和分布研究表明，士的宁和马钱子碱被迅速吸收到脑中，早在0.5小时达到高峰，主要位于海马和小脑。白芍总苷通过减少毒性生物碱进入脑的吸收，对神经毒性表现出预保护作用。本研究结果可为今后马钱子神经毒性的研究和临床开发减轻马钱子神经毒性的中药提供有益的信息。
Strychnos alkaloids (SAs) are the main toxic constituents in Semen Strychni, a traditional Chinese medicine, which is known for its fatal neurotoxicity. Hence, the present study was carried out to evaluate the neurotoxicity induced by SAs and the pre-protective effects of the total glucosides of Paeoniae Radix Alba (TGP). An SA brain damage model was firstly established. The neurotoxicity induced by SAs and the pre-protective effects of TGP were confirmed by physical and behavioral testing, biochemical assay, and histological examination. Then, a liquid chromatography-tandem mass spectrometry method was developed and validated to investigate the time-course change and distribution of strychnine and brucine (two main SAs) in the brain after oral SA administration with or without TGP pretreatment. Biochemical analysis results indicated that TGP could ameliorate the oxidative stress status caused by SAs. Time-course change and distribution studies demonstrated that strychnine and brucine were rapidly absorbed into the brain, peaked early at 0.5 h, and were mainly located in the hippocampus and cerebellum. TGP showed a pre-protective effect against neurotoxicity by reducing the absorption of toxic alkaloids into the brain. These findings could provide beneficial information in facilitating future studies of Semen Strychni neurotoxicity and developing herbal medicines to alleviate neurotoxicity in the clinic.
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影响因子：
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