School of Pharmacy, Shenyang Pharmaceutical University, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang 110000, China.
School of Traditional Chinese Material Medica, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang 110000, China.
Nutrients. 2018 Apr 20;10(4):514. doi: 10.3390/nu10040514.
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.
马钱子生物碱（SAs）是马钱子这一传统中药中的主要毒性成分，其具有致命的神经毒性。因此，本研究旨在评估 SAs 诱导的神经毒性和白芍总苷（TGP）的预先保护作用。首先建立了 SAs 脑损伤模型。通过物理和行为测试、生化测定和组织学检查，证实了 SAs 诱导的神经毒性和 TGP 的预先保护作用。然后，建立并验证了一种液相色谱-串联质谱法，以研究口服 SAs 给药后（或不给予 TGP 预处理），马钱子碱和士的宁（两种主要 SAs）在脑内的时程变化和分布。生化分析结果表明，TGP 可以改善 SAs 引起的氧化应激状态。时程变化和分布研究表明，马钱子碱和士的宁迅速被吸收到大脑中，在 0.5 小时时早期达到峰值，主要位于海马体和小脑。TGP 通过减少有毒生物碱进入大脑的吸收，表现出对神经毒性的预先保护作用。这些发现可为未来研究马钱子的神经毒性和开发草药以减轻临床神经毒性提供有益信息。
