Liu Haolong, Qiu Feng, Yang Xinwei, Zhao Haiyu, Bian Baolin, Wang Lei
School of Traditional Chinese Medicine, Beijing Key Lab of TCM Collateral Disease Theory Research, Capital Medical University, Beijing 100069, China.
Beijing Institute For Drug Control, Beijing Key Laboratory of Analysis and Evaluation on Chinese Medicine, Beijing 100035, China.
Drug Des Devel Ther. 2019 Jul 16;13:2357-2370. doi: 10.2147/DDDT.S203874. eCollection 2019.
To determine the pharmacokinetic properties and pharmacological activity of the Yougui pill (YGP), which is a well-known Chinese medicine formula.
An ultra-performance liquid chromatography coupled with triple-quadrupole tandem mass spectrometry via electrospray ionization interface (UPLC-ESI-MS/MS) method was developed and validated for the simultaneous determination of several components in rat plasma. The method was then successfully applied to the pharmacokinetics of six bioactive components in experimental autoimmune encephalomyelitis (EAE) model rats after oral administration of YGP. The expression of cAMP response element binding protein (CREB) and growth-associated protein-43 (GAP-43) in SH-SY5Y cells treated with these six components, YGP extract, and YGP-containing serum were investigated to determine the pharmacodyamic material basis of YGP. Six bioactive components were detected in rat plasma, including songorine, benzoylhypaconitine, benzoylmesaconitine, neoline, karacoline and sweroside, which were rapidly absorbed after administration in EAE model rats.
The main pharmacokinetic parameters of six bioactive components were determined, and the constituents increased CREB and GAP-43 expressions in serum-deprived SH-SY5Y cells. The YGP-containing serum, six bioactive components, and YGP extract significantly increased the expression of both CREB and GAP-43 (<0.01), and there was no difference between the three groups.
The songorine, benzoylhypaconitine, benzoylmesaconitine, neoline, karacoline and sweroside were confirmed as the major bioactive components in YGP. The acquired data will be helpful for understanding the pharmacological and effective constituents of YGP.
确定著名中药方剂右归丸（YGP）的药代动力学特性和药理活性。
建立了一种超高效液相色谱-电喷雾电离接口串联三重四极杆质谱（UPLC-ESI-MS/MS）方法，并对其进行验证，用于同时测定大鼠血浆中的几种成分。该方法随后成功应用于口服YGP后实验性自身免疫性脑脊髓炎（EAE）模型大鼠体内六种生物活性成分的药代动力学研究。研究了用这六种成分、YGP提取物和含YGP血清处理的SH-SY5Y细胞中环磷酸腺苷反应元件结合蛋白（CREB）和生长相关蛋白43（GAP-43）的表达，以确定YGP的药效物质基础。在大鼠血浆中检测到六种生物活性成分，包括红古豆碱、苯甲酰次乌头碱、苯甲酰新乌头碱、新乌宁碱、卡拉可林和獐牙菜苷，它们在EAE模型大鼠给药后迅速被吸收。
测定了六种生物活性成分的主要药代动力学参数，这些成分增加了血清饥饿的SH-SY5Y细胞中CREB和GAP-43的表达。含YGP血清、六种生物活性成分和YGP提取物均显著增加了CREB和GAP-43的表达（<0.01），三组之间无差异。
红古豆碱、苯甲酰次乌头碱、苯甲酰新乌头碱、新乌宁碱、卡拉可林和獐牙菜苷被确认为YGP中的主要生物活性成分。所获得的数据将有助于理解YGP的药理和有效成分。
