Zhao Xixi, Yu Li, Chen Yulin, Wang Yu, Wan Haitong, Yang Jiehong
College of Life Science, Zhejiang Chinese Medical University, Hangzhou, China.
College of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, China.
Front Pharmacol. 2020 Jan 24;10:1598. doi: 10.3389/fphar.2019.01598. eCollection 2019.
In China, the combination of herb (Danshen) and . (Honghua) is an effective treatment for stroke. A previous study showed that the combination of four herbal components: danshensu (DSS), hydroxysafflor yellow A (HSYA), salvianolic acid A (SAA), and salvianolic acid B (SAB) was effective for treatment of cerebral ischemia-reperfusion (I/R) injury in rats. However, the pharmacokinetic characteristics of this formula require further investigation. The present study investigated the pharmacokinetic differences between each component of in two formulas in cerebral I/R injury rats. The influencing factors may affect the compatibility of components were analyzed.
Focal cerebral I/R was induced by middle cerebral artery occlusion (MCAO). Rats that underwent MCAO were randomly divided into two groups and administered treatments through the tail vein. Blood samples were collected at predetermined time points following administration. The concentrations of DSS, HSYA, SAB, and SAA in rat plasma were determined using HPLC-DAD, and the main pharmacokinetic parameters were calculated. Pharmacokinetic parameters were calculated using DAS 3.2.6 software and SPSS 23.0 statistical analysis software.
Our results showed that DSS, HSYA, SAB, and SAA in MCAO model rats had statistically significant differences in two formulas. For DSS and SAA, pharmacokinetic parameters with statistically significant differences including AUC, AUMC, MRT, VRT, t, V, CL, and C ( < 0.01). For HSYA, significant differences in the parameters including AUC, AUMC, MRT, VRT ( 0.01), CL and C ( 0.05).
The difference in pharmacokinetic parameters in response to each component may have been due to differences in the dosages of the components (HSYA, SAA, SAB) and the compatibility of components. Meanwhile, there were many influencing factors could affect the compatibility of components, such as the metabolism by CYP450 enzymes, plasma protein binding rates, and effects related to the blood-brain barrier (BBB). Moreover, our study provided new insights, such as choosing appropriate dosages of active components of traditional Chinese medicine (TCM) to aid in prevention and treatment of cerebral ischemic diseases. The method and results in this study could provide a foundation for future pharmacological studies of the active components in Danshen and Honghua.
在中国，草药（丹参）和（红花）的组合是治疗中风的有效方法。先前的一项研究表明，四种草药成分：丹参素（DSS）、羟基红花黄色素A（HSYA）、丹酚酸A（SAA）和丹酚酸B（SAB）的组合对治疗大鼠脑缺血再灌注（I/R）损伤有效。然而，该配方的药代动力学特征需要进一步研究。本研究调查了两种配方中各成分在脑I/R损伤大鼠中的药代动力学差异。分析了可能影响成分配伍的影响因素。
通过大脑中动脉闭塞（MCAO）诱导局灶性脑I/R。接受MCAO的大鼠随机分为两组，通过尾静脉给药。给药后在预定时间点采集血样。采用HPLC-DAD法测定大鼠血浆中DSS、HSYA、SAB和SAA的浓度，并计算主要药代动力学参数。使用DAS 3.2.6软件和SPSS 23.0统计分析软件计算药代动力学参数。
我们的结果表明，MCAO模型大鼠中DSS、HSYA、SAB和SAA在两种配方中有统计学显著差异。对于DSS和SAA，具有统计学显著差异的药代动力学参数包括AUC、AUMC、MRT、VRT、t、V、CL和C（<0.01）。对于HSYA，参数中的显著差异包括AUC、AUMC、MRT、VRT（0.01）、CL和C（0.05）。
各成分药代动力学参数的差异可能是由于成分（HSYA、SAA、SAB）剂量和成分配伍的差异。同时，有许多影响因素会影响成分的配伍，如CYP450酶的代谢、血浆蛋白结合率以及与血脑屏障（BBB）相关的影响。此外，我们的研究提供了新的见解，如选择合适剂量的中药活性成分以辅助预防和治疗脑缺血性疾病。本研究的方法和结果可为今后丹参和红花活性成分的药理学研究提供基础。
