Pharmacokinetic behavior and brain tissue distribution of paeoniflorin combined with normal and toxic doses of strychnine in rats after percutaneous administration / 中国中药杂志

This study aims to establish a rapid and sensitive UPLC-MS/MS method for simultaneously determining the content of strychnine and paeoniflorin in plasma and brain tissue of rats, and compare the pharmacokinetic behavior and brain tissue distribution of paeoniflorin combined with normal and toxic doses of strychnine in rats after percutaneous administration. Compared with those in the toxic-dose strychnine group, the AUC_(0-t), AUC_(0-∞), and C_(max) of strychnine decreased by 51.51%, 45.68%, and 46.03%, respectively(P<0.01), and the corresponding values of paeoniflorin increased by 91.41%, 102.31%, and 169.32%, respectively(P<0.01), in the compatibility group. Compared with the normal-dose strychnine group, the compatibility group showed insignificantly decreased C_(max), AUC_(0-t), and AUC_(0-∞) of strychnine, increased C_(max) and T_(max) of paeoniflorin(P<0.01), 66.88% increase in AUC_(0-t), and 70.55% increase in AUC_(0-∞) of paeoniflorin. In addition, the brain tissue concentration of strychnine decreased and that of paeoniflorin increased after compatibility. The combination of paeoniflorin with normal dose and toxic dose of strychnine can inhibit the percutaneous absorption of strychnine, and greatly promote the percutaneous penetration of paeoniflorin, whereas the interaction mechanism remains to be explored. The UPLC-MS/MS method established in this study is easy to operate and has good precision. It is suitable for in vivo study of pharmacokinetic behavior and brain tissue distribution of paeoniflorin and strychnine after percutaneous administration in rats, which provides reference for the safe and rational clinical use of strychnine and the combined use of drugs, and lays a solid foundation for the development of external preparations containing Strychni Semen.

Distribution characteristics of nine main components of Huanglian Jiedu Decoction in rat brain / 中草药

Objective: To establish a sensitive, accurate and reliable LC-MS-MS analysis method for the nine major components (berberine, berberrubine, jatrorrhizine, palmatine, baicalin, wogonin, oroxylin A, geniposide and gardenin B) in Huanglian Jiedu Decoction (HJD) in rat hippocampus, cortex, striatum, and cerebrospinal fluid, and to study the distribution characteristics of the components in brain tissues of rats. Methods: The mass spectrometry detection conditions and chromatographic analysis conditions of nine main components and internal standards (clarithromycin and chloramphenicol) was optimized, and then the methodological investigations were performed. After HJD was administrated for 1 h, the samples of cerebrospinal fluid, hippocampus, cortex and striatum tissues were collected, and the contents of nine components in these samples were measured. Results: Berberine, jatrorrhizine, palmatine, baicalin, wogonin, oroxylin A and gardenin B showed a good linear relationship in the range of 1-250 ng/mL (r2 > 0.99). Berberrubine had a good linear relationship in the range of 1-500 ng/mL (r2 = 0.991 2), and geniposide had a good linear relationship in the range of 5-500 ng/mL, respectively (r2 = 0.999 5). The intra-day and inter-day precision of each component was less than 12.94%, the accuracy was from -12.71% to 6.91%; The extraction recovery rate was from 88.02% to 106.7%; The matrix effect was from 88.92% to 105.10%; And the short-term, freeze-thaw cycle and long-term stability were less than 12.51%. The content of each component in the hippocampus, cortex and striatum was berberine > baicalin > geniposide > berberrubine > palmatine > wogonin > jatrorrhizine > oroxylin A > gardenin B; And the content of each component in cerebrospinal fluid was geniposide > berberine > berberrubine > palmatine > baicalin> gardenin B > jatrorrhizine > wogonin > oroxylin A. Conclusion: The method can be used for the simultaneous detection of the concentration of nine active components in brain tissues of rats, and successfully applied to the study of brain tissue distribution, which provides a reference for HJD to treat brain diseases.

Study on brain tissue distribution of compatibility of Yuanhu Zhitong Prescription in rat based on Q-marker / 中草药

Objective To investigate the effect of compatibility on brain tissue distribution in rat of corydaline, tetrahydropalmatine, protopine, imperatorin and isoimperatorin in Corydalis Rhizoma and Angelicae Dahuricae Radix, and to provide further experimental evidence for confirming the Q-marker of Yuanhu Zhitong Prescription. Methods After oral administration of Corydalis Rhizoma, Angelicae Dahuricae Radix, and Yuanhu Zhitong Prescription extracts respectively, the concentration of five compounds in brain tissue samples at different time points was determined by UPLC-MS/MS, and the effect of compatibility on brain tissue distribution was further evaluated by kinetic parameters. Results Compared with single-herb group, AUC and Cmax of corydaline, tetrahydropalmatine and protopine in Yuanhu Zhitong Prescription group were increased significantly, and MRT of imperatorin and isoimperatorin were prolonged at the same time. Conclusion Corydalis Rhizoma and Angelicae Dahuricae Radix exist synergistic effect, the compatibility of these two herbs promote brain tissue distribution of corydaline, tetrahydropalmatine, protopine, imperatorin and isoimperatorin, which can be used as Q-marker of Yuanhu Zhitong Prescription.