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佐剂性关节炎大鼠关节腔透析液和血液透析液中1-磷酸鞘氨醇的超高效液相色谱-串联质谱分析:在栀子苷药效学研究中的应用

UHPLC-MS/MS analysis of sphingosine 1-phosphate in joint cavity dialysate and hemodialysis solution of adjuvant arthritis rats: Application to geniposide pharmacodynamic study.

作者信息

Xuejing Dai, Wenyu Wang, Hong Wu, Zhengrong Zhang, Li Dai, Jun Fu, Ran Deng, Feng Li, Yan Wang, Xiang Zhan

机构信息

Anhui University of Chinese Medicine, Hefei, China.

Anhui Province Key Laboratory of Xin'an Medicine, Ministry of Education, Hefei, China.

出版信息

Biomed Chromatogr. 2019 Jul;33(7):e4526. doi: 10.1002/bmc.4526. Epub 2019 Mar 21.

DOI:10.1002/bmc.4526
PMID:30834567
Abstract

Geniposide (GE) is an iridoid glycoside compound with anti-inflammatory effect. The potential of sphingosine 1-phosphate (S1P) as a plasma marker in human diseases was suggested recently in the literature, which demonstrated that, in patients with inflammatory diseases, plasma S1P was elevated. It follows that the obstructive coronary artery disease can be predicted with serum S1P. Therefore, S1P can also be potentially used as a pharmacodynamic marker to study adjuvant arthritis (AA) rats. In the current study, a UHPLC-MS/MS method combined with the microdialysis sampling technique (using FTY720 phosphate as an internal standard) was adopted and validated to measure S1P levels in the hemodialysis fluid and joint cavity dialysates of AA rats after oral administration of GE. A S1P concentration-time curve in the dialysate was established in this study. It was demonstrated that GE exerted an anti-inflammatory effect by reducing AA-induced elevated S1P levels. It is showed that changes in S1P concentrations over time can be used to monitor the pharmacodynamic effects of GE in treating AA rats in pharmacodynamic studies.

摘要

栀子苷(GE)是一种具有抗炎作用的环烯醚萜苷类化合物。近期文献表明,1-磷酸鞘氨醇(S1P)作为人类疾病血浆标志物具有潜在价值,该文献指出,在炎症性疾病患者中,血浆S1P水平升高。由此可见,阻塞性冠状动脉疾病可用血清S1P进行预测。因此,S1P也有可能用作研究佐剂性关节炎(AA)大鼠的药效学标志物。在本研究中,采用并验证了一种超高效液相色谱-串联质谱法(UHPLC-MS/MS)结合微透析采样技术(使用FTY720磷酸盐作为内标)来测定口服GE后AA大鼠血液透析液和关节腔透析液中的S1P水平。本研究建立了透析液中S1P浓度-时间曲线。结果表明,GE通过降低AA诱导升高的S1P水平发挥抗炎作用。结果表明,在药效学研究中,S1P浓度随时间的变化可用于监测GE治疗AA大鼠的药效学作用。

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Anti-Inflammatory Effect of Geniposide on Regulating the Functions of Rheumatoid Arthritis Synovial Fibroblasts via Inhibiting Sphingosine-1-Phosphate Receptors1/3 Coupling Gαi/Gαs Conversion.栀子苷通过抑制1-磷酸鞘氨醇受体1/3偶联Gαi/Gαs转换对类风湿关节炎滑膜成纤维细胞功能的调节作用及抗炎效应
Front Pharmacol. 2020 Dec 8;11:584176. doi: 10.3389/fphar.2020.584176. eCollection 2020.