Biopharmaceutics, NMPA Key Laboratory for Research and Evaluation of Drug Metabolism, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, China.
Changsha Research and Development Center On Obstetric and Gynecologic Traditional Chinese Medicine Preparation, NHC Key Laboratory of Birth Defects Research, Prevention and Treatment, Hunan Provincial Maternal and Child Health Care Hospital, Changsha, 410008, Hunan, China.
BMC Complement Med Ther. 2022 Dec 6;22(1):323. doi: 10.1186/s12906-022-03784-x.
Penyanqing (PYQ), a traditional Chinese medicine (TCM), has a good clinical efficacy for the treatment of pelvic inflammatory disease (PID). Previously, researches on its anti-inflammatory effect and mechanism in vitro, in silico, and in vivo have been reported by our team. However, the interrelationship between the anti-inflammatory activity and the active compounds in PYQ are not clear. Here, the pharmacokinetics-pharmacodynamics (PK-PD) study was carried out for more proper clinical use.
The plasma concentrations of salvianolic acid B (SAB), protocatechualdehyde (PRO), paeoniflorin (PE), astilbin (AST), ferulic acid (FE), and chlorogenic acid (CH) in SD rats after PYQ administration were determined by a selective and rapid HPLC-MS/MS method. In addition, the PK-PD on cell model was used to explore the relationship between the plasma concentration and inflammatory biomarkers (TNF-α, IL-1β).
The results of this study showed that the six components could reach the peak blood concentration within 0.29 h, indicating the rapid absorption of it. The eliminations of AST, CH, FE, PE, and PRO were relatively fast due to their mean residence times (MRTs) within 3 h, while the elimination of SAB was slower (MRT 5.67 ± 0.66 h). Combined with a THP-1 cell model, there was a significant correlation between inflammatory factors and component plasma concentrations with correlation coefficients in the range of -0.9--0.746. Correspondingly, the drug-containing plasma obtained at 0.25 h point exhibited the best inhibition effect on production of IL-1β and TNF-α in LPS-induced THP-1 cells.
The six main components in PYQ could be quickly absorbed, and there was a potential good correlation between their pharmacokinetics and the pharmacodynamics of PYQ.
盆腔炎清方（PYQ）是一种治疗盆腔炎（PID）的中药，具有良好的临床疗效。此前，我们团队已经报道了其在体外、计算和体内的抗炎作用和机制的研究。然而，PYQ 的抗炎活性与其活性化合物之间的相互关系尚不清楚。在这里，进行了药代动力学-药效学（PK-PD）研究，以更恰当地进行临床应用。
采用选择性和快速的 HPLC-MS/MS 方法测定 SD 大鼠给予 PYQ 后血浆中丹酚酸 B（SAB）、原儿茶醛（PRO）、芍药苷（PE）、马钱苷（AST）、阿魏酸（FE）和绿原酸（CH）的浓度。此外，还使用细胞模型进行了 PK-PD 研究，以探讨血浆浓度与炎症生物标志物（TNF-α、IL-1β）之间的关系。
本研究结果表明，这六种成分可在 0.29 h 内达到血药峰浓度，表明其吸收迅速。AST、CH、FE、PE 和 PRO 的消除较快，因为它们的平均驻留时间（MRT）在 3 h 内，而 SAB 的消除较慢（MRT 5.67±0.66 h）。结合 THP-1 细胞模型，炎症因子与成分血浆浓度之间存在显著相关性，相关系数在-0.9 到-0.746 之间。相应地，在 LPS 诱导的 THP-1 细胞中，在 0.25 h 点获得的含药血浆对 IL-1β和 TNF-α的产生表现出最佳的抑制作用。
PYQ 中的六种主要成分能够快速吸收，其药代动力学与 PYQ 的药效学之间存在潜在的良好相关性。
