Spiess Deborah, Abegg Vanessa Fabienne, Chauveau Antoine, Rath Joshua, Treyer Andrea, Reinehr Michael, Kuoni Sabrina, Oufir Mouhssin, Potterat Olivier, Hamburger Matthias, Simões-Wüst Ana Paula
Department of Obstetrics, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
Division of Pharmaceutical Biology, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland.
Front Pharmacol. 2023 Mar 31;14:1123194. doi: 10.3389/fphar.2023.1123194. eCollection 2023.
Safe medications for mild mental diseases in pregnancy are needed. Phytomedicines from St. John's wort and valerian are valid candidates, but safety data in pregnancy are lacking. The transplacental transport of hyperforin and hypericin (from St. John's wort), and valerenic acid (from valerian) was evaluated using the cotyledon perfusion model (4 h perfusions, term placentae) and, in part, the Transwell assay with BeWo b30 cells. Antipyrine was used for comparison in both models. U(H)PLC-MS/MS bioanalytical methods were developed to quantify the compounds. Perfusion data obtained with term placentae showed that only minor amounts of hyperforin passed into the fetal circuit, while hypericin did not cross the placental barrier and valerenic acid equilibrated between the maternal and fetal compartments. None of the investigated compounds affected metabolic, functional, and histopathological parameters of the placenta during the perfusion experiments. Data from the Transwell model suggested that valerenic acid does not cross the placental cell layer. Taken together, our data suggest that throughout the pregnancy the potential fetal exposure to hypericin and hyperforin - but not to valerenic acid - is likely to be minimal.
孕期治疗轻度精神疾病的安全药物很有必要。来自圣约翰草和缬草的植物药是有效的候选药物,但缺乏孕期安全性数据。使用子叶灌注模型(4小时灌注,足月胎盘)并部分采用BeWo b30细胞的Transwell试验,评估了金丝桃素和金丝桃苷(来自圣约翰草)以及缬草烯酸(来自缬草)的经胎盘转运情况。在两个模型中均使用安替比林作为对照。开发了超高效液相色谱-串联质谱(U(H)PLC-MS/MS)生物分析方法来定量这些化合物。足月胎盘获得的灌注数据表明,只有少量金丝桃素进入胎儿循环,而金丝桃苷未穿过胎盘屏障,缬草烯酸在母体和胎儿隔室之间达到平衡。在灌注实验期间,所研究的化合物均未影响胎盘的代谢、功能和组织病理学参数。Transwell模型的数据表明缬草烯酸不会穿过胎盘细胞层。综合来看,我们的数据表明在整个孕期,胎儿接触金丝桃苷和金丝桃素的可能性极小,但接触缬草烯酸的可能性不大。