Placental Passage of Humulone and Protopine in an Ex Vivo Human Perfusion System

Abstract

The placental passage of humulone and protopine was investigated with a human ex vivo placental perfusion model. The model was first validated with diazepam and citalopram, 2 compounds known to cross the placental barrier, and antipyrine as a positive control. All compounds were quantified by partially validated U(H)PLC-MS/MS bioanalytical methods. Only a small portion of humulone initially present in the maternal circuit reached the fetal circuit. The humulone concentration in the maternal circuit rapidly decreased, likely due to metabolization in the placenta. Protopine was transferred from the maternal to the fetal circuit, with a steady-state reached after 90 min. None of the study compounds affected placental viability or functionality, as glucose consumption, lactate production, beta-human chorionic gonadotropin, and leptin release remained constant. Histopathological evaluation of all placental specimens showed unremarkable, age-appropriate parenchymal maturation with no pathologic findings.

Medicinal Plants for the Treatment of Mental Diseases in Pregnancy: An In Vitro Safety Assessment

“…After 24 h incubation, cells were differentiated with 5 µM FSK for another 24 h. All experiments were performed at least 3 times independently (in triplicate). Analysis of β -hCG concentrations–a marker of placenta cell differentiation–was performed using cell culture supernatants by standard ELISA (see 36 for additional references). Transparent 96-well flat-bottom microplates were used for all analyses.…”

“…The active ingredients of herbal extracts are multi-compound mixtures, many of which may be metabolized by the intestinal microbiota upon oral administration or by the liver once they have been absorbed. An interdisciplinary project is underway to fill this gap and address some of these issues, ranging from metabolizing phytochemicals by intestinal microbiota to intestinal absorption, liver metabolism, and passage across the placental barrier 36 . We performed an in vitro assessment in BeWo cells of the safety profile of medicinal plants that are used to treat mild NMDs.…”