Advanced in vitro safety assessment of herbal medicines for the treatment of non-psychotic mental disorders in pregnancy

ABSTRACT: When confronted with non-psychotic mental disorders, pregnant women often refrain from using synthetic drugs. Instead, they resort to well-known herbal medicines (phytopharmaceuticals) such as St. John's wort, California poppy, valerian, lavender, and hops, which have proven sedative, anxiolytic, or antidepressant properties. Nevertheless, these herbal medicines are not officially approved in pregnancy due to lack of safety data. Using a variety of in vitro methods (determination of cytotoxicity, apoptosis induction, genotoxicity, effects on metabolic properties, inhibition/induction of differentiation) in a commonly used placental cell line (BeWo b30), we could previously show that extracts from these plants are likely to be safe at usual clinical doses. In the present work, we wanted to deepen our safety assessment of these herbal medicines by (i) looking for possible effects on gene expression and (ii) using the same in vitro methods to characterize effects of selected phytochemicals that might conceivably cause safety issues. Proteomics results were promising as none of the five extracts significantly affected the protein expression by up- or down-regulation. Protopine (contained in California poppy), valerenic acid (in valerian), and linalool (in lavender) were inconspicuous in all experiments and showed no adverse effects. Hyperforin and hypericin (two constituents from St. John's wort) and valtrate (typical for valerian) were the most discernible phytochemicals with respect to the selected safety parameters (cytotoxic and apoptotic effects). A decrease in BeWo b30 viability was evident with hypericin (≥ 1 µM) and valtrate (≥ 10 µM), whereas hyperforin (≥ 3 µM), hypericin (30 µM) and valtrate (≥ 10 µM) induced cell apoptosis. None of the tested phytochemicals resulted in genotoxic effects at concentrations of 0.1 and 1 µM and thus are not DNA damaging. No decrease in glucose consumption or lactate production was observed under the influence of the phytochemicals, except for valtrate (at all concentrations). No compound induced or inhibited BeWo b30 cell differentiation, except for hyperforin (≥ 1 µM) that had an inhibitory effect. This study confirms previous observations suggesting that the extracts from St. John's wort, California poppy, valerian, lavender, and hops are likely to be safe during pregnancy. Attainment of high plasma concentrations of a few relevant compounds – hyperforin and hypericin from St. John's wort and valtrate from valerian – deserves though special attention. Clinical studies during pregnancy are needed to substantiate these in vitro data.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell

DISEASE(S): Gestational Choriocarcinoma

SUBMITTER: Deborah Spiess  

LAB HEAD: Ana Paula Simões-Wüst

PROVIDER: PXD031765 | Pride | 2022-06-27

REPOSITORIES: Pride