Hypericum caprifoliatum and Hypericum connatum affect human trophoblast-like cells differentiation and Ca(2+) influx

Objective: To study the effect of crude methanol and n-hexane extracts of Hypericum connatum (H. connatum) and Hypericum caprifoliatum on trophoblast-like cells.

Methods: BeWo and JEG-3 trophoblast-like cells were submitted to different extract concentrations (1, 5, 10 and 15 µg/mL) and evaluated in relation to cell viability and in vitro trophoblast differentiation and function. Cell viability was evaluated using WST-1 reagent. Differentiation was measured by luciferase production, hCG production/release, and mitogen-activated protein kinase signaling pathway activation. The function of the trophoblast-like cells was measured by (45)Ca(2+) influx evaluation.

Results: The results showed a decrease in cell viability/proliferation. Both plants and different extracts induced a significant decrease in hCG production/release and luciferase production. H. connatum did not cause mitogen-activated protein kinase signaling pathway disturbance; however, Hypericum caprifoliatum n-hexane extract at 15 µg/mL inhibited extracellular signal-regulated kinase 1/2 activation. The significant increase in Ca(2+) influx by JEG-3 cells was seen after short and long incubation times with H. connatum methanolic extract at 15 µg/mL.

Conclusions: The results indicated that these two Hypericum species extracts can interfere on trophoblast differentiation and Ca(2+) influx, according to their molecular diversity. Although in vivo experiments are necessary to establish their action on placental formation and function, this study suggests that attention must be paid to the potential toxic effect of these plants.