Combined Effects of Methyldopa and Flavonoids on the Expression of Selected Factors Related to Inflammatory Processes and Vascular Diseases in Human Placenta Cells—An In Vitro Study

Abstract

The aim of the study was to investigate combined effects of flavonoids (apigenin, baicalein, chrysin, quercetin, and scutellarin) and methyldopa on the expression of selected proinflammatory and vascular factors in vitro for prediction of their action in pregnancy-induced hypertension. The research was conducted on a trophoblast-derived human choriocarcinoma cell line and a primary human umbilical vein endothelial cell line. Cytotoxicity of compounds in selected concentrations (20, 40, and 100 µmol) was measured using the MTT test and the concentration of 40 µmol was selected for further analysis. Subsequently, their effects with methyldopa on the expression of selected markers responsible for inflammation (TNF-α; IL-1β; IL-6) and vascular effects (hypoxia-inducible factor 1α—HIF-1α; placental growth factor—PIGF; transforming growth factor β—TGF-β; vascular endothelial growth factor—VEGF) at the mRNA and protein levels were assessed. It was found that every combined administration of a flavonoid and methyldopa in these cells induced a down-regulating effect on all tested factors, except PIGF, especially at the mRNA expression level. As hypertension generally raises TNF-α, IL-1β, IL-6, HIF-1α, TGF-β, and VEGF mRNA expression and/or protein levels, the results obtained in the studied model may provide a positive prognostic factor for such activity in vivo.