Baicalein suppresses high glucose-induced inflammation and apoptosis in trophoblasts by targeting the miRNA-17-5p-Mfn1/2-NF-κB pathway.

<bold>Introduction: </bold>Controlling inflammation and apoptosis in trophoblasts is critical for treating gestational diabetes mellitus (GDM). Baicalein (Bai) exhibits anti-inflammatory and miRNA-related effects; however, its roles and mechanisms in GDM remain unknown. Therefore, we explored whether Bai inhibited inflammation and apoptosis in human trophoblasts (HTR8 cells) and analyzed its mechanisms.<bold>Methods: </bold>HTR8 cells pretreated with Bai were subjected to the high-glucose (HG) stimulation before analyzing their viability, cytokine production and apoptosis, followed the expression profiles of small RNA sequencing data. The effects of miR-17-5p on the inflammation, mitochondrial fission, and apoptosis were investigated by ELISA, transmission electron microscopy and flow cytometry, respectively. Moreover, miR-17-5p, Mfn1/Mfn2 levels and mitochondrial morphology in human plasma and placental tissues from GDM-complicated and normal pregnant women were examined.<bold>Results: </bold>Bai decreased the secretion of TNF-α, IL-1β, IL-6 and apoptosis in HG-stimulated HTR8 cells, while miR-17-5p mediated the anti-inflammatory and anti-apoptotic effects of Bai. Mechanically, miR-17-5p targeted Mfn1/Mfn2 by affecting the mitochondrial fission and apoptosis via regulation of p-Drp1 (Ser 616) and p-NF-κB signaling. Moreover, overexpression of Mfn1/Mfn2 reversed miR-17-5p-elicited mitochondrial fission and inflammation in HG-stimulated HTR8 cells pretreated with Bai. Furhtermore, overexpression of Drp1 also reversed the anti-inflammatory effect of Mfn1/2 overexpression in HG-treated HTR8 cells via up-regulation of p65 phosphorylation. Finally, miR-17-5p was upregulated in human GDM plasma and placentas along with the reduced Mfn1/Mfn2.<bold>Discussion: </bold>We are the first to demonstrate that bai exerts anti-inflammatory and anti-apoptotic effects on GDM, likely by targeting the miRNA-17-5p-Mfn1/2-NF-κB pathway. [ABSTRACT FROM AUTHOR]