Hesperidin inhibits methylation and autophagy in LPS and high glucose-induced human villous trophoblasts

Abstract

IntroductionGestational diabetes mellitus (GDM) is the first occurrence of diabetes due to abnormal maternal sugar metabolism after pregnancy, which may lead to adverse pregnancy outcomes. Hesperidin is known to decrease in the cord blood of GDM with obesity, but its role is unknown. This study aims to explore the potential function of hesperidin in GDM with obesity to develop new therapeutic ideas. MethodsPeripheral blood and placental tissues from GDM and GDM with obesity patients were collected to isolate human villous trophoblasts and detection. Bioinformatics was used to analyze the differential methylation genes between GDM and GDM with obesity. Immunofluorescence was applied for the detection of CK7 expression. Cells vitality was detected by CCK8 and transwell. Molecular docking was applied to predict the binding of hesperidin and ATG7 protein. Inflammation and m6A levels was analyzed by ELISA. ATG7, LC3, TLR4 and P62 proteins was analyzed by Western blot. ResultsThe methylation of ATG7 gene was up-regulated in GDM with obesity compared with GDM. The m6A and autophagy proteins levels in GDM with obesity were higher than that in GDM. LPS with 2.5–25 mM glucose induced the increase of autophagy proteins, inflammation and m6A levels in human villous trophoblasts. Hesperidin formed hydrogen bonds and hydrophobic interactions with ATG7 proteins. Hesperidin (0.25 μM) inhibited the autophagy proteins and m6A level in LPS and 25 mM glucose-induced human villous trophoblasts. DiscussionGDM with obesity followed the increase of autophagy proteins and m6A levels. Hesperidin inhibited the autophagy proteins and m6A level in LPS and glucose-induced human villous trophoblasts.