Abstract

Icariin mitigated high glucose-induced injury in HTR-8/SVneo cells • Icariin activated mitophagy and attenuated mitochondrial damage in HG-treated HTR-8/SVneo Cells • Icariin activated mitophagy by regulating the S100A9/RAGE pathway Objective Gestational diabetes mellitus (GDM) is a common metabolic complication during pregnancy, which can readily lead to adverse pregnancy outcomes. Studies have shown that icariin (ICA) possesses anti-inflammatory and anti-oxidative stress properties and can mitigate high glucose-induced cellular damage. This study aims to investigate the effects and underlying mechanisms of ICA on a GDM cell model. Methods An in vitro GDM model was established by exposing HTR-8/Svneo cells to high glucose (HG) medium. Cell viability was measured using the CCK-8 assay. Cytotoxicity was assessed with the lactate dehydrogenase (LDH) assay kit. Flow cytometry was employed to evaluate apoptosis, mitophagy flux, and intracellular mitochondrial reactive oxygen species (ROS) levels. Western blotting and JC-1 staining were used to assess mitophagy and mitochondrial membrane potential, respectively. Results ICA alleviated the inhibitory effect of HG on the proliferation of HTR-8/SVneo cells and reduced high glucose-induced intracellular LDH level and apoptosis. Furthermore, ICA promoted mitophagy flux, decreased mitochondrial ROS levels, and attenuated mitochondrial damage in HG-treated HTR-8/SVneo cells. Mechanistically, ICA protected HTR-8/SVneo cells from HG-induced injury by targeting the S100A9/RAGE pathway. Conclusions ICA ameliorates high glucose-induced trophoblast injury by modulating the S100A9/RAGE pathway, offering a potential therapeutic strategy for the treatment of GDM.