Ginsenoside Re suppresses high glucose-induced apoptosis of placental trophoblasts through endoplasmic reticulum stress-related CHOP/GADD153.

Background: Gestational diabetes mellitus (GDM) is a metabolic disorder that arises during pregnancy and heightens the risk of placental dysplasia. Ginsenoside Re (Re) may stabilize insulin and glucagon to regulate glucose levels, which may improve diabetes-associated diseases. Purpose: This study aims to investigate the mechanism of Re in high glucose (HG)-induced apoptosis of trophoblasts through endoplasmic reticulum stress (ERS)-related protein CHOP/GADD153. Research Design: Human trophoblast cells HTR-8/SVneo were treated with HG to simulate the HG environment in vitro , while normal glucose (NG) was used as the control. Study Sample: NG (5 mM) or HG (25 mM)-cultured HTR-8/SVneo cells were treated with 10, 20 or 40 μM Re. HG-cultured cells were treated with 5 mM ERS inducer 2-Deoxy-D-glucose (2-DG) and transfected with oe- CHO. Data Collection and/or Analysis: Cell viability and apoptosis were detected by CCK-8 and flow cytometry; LDH release, superoxide dismutase (SOD), malonaldehyde (MDA) and glutathione (GSH) levels were detected using kits; the apoptosisrelated proteins and ERS-related proteins were assessed by western blot. Results: Re (10, 20 or 40 μM) had no significant effect on NG-treated HTR-8/SVneo cell viability. Re (20 or 40 μM) could enhance the viability of HG-treated trophoblasts. Re (40 μM) inhibited apoptosis of HGtreated trophoblasts, ERS and alleviated oxidative stress evidenced by suppressed phosphorylation of PERK, IRE1α, reduced protein expression of ATF6, CHOP/GADD153, and inhibited MDA accumulation, GSH and SOD loss. ERS activation or CHOP/GADD153 overexpression reversed Re's inhibition on HG-induced apoptosis of trophoblasts. Conclusions: Re repressed HG-induced placental trophoblast apoptosis by mediating ERS-related protein CHOP/GADD153.
Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.