Isorhynchophylline Inhibits NLRP3 Inflammasome and Improves Gestational Diabetes.

Abstract

This study aims to investigate the effects and underlying mechanisms of isorhynchophylline (IRN) on gestational diabetes mellitus (GDM). The db/+ mice were randomly divided into four groups: GDM, GDM + IRN (20 mg/kg), and GDM + IRN (40 mg/kg). Blood glucose and insulin tolerance were assessed using intraperitoneal glucose tolerance tests (IPGTTs) and intraperitoneal insulin tolerance tests (IPITTs) on gestational day 10. On gestational day 20, placental inflammation (tumor necrosis factor [TNF]-α, interleukin [IL]-6, IL-1β), oxidative stress markers (malondialdehyde [MDA], SOD, glutathione peroxidase [GPx], and glutathione [GSH]), and nuclear factor-κB/NOD-like receptor protein 3 [NLRP3] inflammasome activity were measured using enzyme-linked immunosorbent assay (ELISA), immunoblotting, and biochemical assays. IRN significantly improved blood glucose levels and insulin tolerance in GDM mice. IRN treatment reduced placental inflammation. In addition, oxidative stress in the placenta was alleviated in the IRN-treated groups, leading to improved placental function and healthier fetal development. The birth weight of offspring was higher in the IRN-treated groups compared with untreated GDM mice. Furthermore, IRN inhibited the activation of the NLRP3 pathway. IRN significantly improves metabolic and inflammatory parameters in GDM through the NF-κB/NLRP3 pathway, highlighting its potential therapeutic benefits for managing GDM and improving maternal and fetal outcomes.