Pu Li, Chen Li, Yu Kun, Zhang Yueming, Wang Caifeng, Jiang Feizhou, Shi Jia, Meng Jingjing
Department of Gynecology and Obstetrics, The Fourth Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215000, China.
Arch Immunol Ther Exp (Warsz). 2025 Mar 14;73(1). doi: 10.2478/aite-2025-0006. eCollection 2025 Jan 1.
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.
本研究旨在探讨异钩藤碱（IRN）对妊娠期糖尿病（GDM）的影响及其潜在机制。将db/+小鼠随机分为四组：GDM组、GDM + IRN（20 mg/kg）组和GDM + IRN（40 mg/kg）组。在妊娠第10天，通过腹腔葡萄糖耐量试验（IPGTTs）和腹腔胰岛素耐量试验（IPITTs）评估血糖和胰岛素耐受性。在妊娠第20天，使用酶联免疫吸附测定（ELISA）、免疫印迹和生化测定法测量胎盘炎症（肿瘤坏死因子[TNF]-α、白细胞介素[IL]-6、IL-1β）、氧化应激标志物（丙二醛[MDA]、超氧化物歧化酶[SOD]、谷胱甘肽过氧化物酶[GPx]和谷胱甘肽[GSH]）以及核因子-κB/核苷酸结合寡聚化结构域样受体蛋白3[NLRP3]炎性小体活性。IRN显著改善了GDM小鼠的血糖水平和胰岛素耐受性。IRN治疗减轻了胎盘炎症。此外，IRN治疗组的胎盘氧化应激得到缓解，从而改善了胎盘功能和胎儿的健康发育。与未治疗的GDM小鼠相比，IRN治疗组后代的出生体重更高。此外，IRN抑制了NLRP3途径的激活。IRN通过NF-κB/NLRP3途径显著改善了GDM的代谢和炎症参数，突出了其在管理GDM以及改善母婴结局方面的潜在治疗益处。
