Protective effects of alpinumisoflavone against streptozotocin-induced gestational diabetes mellitus in female rats: mechanistic insights and therapeutic potential

Zhu, YanZhang, YuLiu, FeiyanXiao, Jiao

ABSTRACT Purpose: To examine the protective effect of alpinumisoflavone against streptozotocin (STZ)-induced gestational diabetes mellitus (GDM) in female rats and explored the underlying mechanisms. Methods: Female rats were used in this study, and intraperitoneal administration of STZ (55 mg/kg) was used to induce diabetes. Body weight, blood glucose level, fetuses, placental weight, and placental index were estimated. Oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) were performed. The levels of resistin, glycated hemoglobin (HbA1c), hepatic glycogen, free fatty acid (FFA), adiponectin, serum C-peptide, leptin, visfatin, intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), lipids, oxidative stress, inflammatory cytokines, and other parameters were estimated. mRNA expression was estimated in the pancreatic tissue. Results: Alpinumisoflavone treatment significantly (p < 0.001) enhanced body weight and fetuses and decreased placental weight and placental index. Alpinumisoflavone treatment significantly (p < 0.001) decreased blood glucose levels (BGL) and improved plasma insulin levels. Alpinumisoflavone treatment significantly (p < 0.001) suppressed the glucose and insulin levels in the OGTT and ITT. Alpinumisoflavone treatment significantly (p < 0.001) altered the levels of resistin, HbA1c, hepatic glycogen, FFA, Adiponectin, serum C-peptide, leptin, visfatin, ICAM-1, and VCAM-1; lipid parameters; oxidative stress parameters; inflammatory cytokines and inflammatory parameters, viz., cyclooxygenase-2 (COX-2), and nuclear kappa B factor (NF-κB). Alpinumisoflavone treatment significantly (p < 0.001) altered the mRNA expression levels of Toll-like receptor 4, nuclear kappa B factor65 (NF-κB65), NOD-, LRR-, pyrin domain-containing protein 3 (NLRP3), MyD88, SREBP-1, stearoyl-CoA desaturase-1 (SCD1), FAS, and ACC. Conclusion: Alpinumisoflavone has a protective effect against STZ-induced GDM via alteration of the TLR4/MyD88/NF-κB signaling pathway.