Protective Effect of Gigantol Against Streptozotocin-Induced Gestational Diabetes Mellitus via Modulation of the Nrf2/HO-1, TLR4/MyD88/NF-κB, and PI3K/Akt/GSK-3β Signaling Pathways.

Gestational diabetes mellitus (GDM) is a chronic metabolic disease occur during the pregnancy which is characterized via insulin resistance, hyperglycemia, inflammation and oxidative stress. Gigantol, a naturally occurring bibenzyl phytoconstituents showed the anti-inflammatory and antioxidant potential against various disease. The aim of the current study was to investigate the protective effect of gigantol against streptozotocin (STZ) induced GDM in female rats. Intraperitoneal administration of STZ (25 mg/kg) was used for induction the GDM in the rats and rats were received the oral administration of different doses of gigantol. The body weight, fetal weight, placental weight and placental index. The oral glucose tolerance test (OGTT), insulin tolerance test (ITT) estimated and calculate the area the under curve (AUC). Antioxidant parameters, inflammatory cytokines, inflammatory and apoptosis parameters were estimated. The mRNA expressions were also estimated. Gigantol treatment significantly improved the body weight, fetal weight and suppressed the placental weight and index. Gigantol remarkably altered the fasting blood glucose, plasma insulin, HOMA-IR and HOMA-β. Its also suppressed the blood glucose level during OGTT and ITT. Gigantol remarkably altered the level of AGE, visfatin, adiponectin, leptin, ICAM-1, VCAM-1, HO-1, Nrf2; antioxidant parameters, lipid parameters, inflammatory cytokines, inflammatory parameters and apoptosis parameters. Gigantol significantly altered the mRNA expression of Akt, MyD88, NF-κB, PI3K, TRL4, GSK-3β, Nrf2 and HO-1. Gigantol exhibited a protective effect against GDM via alterations in the Nrf2/HO-1, TLR4/MyD88/NF-κB, and PI3K/Akt/GSK-3β signaling pathways.