Ginkgolide B alleviates placental inflammation and ferroptosis in gestational diabetes through inhibition of the NLRP3 inflammasome and activation of Nrf2/HO-1 signaling.

INTRODUCTION: Gestational diabetes mellitus (GDM) occurs in pregnant women of advanced maternal age and is characterized by dysregulated elevation of blood glucose levels. Ginkgolide B (GB) is extracted from Ginkgo biloba leaves and possesses anti-inflammatory as well as antioxidant effects. This study aimed to assess the function of GB in gestational diabetes mellitus (GDM) and explore the underlying mechanisms. METHODS: Pregnant C57BL/KsJ-db/+ mice were assigned to the untreated GDM group or treated orally with GB at 100 or 200 mg/kg. Glucose tolerance, insulin sensitivity, fasting blood glucose, plasma insulin levels, and pregnancy outcomes were evaluated. Placental inflammation, oxidative stress, ferroptosis-related proteins, NLRP3 inflammasome components, and proteins involved in the Nrf2/HO-1 signaling pathway were assessed using ELISA, histological staining, immunofluorescence, biochemical assays, and Western blotting. RESULTS: Compared with the Control mice, GDM mice exhibited impaired glucose tolerance and insulin sensitivity, elevated fasting blood glucose and plasma insulin levels, increased placental inflammation and oxidative stress, enhanced ferroptosis, and reduced litter size. GB treatment significantly improved these metabolic and pregnancy-related abnormalities, attenuated inflammatory cytokine production and placental injury, reduced reactive oxygen species accumulation and lipid peroxidation, and restored GPX4 and SLC7A11 expressions. In addition, GB inhibited NLRP3 inflammasome activation, while restoring the expression of Nrf2, HO-1, and NQO1 in placental tissues. DISCUSSION: This study showed the beneficial effects of GB in GDM, suggesting potential therapeutic approaches for preventing the progression of GDM management.