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

IF 3.1 2区医学 Q2 DEVELOPMENTAL BIOLOGY

Placenta Pub Date : 2026-09-01 Epub Date: 2026-08-22 DOI:10.1016/j.placenta.2026.08.338

Yan Cao, Li Peng, Yao Chen, Wei Chen

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引用次数: 0

Abstract

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.

查看原文本刊更多论文

银杏内酯B通过抑制NLRP3炎性体和激活Nrf2/HO-1信号通路，减轻妊娠期糖尿病患者的胎盘炎症和铁下垂。

妊娠期糖尿病（GDM）发生于高龄孕妇，以血糖水平升高异常为特征。银杏内酯B （Ginkgolide B， GB）是从银杏叶中提取的具有抗炎和抗氧化作用的物质。本研究旨在评估GB在妊娠期糖尿病（GDM）中的功能并探讨其机制。方法：将妊娠C57BL/KsJ-db/+小鼠分为未治疗组或口服GB（100、200 mg/kg）。评估葡萄糖耐量、胰岛素敏感性、空腹血糖、血浆胰岛素水平和妊娠结局。采用ELISA、组织学染色、免疫荧光、生化检测和Western blotting检测胎盘炎症、氧化应激、铁中毒相关蛋白、NLRP3炎性小体成分和Nrf2/HO-1信号通路相关蛋白。结果：与对照组小鼠相比，GDM小鼠表现出糖耐量和胰岛素敏感性受损，空腹血糖和血浆胰岛素水平升高，胎盘炎症和氧化应激增加，铁下沉加剧，产仔减少。GB处理显著改善了这些代谢和妊娠相关异常，减轻了炎症细胞因子的产生和胎盘损伤，减少了活性氧积累和脂质过氧化，恢复了GPX4和SLC7A11的表达。此外，GB抑制NLRP3炎性体的激活，同时恢复胎盘组织中Nrf2、HO-1和NQO1的表达。讨论：本研究显示了GB在GDM中的有益作用，提示了预防GDM管理进展的潜在治疗方法。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Placenta 医学-发育生物学

CiteScore

6.30

自引率

10.50%

发文量

391

审稿时长

78 days

期刊介绍： Placenta publishes high-quality original articles and invited topical reviews on all aspects of human and animal placentation, and the interactions between the mother, the placenta and fetal development. Topics covered include evolution, development, genetics and epigenetics, stem cells, metabolism, transport, immunology, pathology, pharmacology, cell and molecular biology, and developmental programming. The Editors welcome studies on implantation and the endometrium, comparative placentation, the uterine and umbilical circulations, the relationship between fetal and placental development, clinical aspects of altered placental development or function, the placental membranes, the influence of paternal factors on placental development or function, and the assessment of biomarkers of placental disorders.