Abou-El-Naga Amoura M, Mansour Hend Abd El-Halim, El-Sawi Mamdouh R, El-Dein Mai Alaa, Tag Yasmin M, Ghanem Reham A, Shawki Manar A
Zoology Department, Faculty of Science, Mansoura University, Mansoura, Egypt.
Zoology and Entomology Department, Faculty of Science, Al-Azhar University, Cairo, Egypt.
PLoS One. 2025 Apr 4;20(4):e0321022. doi: 10.1371/journal.pone.0321022. eCollection 2025.
Maternal diabetes mellitus is linked to neurobiological and cognitive impairments, increasing the risk of brain and cerebellar defects in diabetic pregnant rats and their offspring. Momordica charantia (bitter melon) possesses antidiabetic properties due to its bioactive compounds, including phenolics, alkaloids, proteins, steroids, inorganic compounds, and lipids. Forty pregnant rats were randomly assigned to four groups: control; M charantia (BM); diabetic (DM); and diabetic treated with M charantia (BM+DM). Diabetic maternal rats showed significantly elevated serum glucose, insulin, leptin, and homeostasis model assessment of insulin resistance (HOMA-IR) levels, with a concomitant decrease in insulin sensitivity check index (QUICKI), glucose transporter 4 (GLUT4), adenosine monophosphate-activated protein kinase (AMPK), acetylcholine (ACh), and dopamine. Oxidative stress markers in cerebellar tissue indicated increased malondialdehyde (MDA) and decreased glutathione (GSH) levels. Cerebellar tissue analysis revealed significantly reduced superoxide dismutase (SOD), catalase (CAT), B-cell lymphoma 2 (Bcl-2), and nerve growth factor (NGF), while Bcl-2-associated X protein (BAX) and glial fibrillary acidic protein (GFAP) were elevated. Histological and ultrastructural analysis of the diabetic maternal cerebellum showed moderate vacuolation of the neuropil in all cerebellar cortical layers, along with Purkinje cell degeneration and necrosis, including Nissl substance loss. Offspring of diabetic mothers exhibited multifocal Purkinje cell loss, empty baskets, and cerebellar cortical dysplasia with abnormal tissue development and organization. In conclusion, M. charantia supports central nervous system health in diabetic pregnant rats and their offspring by enhancing antioxidant markers, regulating GFAP and NGF, and mitigating apoptosis, ultimately improving cerebellar pathology and neural development.
妊娠糖尿病与神经生物学和认知障碍有关，增加了糖尿病孕鼠及其后代出现脑和小脑缺陷的风险。苦瓜因其生物活性化合物（包括酚类、生物碱、蛋白质、类固醇、无机化合物和脂质）而具有抗糖尿病特性。40只孕鼠被随机分为四组：对照组；苦瓜组（BM）；糖尿病组（DM）；以及苦瓜治疗的糖尿病组（BM+DM）。糖尿病母鼠的血清葡萄糖、胰岛素、瘦素和胰岛素抵抗稳态模型评估（HOMA-IR）水平显著升高，同时胰岛素敏感性检查指数（QUICKI）、葡萄糖转运蛋白4（GLUT4）、腺苷单磷酸激活蛋白激酶（AMPK）、乙酰胆碱（ACh）和多巴胺降低。小脑组织中的氧化应激标志物表明丙二醛（MDA）增加，谷胱甘肽（GSH）水平降低。小脑组织分析显示超氧化物歧化酶（SOD）、过氧化氢酶（CAT）、B细胞淋巴瘤2（Bcl-2）和神经生长因子（NGF）显著减少，而Bcl-2相关X蛋白（BAX）和胶质纤维酸性蛋白（GFAP）升高。糖尿病母鼠小脑的组织学和超微结构分析显示，所有小脑皮质层的神经毡均有中度空泡化，同时伴有浦肯野细胞变性和坏死，包括尼氏体丧失。糖尿病母亲的后代表现出多灶性浦肯野细胞丢失、空篮和小脑皮质发育异常，组织发育和结构异常。总之，苦瓜通过增强抗氧化标志物、调节GFAP和NGF以及减轻细胞凋亡，支持糖尿病孕鼠及其后代的中枢神经系统健康，最终改善小脑病理和神经发育。
