Diabetes-associated cognitive dysfunction is linked to chronic hyperglycemia, oxidative stress, inflammation, cholinergic dysfunction, and neuronal degeneration. We investigated the antidiabetic and neuroprotective activity of a mixture of Sclerocarya birrea, Nauclea latifolia, and Piper longum (SNP) in type 2 diabetic (T2D) rat model-induced memory impairment. Fructose (10%) and streptozotocin (35 mg/kg) were used to induce T2D in male Wistar rats. Diabetic animals received distilled water, metformin (200 mg/kg), or SNP mixture (75, 150, or 300 mg/kg). HPLC–MS profiling of the mixture was performed. Behavioral testing was conducted using the Y-maze, NORT, and Morris water mazes to assess learning and memory. Biochemical markers were evaluated, including carbohydrate metabolism, oxidative/nitrative stress, pro-inflammatory markers, and acetylcholinesterase activity. Histopathological examination of the pancreas and hippocampus was also performed. Fructose/STZ administration resulted in T2D, impaired short- and long-term memory, significantly increased oxidative/nitrative stress, pro-inflammatory cytokine levels, acetylcholinesterase activity (AChE), hippocampal neuronal loss and degeneration in CA1 and CA3 subfields, and neuronal vacuolation in DG. SNP mixture at 150 and 300 mg/kg significantly improved blood glucose and memory function in diabetic rats. The mixture reduced oxidative/nitrative stress and increased endogenous antioxidant levels. It also reduced serum IL-1β, INF-γ and TNF-α levels and ameliorated AChE activity. Histologically, SNP protected hippocampus neurons against T2D-induced neuronal necrosis and degeneration. We conclude that the aqueous extract of SNP mixture has antidiabetic and neuroprotective activities thanks to active metabolites identified in the plant mixture, which consequently normalized blood glucose, protected hippocampus neurons, and improved memory function in diabetic rats.

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中文翻译：

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硬核果、阔叶核桃和荜荠混合物的提取物可改善糖尿病相关的认知功能障碍

糖尿病相关的认知功能障碍与慢性高血糖、氧化应激、炎症、胆碱能功能障碍和神经元变性有关。我们研究了硬核果、阔叶木和荜茇(SNP)混合物对 2 型糖尿病 (T2D) 大鼠模型引起的记忆障碍的抗糖尿病和神经保护活性。果糖 (10%) 和链脲佐菌素 (35 mg/kg) 用于诱导雄性 Wistar 大鼠 T2D。糖尿病动物接受蒸馏水、二甲双胍（200 mg/kg）或 SNP 混合物（75、150 或 300 mg/kg）。对混合物进行了 HPLC-MS 分析。使用 Y 迷宫、NORT 和莫里斯水迷宫进行行为测试来评估学习和记忆。评估了生化标志物，包括碳水化合物代谢、氧化/硝化应激、促炎标志物和乙酰胆碱酯酶活性。还对胰腺和海马进行了组织病理学检查。果糖/STZ 给药导致 T2D、短期和长期记忆受损、氧化/硝化应激显着增加、促炎细胞因子水平、乙酰胆碱酯酶活性 (AChE)、海马神经元损失和 CA1 和 CA3 亚区变性以及神经元空泡形成在DG。150 和 300 mg/kg 的 SNP 混合物显着改善糖尿病大鼠的血糖和记忆功能。该混合物减少了氧化/硝化应激并增加了内源性抗氧化剂水平。它还降低血清 IL-1β、INF-γ 和 TNF-α 水平并改善 AChE 活性。从组织学角度来看，SNP 可以保护海马神经元免受 T2D 诱导的神经元坏死和变性的影响。我们得出的结论是，由于植物混合物中发现的活性代谢物，SNP 混合物的水提取物具有抗糖尿病和神经保护活性，从而使血糖正常化，保护海马神经元，并改善糖尿病大鼠的记忆功能。

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