Physicochemical characterization of Q-LNP.

Diabetes mellitus (DM) is a severe metabolic disease that can have significant consequences for cognitive health. Bioflavonoids such as Trifolium alexandrinum (TA), quercetin (Q), and Biochanin-A (BCA) are known to exert a wide range of pharmacological functions including antihyperglycemic activity. This study aimed to investigate the neurotherapeutic effects of quercetin-loaded nanoparticles (Q-LNP) and BCA extracted from TA against diabetes-induced cerebral cortical damage through modulation of PI3K/Akt/GSK-3β and AMPK signaling pathways. Adult male Wistar albino rats (N = 25) were randomly assigned to one of five groups: control, diabetics fed a high-fat diet (HFD) for 2 weeks and intraperitoneally (i.p.) injected with STZ (40 mg/kg), and diabetics treated with Q-LNP (50 mg/kg BW/day), BCA (10 mg/kg BW/day), or TA extract (200 mg/kg BW/day). Treatments were applied by oral gavage once daily for 35 days. Diabetic rats treated with Q-LNP, BCA, and TA extract showed improvement in cognitive performance, cortical oxidative metabolism, antioxidant parameters, and levels of glucose, insulin, triglyceride, and total cholesterol. In addition, these treatments improved neurochemical levels, including acetylcholine, dopamine, and serotonin levels as well acetylcholinesterase and monoamine oxidase activities. Furthermore, these treatments lowered proinflammatory cytokine production for TNF-α and NF-κB; downregulated the levels of IL-1β, iNOS, APP, and PPAR-γ; and attenuated the expressions of PSEN2, BACE, IR, PI3K, FOXO 1, AKT, AMPK, GSK-3β, and GFAP. The histopathological examinations of the cerebral cortical tissues confirmed the biochemical results. Overall, the present findings suggest the potential therapeutic effects of TA bioflavonoids in modulating diabetes-induced cerebral cortical damage.

糖尿病（Diabetes mellitus, DM）是一种严重的代谢性疾病，可对认知健康造成显著不良影响。生物类黄酮（Bioflavonoids）涵盖亚历山大车轴草（Trifolium alexandrinum, TA）、槲皮素（quercetin, Q）及鹰嘴豆芽素A（Biochanin-A, BCA）等成分，已知其具备多种药理学功能，其中包括抗高血糖活性。本研究旨在探讨载槲皮素纳米粒（quercetin-loaded nanoparticles, Q-LNP）与从TA中提取的BCA，通过调控PI3K/Akt/GSK-3β及AMPK信号通路，对抗糖尿病诱导的大脑皮层损伤的神经治疗效果。本研究将25只成年雄性白化Wistar大鼠随机分为5组：正常对照组、高脂饮食（high-fat diet, HFD）喂养2周并腹腔注射（intraperitoneally, i.p.）链脲佐菌素（STZ，40 mg/kg）的糖尿病模型组、Q-LNP给药组（50 mg/kg体重/日）、BCA给药组（10 mg/kg体重/日）以及TA提取物给药组（200 mg/kg体重/日）。所有给药方式均为每日单次灌胃，持续35天。经Q-LNP、BCA及TA提取物治疗的糖尿病大鼠，其认知能力、皮层氧化代谢、抗氧化参数以及血糖、胰岛素、甘油三酯、总胆固醇水平均得到改善。此外，此类治疗还可改善神经化学指标，包括乙酰胆碱、多巴胺、5-羟色胺水平，以及乙酰胆碱酯酶与单胺氧化酶活性。进一步研究显示，此类治疗可降低肿瘤坏死因子-α（TNF-α）与核因子κB（NF-κB）的促炎细胞因子生成量；下调白细胞介素1β（IL-1β）、诱导型一氧化氮合酶（iNOS）、淀粉样前体蛋白（APP）及过氧化物酶体增殖物激活受体γ（PPAR-γ）的表达水平；并减弱早老素2（PSEN2）、β位淀粉样前体蛋白裂解酶（BACE）、胰岛素受体（IR）、PI3K、叉头框蛋白O1（FOXO 1）、AKT、AMPK、GSK-3β及胶质纤维酸性蛋白（GFAP）的表达。大脑皮层组织的组织病理学检查结果证实了上述生化检测结论。综合本研究全部结果，TA来源的生物类黄酮在调控糖尿病诱导的大脑皮层损伤方面具备潜在治疗价值。