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达格列净/橙皮苷组合减轻大鼠脂多糖诱导的阿尔茨海默病

Dapagliflozin/Hesperidin Combination Mitigates Lipopolysaccharide-Induced Alzheimer's Disease in Rats.

作者信息

Abd Elmaaboud Maaly A, Estfanous Remon S, Atef Aliaa, Kabel Ahmed M, Alnemari Khalid A, Naguib Tamer M, Alsufyani Shuruq E, Darwish Hany W, Arab Hany H

机构信息

Department of Pharmacology, Faculty of Medicine, Tanta University, Tanta 31527, Egypt.

Anatomy and Embryology Department, Faculty of Medicine, Tanta University, Tanta 31527, Egypt.

出版信息

Pharmaceuticals (Basel). 2023 Sep 27;16(10):1370. doi: 10.3390/ph16101370.

DOI:10.3390/ph16101370
PMID:37895841
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10609711/
Abstract

Alzheimer's disease (AD) is the most common form of neurodegenerative disorders worldwide. Its pathologic features include massive neuroinflammation with abnormal deposition of β-amyloid peptide in the cerebral tissues leading to degeneration of the brain neurons. Adverse effects associated with the traditional drugs used for the treatment of this pathological condition have directed the research efforts towards searching for alternative effective agents with minimal adverse effects. The aim of this study was to elucidate the potential ameliorative effects of dapagliflozin and/or hesperidin on Alzheimer's disease (AD) induced by lipopolysaccharide (LPS) injection in rats. In a rodent model of AD, the effect of dapagliflozin with or without hesperidin on the biochemical parameters and the behavioral tests as well as the histopathological parameters was determined. Each of dapagliflozin and hesperidin restored the behavioral tests to the reference values, augmented the antioxidant defense mechanisms, ameliorated the neuronal inflammatory responses, combatted the changes in Toll-like receptor-4 (TLR-4)/High-mobility group box 1 (HMGB1) protein signaling and receptors of advanced glycation end products (RAGE) levels, and restored the balance between the apoptotic signals and autophagy in the hippocampal tissues. Additionally, both agents exhibited an outstanding ability to combat LPS-induced perturbations in the histopathological and electron microscopic image of the brain tissues. These favorable effects were significantly encountered in the group treated with dapagliflozin/hesperidin combination when compared versus animals treated with either dapagliflozin or hesperidin. In conclusion, inhibition of the hippocampal HMGB1/TLR4/RAGE signaling, the pro-inflammatory axis, and apoptosis alongside augmentation of the antioxidant defenses and autophagy can be regarded as beneficial effects by which dapagliflozin/hesperidin combination may combat LPS-triggered AD.

摘要

阿尔茨海默病（AD）是全球最常见的神经退行性疾病形式。其病理特征包括大量神经炎症，伴有β-淀粉样肽在脑组织中异常沉积，导致脑神经元退化。用于治疗这种病理状况的传统药物的不良反应促使研究工作转向寻找不良反应最小的替代有效药物。本研究的目的是阐明达格列净和/或橙皮苷对脂多糖（LPS）注射诱导的大鼠阿尔茨海默病（AD）的潜在改善作用。在AD的啮齿动物模型中，测定了达格列净联合或不联合橙皮苷对生化参数、行为测试以及组织病理学参数的影响。达格列净和橙皮苷均可将行为测试恢复到参考值，增强抗氧化防御机制，改善神经元炎症反应，对抗Toll样受体4（TLR-4）/高迁移率族蛋白B1（HMGB1）蛋白信号传导变化以及晚期糖基化终产物受体（RAGE）水平，并恢复海马组织中凋亡信号与自噬之间的平衡。此外，两种药物在对抗LPS诱导的脑组织病理组织学和电子显微镜图像扰动方面均表现出卓越能力。与单独使用达格列净或橙皮苷治疗的动物相比，达格列净/橙皮苷联合治疗组显著出现了这些有益效果。总之，抑制海马体HMGB1/TLR4/RAGE信号传导、促炎轴和细胞凋亡，同时增强抗氧化防御和自噬，可被视为达格列净/橙皮苷联合用药对抗LPS引发的AD的有益作用。

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