Pharmacological Evaluation of Aescin for Neuroprotection in Intracerebroventricular Streptozotocin Model of Alzheimer's Disease in Experimental Rats.

IF 1.6 4区 医学 Q4 BIOCHEMICAL RESEARCH METHODS
Shaveta Bhardwaj, Anu Jindal, Shamsher Singh, Romanpreet Kaur, Amarjot Kaur Grewal
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引用次数: 0

Abstract

Alzheimer's disease (AD) is a neurological disorder that results in the loss of memory and cognitive functions linked to redox disbalance, neuroinflammation, neurotransmitters changes, and the accumulation of amyloid-beta (1-42) plaques in AD. In this study, rats were administered with intracerebroventricular (ICV) streptozotocin (STZ) to produce AD-like symptoms in rats. ICV-STZ bilaterally, 3 mg/kg, was infused on days 1 and 3 with the help of Hamilton syringe by fixing cannula at the target position of rat brain using coordinates -2 mm (anteriposterior), 1.6 mm Mediolateral (ML), and 1.5 mm (dorsoventral). Learning and spatial memory were checked using Morris water maze and elevated plus maze apparatus. In ICV-STZ, rats lost their spatial and learning memory, increased level of prooxidant like Lipid peroxidation (LPO), nitrite and reduced glutathione (GSH), catalase, and superoxide dismutase (SOD) level. The increased level acetylcholinesterase (AChE) catalyzed acetylcholine (ACh) concentration indicates cholinergic neuron degeneration. Furthermore, we found raised inflammatory markers and altered neurotransmitters level after ICV-STZ. Administration of aescin (10, 20, and 30 mg/kg, p.o.) dose-dependently ameliorated the behavioral alteration and inhibited inflammatory markers like tumor necrosis factor-alpha, interleukin-6 (IL-6), and IL-1β. Furthermore, aescin restored antioxidants like GSH, SOD, and catalase and reduced the nitrite and lipid peroxidation level. AChE enzyme causes degradation of ACh, and its level was declined after treatment with aescin. Aescin also restored GABA, norepinephrine, and serotonin level in the brain with prevention of raised glutamate level. Moreover, the histopathological study confirmed neuronal pathogenesis, and aescin significantly achieved neuroprotective effect via preventing neuroinflammation, balancing redox potential, and inhibiting AChE enzyme.

七叶皂苷对实验性阿尔茨海默病大鼠脑室内链脲佐菌素模型神经保护作用的药理评价。
阿尔茨海默病(AD)是一种神经系统疾病,导致记忆和认知功能丧失,与AD中氧化还原失衡、神经炎症、神经递质改变和淀粉样蛋白- β(1-42)斑块的积累有关。在本研究中,给大鼠脑室注射链脲佐菌素(STZ),使大鼠出现ad样症状。ICV-STZ以3 mg/kg双侧剂量,于第1天和第3天用Hamilton注射器在大鼠脑靶位置固定套管,坐标为-2 mm(前后侧)、1.6 mm(中外侧)和1.5 mm(背腹侧)。采用Morris水迷宫和高架+迷宫测试学习和空间记忆。ICV-STZ组大鼠空间记忆和学习记忆丧失,脂质过氧化(LPO)、亚硝酸盐、还原性谷胱甘肽(GSH)、过氧化氢酶、超氧化物歧化酶(SOD)等促氧化剂水平升高。乙酰胆碱酯酶(AChE)催化乙酰胆碱(ACh)浓度升高提示胆碱能神经元变性。此外,我们发现ICV-STZ后炎症标志物升高,神经递质水平改变。七叶皂苷(10、20和30 mg/kg, p.o)剂量依赖性改善行为改变并抑制炎症标志物如肿瘤坏死因子- α、白细胞介素-6 (IL-6)和IL-1β。此外,七叶皂苷恢复抗氧化剂如GSH、SOD和过氧化氢酶,并降低亚硝酸盐和脂质过氧化水平。乙酰胆碱酯酶引起乙酰胆碱降解,七叶皂苷处理后乙酰胆碱水平下降。七叶皂苷还能恢复大脑中GABA、去甲肾上腺素和血清素的水平,同时防止谷氨酸水平升高。此外,组织病理学研究证实了神经元的发病机制,七叶皂苷通过预防神经炎症、平衡氧化还原电位、抑制乙酰胆碱酯酶发挥了显著的神经保护作用。
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来源期刊
Assay and drug development technologies
Assay and drug development technologies 医学-生化研究方法
CiteScore
3.60
自引率
0.00%
发文量
33
审稿时长
>12 weeks
期刊介绍: ASSAY and Drug Development Technologies provides access to novel techniques and robust tools that enable critical advances in early-stage screening. This research published in the Journal leads to important therapeutics and platforms for drug discovery and development. This reputable peer-reviewed journal features original papers application-oriented technology reviews, topical issues on novel and burgeoning areas of research, and reports in methodology and technology application. ASSAY and Drug Development Technologies coverage includes: -Assay design, target development, and high-throughput technologies- Hit to Lead optimization and medicinal chemistry through preclinical candidate selection- Lab automation, sample management, bioinformatics, data mining, virtual screening, and data analysis- Approaches to assays configured for gene families, inherited, and infectious diseases- Assays and strategies for adapting model organisms to drug discovery- The use of stem cells as models of disease- Translation of phenotypic outputs to target identification- Exploration and mechanistic studies of the technical basis for assay and screening artifacts
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