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.

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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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