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虾青素:一种海洋药物,通过抑制基质金属蛋白酶-13,改善斑马鱼模型中与脑血管损伤相关的阿尔茨海默病。

Astaxanthin: A Marine Drug That Ameliorates Cerebrovascular-Damage-Associated Alzheimer's Disease in a Zebrafish Model via the Inhibition of Matrix Metalloprotease-13.

机构信息

Department of Pharmacognosy, JSS College of Pharmacy, Mysore 643001, Karnataka, India.

Pharmacology Unit, Faculty of Pharmacy, AIMST University, Semeling, Bedong 08100, Kedah, Malaysia.

出版信息

Mar Drugs. 2023 Jul 31;21(8):433. doi: 10.3390/md21080433.

Abstract

Alzheimer's disease (AD) is a major type of dementia disorder. Common cognitive changes occur as a result of cerebrovascular damage (CVD) via the disruption of matrix metalloproteinase-13 (MMP-13). In diabetic cases, the progress of vascular dementia is faster and the AD rate is higher. Patients with type 2 diabetes are known to have a higher risk of the factor for AD progression. Hence, this study is designed to investigate the role of astaxanthin (AST) in CVD-associated AD in zebrafish via the inhibition of MMP-13 activity. CVD was developed through the intraperitoneal and intracerebral injection of streptozotocin (STZ). The AST (10 and 20 mg/L), donepezil (1 mg/L), and MMP-13 inhibitor (i.e., CL-82198; 10 μM) were exposed for 21 consecutive days in CVD animals. The cognitive changes in zebrafish were evaluated through light and dark chamber tests, a color recognition test, and a T-maze test. The biomarkers of AD pathology were assessed via the estimation of the cerebral extravasation of Evans blue, tissue nitrite, amyloid beta-peptide aggregation, MMP-13 activity, and acetylcholinesterase activity. The results revealed that exposure to AST leads to ameliorative behavioral and biochemical changes. Hence, AST can be used for the management of AD due to its multi-targeted actions, including MMP-13 inhibition.

摘要

阿尔茨海默病(AD)是一种主要的痴呆症。常见的认知变化是由于脑血管损伤(CVD)通过基质金属蛋白酶-13(MMP-13)的破坏而发生的。在糖尿病病例中,血管性痴呆的进展更快,AD 发病率更高。已知 2 型糖尿病患者患 AD 进展因素的风险更高。因此,本研究旨在通过抑制 MMP-13 活性,研究虾青素(AST)在斑马鱼 CVD 相关 AD 中的作用。通过腹腔内和脑内注射链脲佐菌素(STZ)来发展 CVD。AST(10 和 20mg/L)、多奈哌齐(1mg/L)和 MMP-13 抑制剂(即 CL-82198;10μM)在 CVD 动物中连续 21 天暴露。通过在明暗箱测试、颜色识别测试和 T 迷宫测试中评估斑马鱼的认知变化。通过估计 Evans 蓝脑外渗、组织亚硝酸盐、淀粉样β肽聚集、MMP-13 活性和乙酰胆碱酯酶活性来评估 AD 病理学的生物标志物。结果表明,AST 的暴露导致行为和生化变化的改善。因此,AST 可因其多靶点作用,包括 MMP-13 抑制作用,用于 AD 的治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10ad/10455645/6f25ee105212/marinedrugs-21-00433-g001.jpg

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