基于斑马鱼模型研究木蝴蝶苷A的抗阿尔茨海默病活性和作用机制

doi:10.3976/j.issn.1002-4026.2023.06.005

Abstract

Abstract:

To investigate the ameliorative effects of oroxin A on Alzheimer's disease (AD) and the underlying mechanism of action, a zebrafish AD model induced by aluminum chloride hexahydrate (AlCl₃) was used. Wild-type zebrafish AB larvae at 3 dpf(days post fertilization) were divided into different groups, including negative control group, AlCl₃ (80 μmol/L) model control group, AlCl₃ (80 μmol/L) combined with donepezil (6 μmol/L) positive control group, and AlCl₃ (80 μmol/L) combined with different concentrations (5, 10, and 20 μmol/L) of oroxin A test group. At 6 dpf, zebrafish behavior was monitored and analyzed using zebrafish light-dark locomotion test. Aβ deposition in zebrafish heads was assayed by thioflavin S staining. Acetylcholine assay kit tested acetylcholinesterase (AchE) activity. In addition, the expression of autophagy-related genes(beclin1、ulk1b、ulk2 and atg7) was tested by real-time quantitative polymerase chain reaction. Molecular docking was performed to validate the interaction between oroxin A and autophagy-related protein(beclin1、ulk1b、ulk2 and atg7). The results indicated that oroxin A significantly relieved the dyskinesia and inhibited Aβ deposition and AchE activity of zebrafish induced by AlCl₃. The expression of autophagy-related genes tended to be normal after oroxin A treatment. This study preliminarily revealed that oroxin A alleviated AlCl₃-induced AD symptoms in zebrafish, where the underlying mechanism of action is possibly associated with activated autophagy, providing a theoretical basis for the clinical application of oroxin A and its related research in treating AD.

Key words: Alzheimer's disease, aluminum chloride hexahydrate, autophagy, zebrafish, oroxin A

CLC Number:

R965

SHI Ruidie, GAO Xin, WANG Baokun, GAO Daili, JIN Meng, ZHANG Xiujun. Anti-Alzheimer's disease activity of oroxin A and its mechanism of action based on zebrafish model[J].Shandong Science, 2023, 36(6): 28-37.

Figures/Tables 6

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References 22

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基因名称	引物序列
rpl13a	上游: TCTGGAGGACTGTAAGAGGTATGC
	下游: AGACGCACAATCTTGAGAGCAG
beclin1	上游: GTTCAGGTGGTCTGCGTTTT
	下游: GCAAACAGAAGCCAGTGTCA
ulk1b	上游: AGGCCGAAAGTCTCACTTCA
	下游: AGCCATGTACATCGGAGACC
ulk2	上游: ACCTCTGATTGGCTGACAAAAT
	下游: GAGATTGCAAGAGGCTTGAGTT
atg7	上游: AGAGTCCAGTCCGATGTC
	下游: A GAAGTAACAGCCGAGACG

Anti-Alzheimer's disease activity of oroxin A and its mechanism of action based on zebrafish model

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