Improvement Effect and Its Mechanism of Marmesin on Cognitive Impairment in Mice with Alzheimer's Disease
10.13359/j.cnki.gzxbtcm.2024.10.035
- VernacularTitle:异紫花前胡内酯对阿尔茨海默病小鼠认知障碍的改善作用及机制研究
- Author:
Zhuang-Zhuang LIU
1
;
Shi-Jie SU
;
Hong-Ying YANG
;
Hai-Xia DING
;
Ya-Ru PAN
;
Han CAI
;
Lei-Jie LIN
;
Wei-Rong LI
;
Qi WANG
Author Information
1. 广州中医药大学科技创新中心,广东广州 510405
- Keywords:
marmesin;
Alzheimer's disease;
cognitive impairment;
network pharmacology;
NRF2/SIRT3 pathway;
oxidative stress;
neuroinflammation;
mice
- From:
Journal of Guangzhou University of Traditional Chinese Medicine
2024;41(10):2758-2768
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the improvement effect and mechanism of marmesin on cognitive impairment in Alzheimer's disease(AD)mice.Methods Fifty mice were randomly divided into five groups:blank group,model group,low-and high-dose marmesin groups and donepezil(positive drug)group,with 10 mice in each group.After 21 days of continuous administration,except for the blank group,the mice in other groups were given intraperitoneal injection of scopolamine to establish the AD model.Network pharmacology was used to construct the protein-protein interaction(PPI)network of common targets of marmesin in the treatment of AD,and gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis were performed to provide further research direction.The cognitive function of AD model mice was evaluated by Morris water maze,open field test and new object recognition test.Nissl staining was used to observe the damage of hippocampal neurons.The levels of acetylcholine(Ach),acetylcholine transferase(ChAT),acetylcholinesterase(AChE),reactive oxygen species(ROS),malondialdehyde(MDA)and catalase(CAT)in hippocampus of mice were detected by kit.The protein expression levels of interleukin 6(IL-6),interleukin 1β(IL-1 β),tumor necrosis factor α(TNF-α),nuclear factor E2-related factor 2(NRF2),silent information regulator homologous protein 3(SIRT3),Kelch-like ECH-associated protein 1(KEAP1),quinone oxidoreductase 1(NQO1)and heme oxygenase 1(HO-1)in hippocampus were detected by Western Blot.Results Compared with the model group,the latency of Morris water maze test was significantly shortened in the high-dose marmesin group,the time of entering the target area in the open field new object test and the movement distance in the central area of the open field were prolonged,the number of neurons in the hippocampal CA1 and CA3 regions was significantly increased,the levels of ChAT and Ach in the hippocampus were significantly increased,AChE level was significantly decreased,CAT level was significantly increased,ROS and MDA levels were significantly decreased,TNF-α expression level was decreased,SIRT3 and HO-1 expression levels were increased,and KE AP1 protein expression level was decreased,the differences being statistically significant(P＜0.05 or P＜0.01 or P＜0.001).Conclusion Marmesin can effectively improve the learning and memory impairment of AD mice,and its mechanism may be related to the activation of NRF2/SIRT3 signaling pathway,thereby alleviating oxidative stress level and neuroinflammation,and repairing cholinergic neuron function.
