结合基于超高效液相色谱-三重四极杆飞行时间质谱的血浆脂质组学和分子药理学揭示五味子醇甲抗阿尔茨海默病的机制。

Combined with UPLC-Triple-TOF/MS-based plasma lipidomics and molecular pharmacology reveals the mechanisms of schisandrin against Alzheimer's disease.

作者信息

Zhao Tian-Tian, Zhang Ying, Zhang Cheng-Qin, Chang Ya-Fei, Cui Mei-Rong, Sun Yue, Hao Wen-Qian, Yan Yu-Meng, Gu Shuo, Xie Yao, Wei Bin-Bin

机构信息

Central Laboratory, School of Pharmacy, China Medical University, No.77 Puhe Road, Shenyang, 110122, People's Republic of China.

Hubei Three Gorges Polytechnic, No.31 Stadium Road, Yichang, 443000, People's Republic of China.

出版信息

Chin Med. 2023 Feb 6;18(1):11. doi: 10.1186/s13020-023-00714-y.

DOI:10.1186/s13020-023-00714-y

PMID:36747236

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9903588/

Abstract

BACKGROUND

Alzheimer's disease (AD), a type of neurodegeneration disease, is characterized by Aβ deposition and tangles of nerve fibers. Schisandrin is one of the main components of Fructus Schisandrae Chinensis. Researches showed that schisandrin can improve the cognitive impairment and memory of AD mice, but the specific mechanism has not been fully elucidated.

PURPOSE

The purpose of this study is to investigate the possible mechanism of schisandrin in improving AD pathology.

METHODS

The Morris water maze test was executed to detect spatial learning and memory. Ultra performance liquid chromatography-Triple time of flight mass spectrometry (UPLC-Triple-TOF/MS)-based plasma lipidomics was used to study the changes of plasma lipids. Moreover, we measured the levels of protein and mRNA expression of APOE and ABCA1 in the rat brains and in BV2 microglia.

RESULTS

Our study found that schisandrin could improve learning and memory, and reduce Aβ deposition in AD rats. Furthermore, we found that schisandrin can improve plasma lipid metabolism disorders. Therefore, we hypothesized schisandrin might act via LXR and the docking results showed that schisandrin interacts with LXRβ. Further, we found schisandrin increased the protein and mRNA expression of LXR target genes APOE and ABCA1 in the brain of AD rats and in BV2 microglia.

CONCLUSION

Our study reveals the neuroprotective effect and mechanism of schisandrin improves AD pathology by activating LXR to produce APOE and ABCA1.

摘要

背景

阿尔茨海默病（AD）是一种神经退行性疾病，其特征为β淀粉样蛋白（Aβ）沉积和神经纤维缠结。五味子醇是五味子的主要成分之一。研究表明，五味子醇可改善AD小鼠的认知障碍和记忆力，但其具体机制尚未完全阐明。

目的

本研究旨在探讨五味子醇改善AD病理的可能机制。

方法

采用Morris水迷宫试验检测空间学习和记忆能力。基于超高效液相色谱-飞行时间串联质谱（UPLC-Triple-TOF/MS）的血浆脂质组学技术研究血浆脂质变化。此外，我们检测了大鼠脑和BV2小胶质细胞中载脂蛋白E（APOE）和三磷酸腺苷结合盒转运体A1（ABCA1）的蛋白和mRNA表达水平。

结果

我们的研究发现，五味子醇可改善AD大鼠的学习和记忆能力，并减少Aβ沉积。此外，我们发现五味子醇可改善血浆脂质代谢紊乱。因此，我们推测五味子醇可能通过肝X受体（LXR）发挥作用，对接结果显示五味子醇与LXRβ相互作用。进一步研究发现，五味子醇可增加AD大鼠脑和BV2小胶质细胞中LXR靶基因APOE和ABCA1的蛋白和mRNA表达。