Dihuang-Yinzi Alleviates Cognition Deficits via Targeting Energy-Related Metabolism in an Alzheimer Mouse Model as Demonstrated by Integration of Metabolomics and Network Pharmacology

代谢组学 糖酵解 代谢途径 柠檬酸循环 代谢网络 药理学 烟酰胺腺嘌呤二核苷酸 新陈代谢 生物化学 NAD+激酶 背景(考古学) 氧化磷酸化 认知功能衰退 生物 化学 生物信息学 医学 疾病 内科学 痴呆 古生物学
作者
Guanghui Han,Weizhe Zhen,Dai Yuan,Hongni Yu,Dongyue Li,Tao Ma
出处
期刊:Frontiers in Aging Neuroscience [Frontiers Media]
卷期号:14 被引量:8
标识
DOI:10.3389/fnagi.2022.873929
摘要

Energy metabolism disturbance and the consequent reactive oxygen species (ROS) overproduction play a key and pathogenic role in the onset and progression of Alzheimer's disease (AD). Dihuang-Yinzi (DHYZ) is a traditional Chinese herbal prescription clinically applied to treat AD and other neurodegenerative diseases for a long time. However, the systematical metabolic mechanism of DHYZ against AD remains largely unclear. Here we aimed to explore the mechanism of DHYZ in the treatment of AD comprehensively in an in vivo metabolic context by performing metabolomics analysis coupled with network pharmacology study and experimental validation. The network pharmacology was applied to dig out the potential target of DHYZ against AD. The metabolomics analysis based on UPLC-HRMS was carried out to profile the urine of 2× Tg-AD mice treated with DHYZ. By integrating network pharmacology and metabolomics, we found DHYZ could ameliorate 4 key energy-related metabolic pathways, including glycerophospholipid metabolism, nicotinate/nicotinamide metabolism, glycolysis, and tricarboxylic acid cycle. Besides, we identified 5 potential anti-AD targets of DHYZ, including DAO, HIF1A, PARP1, ALDH3B2, and ACHE, and 14 key differential metabolites involved in the 4 key energy-related metabolic pathways. Furthermore, DHYZ depressed the mitochondrial dysfunction and the resultant ROS overproduction through ameliorating glycerophospholipid metabolism disturbance. Thereby DHYZ increased nicotinamide adenine dinucleotide (NAD+) content and promoted glycolysis and tricarboxylic acid (TCA) cycle, and consequently improved oxidative phosphorylation and energy metabolism. In the present study, we provided a novel, comprehensive and systematic insight into investigating the therapeutic efficacy of DHYZ against AD via ameliorating energy-related metabolism.
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