Dihuang-Yinzi Alleviates Cognition Deficits via Targeting Energy-Related Metabolism in an Alzheimer Mouse Model as Demonstrated by Integration of Metabolomics and Network Pharmacology
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 neuro...
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Published in | Frontiers in aging neuroscience Vol. 14; p. 873929 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
Switzerland
Frontiers Research Foundation
01.04.2022
Frontiers Media S.A |
Subjects | |
Online Access | Get full text |
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Summary: | 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
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
ameliorating energy-related metabolism. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Reviewed by: Zijuan Liu, Oakland University, United States; Shijun Yan, Indiana University Bloomington, United States; Jinhai Huo, University of Florida, United States This article was submitted to Alzheimer’s Disease and Related Dementias, a section of the journal Frontiers in Aging Neuroscience These authors have contributed equally to this work Edited by: Fushun Wang, Nanjing University of Chinese Medicine, China |
ISSN: | 1663-4365 1663-4365 |
DOI: | 10.3389/fnagi.2022.873929 |