Imagine our bodies as intricate machines that need the right fuel and energy to function properly. Just like a car needs gasoline to run, our brains need a steady supply of energy to support cognition. In the case of Alzheimer’s disease (AD), energy metabolism is thrown off balance, causing cognitive deficits. But fear not! Scientists have discovered a promising solution called Dihuang-Yinzi (DHYZ), a traditional Chinese herbal prescription. Through a combination of metabolomics analysis and network pharmacology, researchers unraveled the metabolic mechanism behind DHYZ’s therapeutic effects. They found that DHYZ targets key energy-related metabolic pathways in the brain, including glycerophospholipid metabolism and glycolysis, to combat AD. By doing so, DHYZ promotes oxidative phosphorylation and improves energy metabolism. It also decreases mitochondrial dysfunction and excessive production of reactive oxygen species (ROS), both of which contribute to AD progression. This groundbreaking study identified specific molecular targets and differential metabolites that DHYZ acts upon. It sheds light on the comprehensive benefits of DHYZ in treating AD and offers potential clues for future drug development. To delve deeper into this research, check out the full article!

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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