High-throughput system metabolomics method reveals new mechanistic insights of chlorogenic acid by using liquid chromatography coupled to high resolution mass spectrometry

摘要

It has increasingly been recognized that metabolism is highly interconnected with disease, and system metabolomics studies have aimed to discover metabolic biomarkers and analyze the pathways of metabolome phenotypes. To better understand the metabolic alteration related with disease, a urine metabolic profile using a high-throughput system metabolomics technology approach was applied to probe the underlying molecular mechanisms of alcohol-induced liver injury and the therapeutic effects of chlorogenic acid (CA). In this study, endogenous low-molecular-weight metabolites were characterized using liquid chromatography coupled with mass spectrometry (LC-MS). The acquired data was parsed by principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) to identify potential biomarkers. A total of 19 biomarkers were identified in a model of alcohol-induced liver injury rats, and it was found that chlorogenic acid had a regulatory effect on 14 of them, associated with multiple metabolic pathways. Comprehensive pathway analysis suggests that CA has the ability to regulate abnormal metabolic states. In addition, accessory examinations such as biochemical analysis and histopathological observations were also performed that showed similar results. As a natural product agent against ethanol-induced liver injury, CA was validated in the rebalancing of a wide range of metabolic disorders. High-throughput system metabolomics represents a powerful approach for revealing new mechanistic insights of natural products.