Functional Metabolomics Analysis Elucidating the Metabolic Biomarker and Key Pathway Change Associated With the Chronic Glomerulonephritis and Revealing Action Mechanism of Rhein
Wei Yu, Wei Yang, Mingyan Zhao, Xianglin Meng
Abstract
Chronic glomerulonephritis (CGN) as the culprit of kidney failure can increase the mortality of critically ill patients and seriously threatens people's health all over the world. This study using metabolomics strategy is to reveal the potential therapeutic mechanism-related targets to evaluate the effects of rhein (RH) on CGN rats. Changes of serum metabolites and pathways were analyzed by non-targeted metabolomic method based on liquid chromatography-mass spectrometry (LC-MS) combined with ingenuity pathway analysis. In addition, the levels of biochemical indicators were also detected. A total of twenty-five potential biomarkers were identified to express serum metabolic turbulence in CGN animal model, and then sixteen biomarkers were regulated by RH trending to the normal states. From metabolite enrichment and pathway analysis, pharmacological activity of RH on CGN were mainly involved in six vital metabolic pathways including phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism, arachidonic acid metabolism, TCA cycle, alanine, aspartate and glutamate metabolism, arginine and proline metabolism. It suggested CGN treatment with RH, which may be mediated via interference with metabolic pathway such as amino acid metabolism, arachidonic acid metabolism and TCA cycle to regulating inflammation, oxidation response and immune regulation against CGN. It showed that metabolomics method offer deeply insight into the therapeutic mechanisms of natural product.