Abstract
Diabetes causes a variety of end-stage organ complications, including diabetic nephropathy. Metabolomics offers an approach for characterizing biofluid metabolic changes, but studies focusing on diabetic nephropathy are limited due to the loss of tissue-specific metabolic information. A microdialysis application for the sampling of intact endogenous metabolites has been developed, utilizing two probes simultaneously inserted into the kidney tissues and jugular vein of rats with type 2 diabetes. The comprehensive and quantitative analysis of 20 diagnostic biomarkers closely realated to type 2 diabetes and its complications were performed. Results indicated that amino acid and nucleotide levels were lower in diabetic rats, revealing that the metabolic pathways of amino acid, as well as purine and pyrimidine, were disturbed. Targeted metabolomics using mass spectrometry was performed to find potential therapeutic biomarkers and related metabolic pathways of Gardenia jasminoides (G. jasminoides) for treating diabetes. Results suggested that seven biomarkers in the kidney and five biomarkers in the blood were related to G. jasminoides. In addition, the marked perturbations of pathways were regulated after treatment with G. jasminoides, including amino acid metabolism and purine metabolism. These biomarkers and metabolic pathways provided new understanding for molecular mechanisms of G. jasminoides for treating diabetes and its complications.
Highlights
Metabolomics strategies can be divided into untargeted and targeted approaches
Tryptophan is an essential amino acid that can be metabolized through methoxyindole and kynurenine pathways
The majority of tryptophan is metabolized by the kynurenine pathway (KP)[24], leading to the production of various metabolites, including kynurenate and xanthurenate
Summary
Metabolomics strategies can be divided into untargeted and targeted approaches. The emergence of targeted metabolome profiling is an important development in metabolomics. Epalrestat is a noncompetitive and reversible ARI It reduces the accumulation of intracellular sorbitol which is believed to be the cause of diabetic neuropathy, retinopathy and nephropathy[13]. A series of metabolites like some amino acids[15, 16], such as purine, pyrimidine[19], and sorbital[20], were identified as diagnostic biomarkers of T2D These pivotal metabolites were selected as targeted metabolites in our research. Metabolomics is a powerful approach to explore the multi-target therapeutic mechanism underlying the influence of TCMs. The aim of targeted metabolomics analysis is to determine tissue-specific metabolic profiles and metabolic alterations in response to G. jasminoides treatment. We performed simultaneously qualitative and quantitative analyses of multiple metabolites in the blood and kidney tissues and investigated the mechanism of G. jasminoides for treating diabetes and its complications
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