Investigation of the Potential Material Basis and Mechanism of Astragali Radix Against Adriamycin-Induced Nephropathy Model Rat by 1H NMR and MS-Based Untargeted Metabolomics Analysis.

Abstract

Astragali Radix (AR) is one of the monarch drugs of Fangji Huangqi decoction and has the effects of inducing diuresis to alleviate edema, tonifying and strengthening the body. However, there is a paucity of research regarding the effective fraction and the underlying metabolic mechanism of AR on nephrotic syndrome (NS). This work aims to elucidate the potential mechanisms of AR treating NS, as well as to identify effective part and components. Firstly, body weight, kidney index, 24-h urea protein, and biochemical parameters were used to confirm the kidney injury. The most effective part of AR was determined based on the indicators above. Then, ¹H NMR, UHPLC-QTOF/MS, and GC-MS-based metabolomic approaches were used to investigate differential metabolites closely associated with the effective part against NS. A "C-T-P-D" network (a network diagram of "TCM prescription-herbs-components-targets-metabolites-pathways-disease") was constructed by intersecting the targets of differential metabolites with those of AR treating NS. The efficacy indicators determined the n-butanol part of AR as the best effective part. Multiplatform metabolomics and network pharmacology study indicated that the potential mechanism for treating NS may be related to targets (MIF, SRC, and GBA) and metabolic pathways (citrate cycle, glyoxylate and dicarboxylate metabolism, alanine, aspartate and glutamate metabolism, and glycolysis/gluconeogenesis).