Investigation of the incompatibility of Knoxiae Radix and Glycyrrhizae Radix et Rhizoma in rats by 1 H NMR and MS-based untargeted metabolomic analysis.

Knoxiae Radix (HDJ, usually used after being processed into CHDJ) is a traditional Chinese herbal medicine that has been recorded in the Chinese Pharmacopoeia for many years. It is said that Glycyrrhizae Radix et Rhizoma (GC) is incompatible with HDJ, but this is unproven. In this work, nontargeted metabolomics experiments were performed on rats to evaluate the effect of the combination of the two herbals. For this, we conducted a 28-day administration in rats. The plasma, urine and kidney tissues were collected for a metabolomics study based on 1 H NMR and LC-MS. The OPLS-DA method was used to screen biomarkers. In addition, the KEGG Pathway database and MetaboAnalyst were used to find metabolic pathways. Twenty-two significant metabolites were identified. These metabolites were related to many metabolic pathways such as amino acid metabolism, synthesis and degradation of ketone bodies. Significant changes in urine creatinine levels revealed that CHDJ is nephrotoxic. When the GC-CHDJ mass ratio was 1, the toxicity was strengthened; when the GC-CHDJ' mass ratio was 3, the toxicity was alleviated. This is the first time that a metabolomics approach has been used to investigate the incompatibility of GC-CHDJ.