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

Abstract

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 years. It is said that Glycyrrhizae Radix et Rhizoma (GC) is incompatible with HDJ, but few studies can prove this. In this work, non‐targeted 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 metabolomics study based on ¹H 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. 22 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 was nephrotoxic. When GC‐CHDJ’s mass ratio was 1, the toxicity was strengthened; when GC‐CHDJ’s mass ratio was 3, the toxicity was alleviated. This is the first time that metabolomics approach has been performed to investigate the incompatibility of GC‐CHDJ.