A metabonomic strategy based on UHPLC–MS with principal component analysis was developed to investigate the intervention effects of Epimedium koreanum on metabolism characters of ‘Kidney-Yang Deficiency syndrome’ rats. The rats were injected intraperitoneally hydrocortisone once daily for 15 days to simulate ‘Kidney-Yang Deficiency syndrome’ and then administered orally E. koreanum extract once daily for the following 15 days. Plasma and urine samples before hydrocortisone injection, on day 15 of hydrocortisone injection and on days 3, 6, 9, 12, 15 exposed to E. koreanum extract were collected. Significant metabolic disorders were observed in ‘Kidney-Yang Deficiency syndrome’ rats and sixteen potential biomarkers were identified. The disturbed plasma levels of phenylalanine, tryptophan, cholic acid, lysophosphatidylcholines and urinary levels of phenylalanine, hippurate, phenylacetylglycine, N2-succinyl-l-ornithine, creatinine, α-ketoglutarate, citrate, phenol sulfate, indoxyl sulfate, cresol sulfate in model rats were gradually restored to normal after administration of E. koreanum extract, which indicated that E. koreanum had time-dependent recovering effects via regulating oxidant–antioxidant balance, amino acid metabolism, lipid metabolism, energy metabolism, and gut microflora. This work highlights that metabonomics is a promising tool for studying the essence of Chinese medicine's syndrome theory and the action mechanism of traditional Chinese medicine, and provides scientific and reasonable information on safety and efficacy of traditional Chinese medicine.Graphical abstractHighlights► This work integrated the plasma and urinary metabolic profilings. ► The plasma and urinary metabonomic analysis were complementary. ► This integrated method was developed to investigate effects of Epimedium koreanum. ► Seven potential biomarkers in plasma and ten in urine were identified. ► E. koreanum had recovering effects on ‘Kidney-Yang Deficiency syndrome’.

This paper was designed to study metabonomic characters of the ‘Kidney-Yang Deficiency syndrome’ induced by high dose of hydrocortisone and the therapeutic effects of Rhizoma Drynariae, classic traditional Chinese medicine (TCM) in treating the syndrome. A urinary metabonomics method based on ultra-performance liquid chromatography coupled with mass spectrometry (UPLC/MS) was developed. The significant difference in metabolic profiling was observed from model group (hydrocortisone-induced group) compared with the pre-dose group (rats before hydrocortisone inducing) by using the principal components analysis (PCA). The time-dependent regression tendency in Rhizoma Drynariae treatment group (hydrocortisone-induced rats followed by being administered with Rhizoma Drynariae ethanol extracts) from day 3 to 15 was obtained, indicating the time-dependent recovery effect of Rhizoma Drynariae on ‘Kidney-Yang Deficiency syndrome’ rats. Some significantly changed metabolites like phenylalanine, phenylacetylglycine, N2-succinyl-l-ornithine, l-proline, creatinine, hippurate and citrate have been identified. These biochemical changes are related to the disturbance in energy metabolism, amino acid metabolism and gut microflora, which are helpful to further understand the ‘Kidney-Yang Deficiency syndrome’ and the therapeutic mechanism of Rhizoma Drynariae. The work shows that the metabonomics method is a valuable tool for studying the essence of Chinese medicine's syndrome theory and therapeutic effect mechanism of TCM.