Plasma and urine metabonomics coupled with UPLC-Q-TOF/MS and multivariate data analysis on potential biomarkers in anemia and hematinic effects of steamed notoginseng

Abstract

The present study aimed to investigate the effects of steamed notoginseng single-flavored medicine, herb pairs, compound medicine on anemia rats induced by N-acetyl phenyl hydrazine (APH) to explore the underlying hematinic regulation mechanisms. Rats were randomly divided into seven groups: control group (CG); model group (MG); positive control group (PCG); steamed notoginseng group (SNG); ginseng group (GG); herbal pair group (HPG) and compound prescription group (CPG). Day 12 of the experiment, the blood routine examination of the rats was measured. At the same time, the rats' plasma and urine samples were collected. An Ultra-performance Liquid Chromatography-Quadrupole-Time-of-Flight / Mass Spectrometry (UPLC-Q-TOF/MS) with unsupervised principal component analysis (PCA) and supervised partial least squares discriminant analysis (PLS-DA) combined analytical method was established for metabolomics study of steamed notoginseng. Compared with the CG, red blood cell (RBC) and hemoglobin (Hb) levels in the MG were significantly lower (P < 0.01). The results of blood routine examination show that the model of the rats with blood deficiency syndrome have successfully modelled. Compared with the MG, steamed notoginseng can significantly increase the RBC level of rats (P < 0.01), indicating that steamed notoginseng has the blood tonic effect. The related indicators of each administration group showed a good trend of returning to normal. 44 potential biomarkers for hemolytic anemia were screened from plasma and urine samples. Compared with the CG, there were down-regulation seven biomarkers in plasma of the MG, such as retinol, l-valine and arachidonic acid, and 14 biomarkers up-regulated such as protoporphyrin IX and nicotinamide; 28 metabolites such as proline, histidine, phenylalanine, l-arginine and l-tyrosine were up-regulated in urine of the MG. The metabolic level of biomarkers could be changed to a normal state after the rats were given steamed notoginseng, herb pairs, and compound prescriptions. It is presumed that steamed notoginseng plays a role in blood enriching through 12 metabolic pathways, including valine, leucine and isoleucine biosynthesis, phenylalanine, tyrosine and tryptophan biosynthesis, retinol metabolism and so on.