An NMR Metabolomics Investigation of Perturbations after Treatment with Chinese Herbal Medicine Formula in an Experimental Model of Sepsis

Abstract

Sepsis is a leading cause of morbidity and mortality in critically ill patients. OMICS and systems pharmacology approaches offer the promise of new therapeutic candidates for the treatment of patients with sepsis. Qin-Re-Jie-Du (QRJD) and Liang-Xue-Huo-Xue (LXHX) are two traditional Chinese herbal medicine (CHM) formulas with putative effects in sepsis treatment. The present study aimed to assess their efficacy in an experimental model of sepsis in rats (cecal ligation and punctures) and investigate their mechanism of action using a 1H-NMR metabolomics approach. Rats were randomly divided into four groups (i.e., model group, sham control group, and two CHM treatment groups). Water extracts of QRJD and LXHX were orally administered to the two CHM treatment groups at a dose of 24 g/kg of body weight, once daily for 3 consecutive days. The same volume of 0.9% saline solution was orally administered to the model and sham surgery groups. Plasma samples were collected and measured using 600 MHz 1H-NMR spectroscopy. As a result, 18 potential metabolite biomarkers involved in multiple metabolic pathways, including increased energy metabolism, fat mobilization, and disrupted amino acid metabolism, were identified in septic rats. The principal component analysis (PCA) and partial least squares discriminant (PLS-DA) plots of the metabolic state correlated well with the mortality and clinical biochemistry results. An analysis of potential biomarkers verified the holistic effects of the two CHM formulas. The Cori cycle was positively regulated in the QRJD-treated formulas treatment group but also inhibited in the LXHX-treated group, which demonstrates the different efficacies of these solutions in septic rats.