Urinary UPLC-MS metabolomics dissecting the underlying mechanisms of Huaxian capsule protects against sepsis

Abstract

Severe sepsis (SS) remains a worldwide threat, not only in industrialized countries but also in developing countries. Currently, the incidence of SS is rising, and there is a lack of effective drugs. Huaxian capsule (HXC) is traditional Chinese medicine with therapeutic effects on SS. The objectives of this study were to explore the underlying mechanisms of pharmacological effects of HXC on the treatment of SS. Metabolomics is a powerful tool for the characterization of metabolic phenotypes, potential metabolite biomarkers and metabolic pathways. Here, we investigated the metabolic changes in SS rats by performing metabolic profiling and metabolite biomarkers. Urinary UPLC-MS coupled with multivariate statistical analysis including principal components analysis (PCA), partial least-squares discriminant analysis (PLS-DA), and orthogonal projections to latent structures discriminant analysis (OPLS-DA) were used to assess phenotypic changes. Metabolites contributing to the discrimination the control group, SS group and HXC group were identified by using unsupervised PCA. Metabolic pathway analysis was performed using the MetPA web tool. As a result, 10 potential metabolite biomarkers in urine involved phenylalanine, tyrosine and tryptophan biosynthesis, valine, leucine and isoleucine biosynthesis, glycine, serine and threonine metabolism, tyrosine metabolism pathways, were identified in SS rats. The unsupervised PCA score plot showed that the HXC group cluster modulating dynamic metabolic changes was closer to that of the control group than the model group cluster, demonstrating that HXC has therapeutic effects on SS rats. Overall, it showed that urinary UPLC-MS metabolomics could dissect the underlying mechanisms of HXC protects against SS.