High-throughput lipidomics enables discovery of the mode of action of huaxian capsule impacting the metabolism of sepsis

Abstract

Severe sepsis (SS) is a major cause of mortality and morbidity in the intensive care unit and requires rapid diagnosis and treatment. Lipids are key regulators of cellular function; hence, in this study, we hypothesized that lipid levels could be altered in patients suffering from SS. Lipidomics is the comprehensive analysis of molecular lipid species. In this study, we used an untargeted lipidomics approach coupled with multivariate data analysis and bioinformatics analysis to profile the metabolic changes of sepsis induced by cecal ligation and puncture (CLP) in rats and investigated the treatment effects of huaxian capsule (HXC), a herbal medicine with putative effects in SS treatment. Ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) and pattern recognition methods were employed to evaluate the metabolic phenotypic changes. Differentially expressed lipids have been further analyzed using the ingenuity pathway analysis (IPA) software, a tool that discloses functional pathways associated with lipids of interest. As a result, ten lipids involved in multiple metabolic pathways, such as in glycerophospholipid metabolism, ether lipid metabolism, purine metabolism, and tryptophan metabolism representing characteristic phenotypes, were identified by pathway analysis. HXC administration can reverse lipid phenotype changes induced by CLP; this indicates that the effectiveness of HXC as an SS treatment depends on modulation of the lipid metabolic changes. Our study shows that lipidomics is a valuable method that can provide additional insight into the underlying mechanisms of HXC in the SS treatment.