High-throughput metabolomics for evaluating the efficacy and discovering the metabolic mechanism of Luozhen capsules from the excessive liver-fire syndrome of hypertension

RSC Adv. 2019 Oct 9;9(55):32141-32153. doi: 10.1039/c9ra06622e. eCollection 2019 Oct 7.

Abstract

Essential hypertension (EH) is a chronic disease characterized by a variety of causes of elevated systemic arterial pressure, which often causes functional or organic damage to important organs such as the heart, brain, and kidney. Hypertension of excessive liver-fire syndrome is a type of classification for young people with essential hypertension. The disease is slower in its onset and its symptoms are more ambiguous, and thus its pathogenesis is complicated and still unclear. In this study, aconite, dried ginger and cinnamon extracts were combined with l-NAME to establish a model of excessive liver-fire hypertension. Blood pressure (systolic blood pressure), ANGII, NE and 5-HT were used as evaluation indicators to establish the model. Urinary metabolomics based on ultra-high performance liquid chromatography coupled with quadruple time-of-flight mass spectrometry was used to characterize the metabolic changes and potential biomarkers in modeled rats. Compared to the treatment group, 32 potential biomarkers were initially identified in the model using multivariate statistical analysis involving 11 metabolic pathways. After oral administration of Luozhen capsules, eight biomarkers that can be adjusted in high, medium and low doses of Luozhen capsules in urine were preliminarily determined, mainly involving two metabolic pathways of amino acid metabolism and lipid metabolism. In conclusion, this study explored the metabolomic changes in rats with hypertension of liver-fire hyperactivity syndrome and the post-dose metabolomics, determined the relevant biomarker groups, and clarified the metabonomic connotation of Luozhen capsules in the treatment of liver-fire excessive type hypertension.