Metabolomic characteristics of spontaneously hypertensive rats under chronic stress and the treatment effect of Danzhi Xiaoyao Powder, a traditional Chinese medicine formula / 中西医结合学报

OBJECTIVE@#Numerous studies have demonstrated the close relationship between chronic stress and blood pressure (BP). Hypertensive subjects exhibit exaggerated reactions to stress, especially higher BP. The mechanisms by which stress affects pre-existing hypertension still need to be explored. Danzhi Xiaoyao Powder (DP), a historical traditional Chinese medicine formula, is a promising treatment for BP control in hypertensive patients under stress. The present study investigated the metabolomic disruption caused by chronic stress and the treatment effect and mechanism of DP.@*METHODS@#Spontaneously hypertensive rats (SHRs) were subjected to chronic restraint stress (CRS) for 4 weeks. BP was measured via the tail-cuff method, and anxiety-like behavior was quantified using the elevated-plus-maze test. Meanwhile, DP was administered intragastrically, and its effects were observed. Global metabolomic analysis was performed using ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry, followed by multivariate statistical analysis to detect differential metabolites and pathways.@*RESULTS@#DP alleviated the CRS-induced increase in BP and anxiety-like behavior. Systematic metabolic differences were found among the three study groups. A total of 29 differential plasma metabolites were identified in both positive- and negative-ion modes. These metabolites were involved in triglyceride metabolism, amino acid (phenylalanine, tryptophan, and glycine) metabolism, and steroid hormone pathways.@*CONCLUSION@#These findings expose the metabolomic disturbances induced by chronic stress in SHRs and suggest an innovative treatment for this disorder.

Overview of Metabolomics in Research of Hypertension / 中国实验方剂学杂志

Hypertension is one of the most common chronic diseases, also an important risk factor for a series of cardio-and cerebra-vascular diseases. Due to its polygenic, multi-factorial nature and heterogeneity, the underlying cause has not been fully elucidated, satisfied therapeutic effect hasn't been totally achieved either. Metabolomics is used to evaluate metabolic changes of organisms from a holistic perspective, associating with biological processes to reveal the whole situation of the body. In recent years, researchers have used metabolomics to study the pathogenesis of hypertension, potential biomarkers, effects of lifestyle interventions, and mechanisms of antihypertensive drugs. Targeted or untargeted ways are applied to study metabolites form blood, urine, or tissues of human or animals. Metabolic pathways of gut microflora, oxidative stress, fatty acids, and amino acids have drawn more attention, and the discovered metabolites may become potential biomarkers, further the diagnostic biomarkers and treatment targets. In addition, traditional Chinese medicine (TCM) is an integrated complex system in syndrome diagnosis and treatment, and metabolomics coincides well with the concepts of it. TCM researchers also use this method to study the biological basis of syndromes in hypertension and the mechanism of antihypertensive Chinese medicine. There are significant differences in the metabolites between different syndromes. TCM treatments can restore the metabolite disturbance caused by high pressure, which is probably one of the pharmacological pathways of antihypertensive Chinese medicine. Metabolomic studies in hypertension have achieved great progress, but there're still challenges in data analysis, integration with other metabolomic studies and other omic studies and causal relationship in further study.