Abstract

Hypertension is one of the most common cardiovascular diseases, resulting in serious complications such as cardiovascular damage and chronic kidney disease. Tianshu capsule (TSC), composed of Chuanxiong (Ligusticum chuanxiong Hort) and Tianma (Gastrodiaelata Blume), has been widely used to treat the blood stasis type of headache and migraine in clinic. Results of previous research showed its antihypertensive effects, but the underlying mechanisms were still unclear. The purpose of this study was to evaluate the antihypertensive effect of TSC on spontaneously hypertensive rats by 1H NMR-based metabonomics and enzyme-linked immunosorbent assay (ELIAS), explore potential biomarkers and targets, and probe the potential mechanism of TSC on antihypertensive treatment. The results showed that TSC could decrease the product of oxidative stress (MDA) and enhance the activities of SOD and GSH-Px, down-regulate the expression of enzymes (LDHA, PKM2 and HK2) related to glycolysis, and perturb the levels of a series of amino acids (isoleucine, alanine, asparagine, citrate, etc.) and pathways. Multivariate statistical analyses showed remarkable changes in some endogenous metabolites after administrating TSC related to oxidative stress, amino acid metabolism and energy metabolism disturbances. Some enzymes (alanine-glyoxylate aminotransferase-2, tyrosine hydroxylase, dopa decarboxylase, etc.) related to metabolic biomarkers were predicted as the potential targets of TSC treatment on SHRs. The discoveries are helpful to understand the antihypertensive mechanism of TSC and provide theoretical evidence for its future research, development and clinical use.

Highlights

  • Hypertension is the main cause of morbidity and mortality of cardiovascular diseases

  • Tianshu capsule (TSC) is composed of Ligusticum chuanxiong Hort (Chuanxiong in China) and Gastrodia elata Blume (Tianma in China) with a crude weight ratio of 4:1

  • Pharmacological studies have shown that ferulic acid possess anti-oxidant, anti-inflammatory, anti-thrombus and cardiovascular protection, free radical scavenging and blood pressure-lowering effects (Barone et al, 2009; Zhang et al, 2010; Commission, 2015)

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Summary

Introduction

Hypertension is the main cause of morbidity and mortality of cardiovascular diseases. It was described as one of the most common serous chronic diseases for global burden in 2013 (Collaborators et al, 2015). The cause of 90% of hypertension was still unclear as a result of its complex, multifactorial and polygenic character, and it was defined as essential hypertension. Essential hypertension is a risk associated with development of cardio-cerebrovascular disease. Common treatment with anti-hypertensive medications could reduce the blood pressure and major cardiovascular event risks. TCM has a long history for clinical use and could be one of the most effective sources for new drug development

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