Effect of the traditional Chinese medicine tongxinluo on endothelial dysfunction rats studied by using urinary metabonomics based on liquid chromatography-mass spectrometry.

ABSTRACT

A urinary metabonomic method based on ultra-fast liquid chromatography coupled with ion trap-time of flight mass spectrometry (UFLC/MS-IT-TOF) was employed to study the preventive efficacy and the metabolic changes caused by simavastatin and the traditional Chinese medicine tongxinluo in endothelial dysfunction rats. Principal component analysis (PCA) was applied to study metabolic patterns of endothelial dysfunction rats and healthy control rats. 1-Methyladenosine, indoxyl sulfate, hippuric acid, riboflavin, coproporphyrin, and p-cresol glucuronide were identified as potential biomarkers, indicating that pathways of adenine, tryptophan, phenylalanine, riboflavin and porphyrin metabolism were disturbed in endothelial dysfunction rats. Applications of simvastatin and tongxinluo to endothelial dysfunction rats improved endothelial function according to the results of histopathology and measurements of endothelin-1 and nitric oxide. Metabonomic studies suggested that tongxinluo prevents endothelial dysfunction by regulating multiple metabolic pathways to their normal state, whereas simvastatin only altered selected metabolic pathways. This research demonstrated that metabonomics is a powerful and promising tool for disease investigation and the efficacy evaluation of complex traditional Chinese medicines.