Metabonomics and Molecular Biology-based Effects of Sugemule-3 in an Isoproterenol-induced Cardiovascular Disease Rat Model

Cardiovascular disease(CVD) is a common and serious disease in the elderly, which has characteristically high prevalence, disability, and mortality rates. However, the etiology of CVD is still not very clear. The traditional Mongolian medicine Sugemule-3(SM) is usually used for the treatment of CVD and exhibits a good curative effect. In this study, a serum metabolite profile analysis was used to identify potential biomarkers associated with isoproterenol(ISO)-induced CVD and investigate the mechanism of the action of SM. Ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS) was used for the metabono-mics analysis. Principal component analysis(PCA) was used to process the acquired data to differentiate the results of the control, CVD, and SM treatment groups. Orthogonal partial least squares discriminant analysis(OPLS-DA) enabled the identification of 21 metabolites as potential biomarkers that were relevant to phospholipid and energy metabolism. The results indicate that SM played a protective role against ISO-induced CVD in rats by regulating phospholipid and energy metabolic pathways. Further, we verified the apoptotic metabolic pathway using molecular biology methods, such as terminal deoxynucleotidyl transferase(TdT) deoxyuridine 5'-triphosphate(dUTP) nick-end labeling(TUNEL) assay and Western blot analysis. Furthermore, this study identified early biomarkers of CVD and elucidated the underlying mechanism of the therapeutic actions of SM, which is worth further to be investigated for development as a clinical therapy.