Anti-depressant effects of Xiaoyaosan on rat model of chronic unpredictable mild stress: a plasma metabonomics study based on NMR spectroscopy.

OBJECTIVES: To investigate the antidepressant effects of Xiaoyaosan (XYS) in a chronic unpredictable mild stress (CUMS) depression model. METHODS: The changes in behaviour and plasma metabolic profiles were investigated after four-week CUMS exposure and treatment. Drugs were administered during the four-week period of CUMS, with the healthy group serving as negative controls, and the fluoxetine and venlafaxine groups serving as positive controls. Plasma samples were collected at 28th day, and the plasma metabolic profiling was measured using NMR, followed by multivariate analysis. KEY FINDINGS: Exposure to CUMS for four weeks caused depression-like behaviour in rats, as indicated by significant decreases in weight gain, sucrose consumption and locomotor activity. Eleven potential biomarkers, including seven in the Carr-Purcell-Meiboom-Gill spectra, five in the diffusion-edited spectra, and one in both were identified. It was found that trimethylamine-N-oxide, alanine, ß-hydroxybutyrate, valine, leucine/isoleucine, low-density lipoprotein/very low-density lipoprotein and lipids were lower and phosphatidylcholine, high-density lipoprotein, choline and N-acetyl glycoproteins were higher in CUMS-treated rats, as compared with controls. XYS significantly suppressed behavioural changes and attenuated plasma metabolite changes. CONCLUSIONS: XYS produced an obvious antidepressant effect, and the metabonomic approach benefits estimation of the pharmacodynamic action of traditional Chinese medicine prescriptions.

Urinary metabonomic study using a CUMS rat model of depression.

Chronic unpredictable mild stress (CUMS) is a well-validated model of depression. In this study, a urinary metabonomics method based on the NMR spectrometry was used to study the metabolic perturbation in CUMS-induced rat depression model. With pattern recognition analysis, a clear separation of CUMS rats and healthy controls was achieved, and nine endogenous metabolites contributing to the separation were identified. CUMS-treated rats were characterized by the increase of glycine, pyruvate, glutamine, and asparagines, as well as the decrease of 2-oxoglutarate, dimethylglycine, citrate, succinate, and acetate. The urinary biochemical changes related to the metabolic disturbance in CUMS induced depression, and the possible correlations with live qi stagnation in traditional Chinese medicine are discussed. The work shows that CUMS is a reliable model for studying depression, and the noninvasive urinary metabolomic method is a valuable tool to investigate the biochemical pertubations in depression as an early diagnostic means.

[Experimental study on metabonomics of coronary heart disease myocardial ischemia of blood stasis syndrome based on the NOESY pulse NMR].

OBJECTIVE: To study changes of serum metabolite profiles in Ameriod ring induced coronary heart disease (CHD) chronic myocardial ischemia (CMI) mini-pigs by NMR. METHODS: The blood stasis syndrome (BSS) animal model was established by coronary angiography, blood hemorheology, and so on. By using NMR and pattern recognition, changes of serum endogenous metabolites of the four-week mini-pigs of the BSS model and the sham-operative group. RESULTS: The model prepared by using this method was confirmed as the stable CHD CMI model of BSS. Animals in the model group and the sham-operative group were clearly classified using the principal component analysis (PCA). The PCA of serum 1HNMR spectrum and metabolic spectrum in the two groups were significantly different in this model. Compared with the sham-operative group, endogenous metabolites in the serum such as the levels of citric acid, beta-hydroxybutyrate, gamma-aminobutyric acid, lactic acid, glutamate, glucose, etc. increased in the model group, while the concentrations of lipid metabolites such as low-density lipoprotein (LDL) and very low-density lipoprotein (VLDL) decreased. CONCLUSIONS: The different metabolites between the model group and the sham-operative group mainly manifested as metabolic disorders of glucose and lipids, as well as energy metabolism such as the disturbance of tricarboxylic acid (TCA). Metabonomics could provide a new path for the objectivity of Chinese medicine syndromes.