A GC-MS urinary quantitative metabolomics analysis in depressed patients treated with TCM formula of Xiaoyaosan.

Xiaoyaosan, one of the best-known traditional Chinese medicine prescriptions, has been widely used in China for the treatment of mental disorders such as depression. Although both clinical application and animal experiments indicate that Xiaoyaosan has an obvious antidepressant effect, the mechanism still remains unclarified, and there are few studies quantitatively measured the biomarkers of Xiaoyaosan treatment by metabolomics to determination. In this study, 25 depressed patients and 33 healthy volunteers were recruited. A GC-MS based metabolomics approach and the multivariate statistical methods were used for analyzing the urine metabolites of depressed patients before and after treatment compared with healthy controls. Then the biomakers through metabolomics determination were carried out the quantitative analysis. In total, 5 metabolites were identified as the potential diseased and therapeutic biomarkers of depression and Xiaoyaosan. Alanine, citrate and hippurate levels were significantly increased in the urine samples from depressed patients compared with healthy controls, while phenylalanie and tyrosine levels were significantly decreased. However, after Xiaoyaosan treatment for 6 weeks, phenylalanie and tyrosine levels were significantly increased (p<0.05) and alanine, citrate and hippurate levels significantly decreased (p<0.05). Xiaoyaosan has a good priority on the treatment of depression and the ability to adjust the neurotransmitters to obtain the best treated response and also could regulate the metabolism of amino acids and promote to produce energy meet the needs of the body.

Investigation on the antidepressant effect of sea buckthorn seed oil through the GC-MS-based metabolomics approach coupled with multivariate analysis.

Depression is one of the prevalent and serious mental disorders and the number of depressed patients has been on the rise globally during the recent decades. Sea buckthorn seed oil from traditional Chinese medicine (TCM) is edible and has been widely used for treatment of different diseases for a long time. However, there are few published reports on the antidepressant effect of sea buckthorn seed oil. With the objective of finding potential biomarkers of the therapeutic response of sea buckthorn seed oil in chronic unpredictable mild stress (CUMS) rats, urine metabolomics based on gas chromatography-mass spectrometry (GC-MS) coupled with multivariate analysis was applied. In this study, we discovered a higher level of pimelic acid as well as palmitic acid and a lower level of suberic acid, citrate, phthalic acid, cinnamic acid and Sumiki's acid in urine of rats exposed to CUMS procedures after sea buckthorn seed oil was administered. These changes of metabolites are involved in energy metabolism, fatty acid metabolism and other metabolic pathways as well as in the synthesis of neurotransmitters and it is helpful to facilitate the efficacy evaluation and mechanism elucidating the effect of sea buckthorn seed oil for depression management.

Research on the Pathological Mechanism and Drug Treatment Mechanism of Depression.

Depression is one of the prevalent and persistent psychiatric illnesses. It brings heavy socioeconomic burden such as healthcare expenditures and even higher suicide rates. Despite many hypotheses about its mechanism have been put forward, so far it is still unclear, not to mention the precise and effective diagnostic or therapeutic methods. In this paper, the current conditions of pathological and pharmacological mechanism of depression were reviewed systematically. Firstly, the most recent hypotheses and metabolomics based research including hereditary, neurotransmitter systems, brain derived neurotrophic factor (BDNF), hyperactivity of the hypothalamic pituitary adrenal (HPA) axis and inflammatory as well as metabolomics were summarized. Secondly, the present situation and development on antidepressant drugs at home and abroad were reviewed. Finally, a conclusion and prospect on the pathological and pharmacological mechanism of depression were provided primarily.

Dynamic analysis of the endogenous metabolites in depressed patients treated with TCM formula Xiaoyaosan using urinary (1)H NMR-based metabolomics.

ETHNOPHAMACOLOGICAL RELEVANCE: Xiaoyaosan (XYS), one of the best-known traditional Chinese medicine prescriptions with a long history of use, is composed of Bupleurum chinense DC., Paeonia lactiflora Pall., Poria cocos (Schw.) Wolf, Angelica sinensis (Oliv.) Diels, Zingiber officinale Rosc., Atractylodes macrocephala Koidz., Glycyrrhiza uralensis Fisch., and Mentha haplocalyx Briq. For centuries, XYS has been widely used in China for the treatment of mental disorders such as depression. However, the complicated mechanism underlying the antidepressant activity of XYS is not yet well-understood. This understanding is complicated by the sophisticated pathophysiology of depression and by the complexity of XYS, which has multiple constituents acting on different metabolic pathways. The variations of endogenous metabolites in depressed patients after administration of XYS may help elucidate the anti-depressant effect and mechanism of action of XYS. The aim of this study is to establish the metabolic profile of depressive disorder and to investigate the changes of endogenous metabolites in the depressed patients before and after the treatment of Xiaoyaosan using the dynamic analysis of urine metabolomics profiles based on (1)H NMR. MATERIALS AND METHODS: Twenty-one depressed patients were recruited from the Traditional Chinese Medicine Department of the First Affiliated Hospital of Shanxi Medical University. Small endogenous metabolites present in urine samples were measured by nuclear magnetic resonance (NMR) and analyzed by multivariate statistical methods. The patients then received XYS treatment for six weeks, after which their Hamilton Depression Scale (HAMD) scores were significantly decreased compared with their baseline scores (p≤0.01). Eight components in urine specimens were identified that enabled discrimination between the pre- and post-XYS-treated samples. RESULTS: Urinary of creatinine, taurine, 2-oxoglutarate and xanthurenic acid increased significantly after XYS treatment (p≤0.05), while the urinary levels of citrate, lactate, alanine and dimethylamine decreased significantly (p≤0.05) compared with pre-treatment urine samples. These statistically significant perturbations are involved in energy metabolism, gut microbes, tryptophan metabolism and taurine metabolism. CONCLUSIONS: The symptoms of depression had been improved after 6 weeks׳ treatment of XYS according to evaluation of HAMD scores. The dynamic tendency of the 8 metabolites that changed significantly during the treatment of XYS is consistent with the improvement in symptoms of depression. These metabolites may be used as biomarkers for the diagnosis of depressive disorders or the evaluation of the antidepressant as well as the exploration of the mechanism of depression.

[1H NMR based metabonomics study on the antidepressant effect of genipin in rat hippocampus].

The purpose of this study is to explore depression metabolic markers in rat hippocampus and to investigate the anti-depressant effect of genipin and its mechanisms using nuclear magnetic resonance (NMR) metabonomics. Chronic unpredictable mild stress (CUMS) procedure was conducted to establish the depressive rat model. At the beginning of the third week, genipin low dose (25 mg x kg(-1)), middle dose (50 mg x kg(-1)), high dose (100 mg x kg(-1)), and venlafaxine (50 mg x kg(-1)) were given to the CUMS rats separately once daily for two weeks except control and model groups. Rat hippocampus was analyzed by 1H NMR based metabonomics after drug administration for 2 weeks. Significant differences in the metabolic profile of rat hippocampus of the CUMS treated group and the control group were observed with metabolic effects of CUMS including decreasing in glycine and N-acetylaspartate, increasing in inositol, glutamate, lactate, glutamine, taurine and alanine. Genipin showed ideal antidepressive effects at a dose of 50 mg x kg(-1) in rats, decrease of inositol, glutamate, lactate, alanine were observed, while glycine and N-acetylaspartate were increased. Important influence has been found on normal nervous system function of these significant changed metabolites, which suggests that the antidepressant effect of genipin may be played by enhancing the activity of neurons in hippocampus, repairing and improving the function of the neuron. The metabonomics approach is an effective tool for the investigation of the anti-depressant effect and pharmacologic mechanisms of genipin.