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.

[Anti-depressant effect and mechanism of supercritical CO2 extract from Compound Chaigui Fang].

The tail suspension test (TST), forced swimming test (FST) and chronic unpredictable mild stress (CUMS) model were used to evaluate the anti-depressant effect of supercritical CO2 extract from Compound Chaigui Fang (FFCGF). A nuclear magnetic resonance (NMR)-based metabonomics combined with multivariate statistical analysis was performed to explore the mechanism of FFCGF. Rats were conducted by CUMS procedure for 28 days and drugs were administrated at the same time. The body weight, sucrose preference, crossings and rearings in open-field tests were evaluated and the urine was collected simultaneously. The metabonomic profiles of rats' urine were analyzed by NMR and potential biomarkers were searched by multivariate statistical analysis. The results showed that administration of FFCGF significantly decreasing the immobility time in FST and TST and improving rats' body weight, sucrose preference, crossings and rearings in CUMS, which were indication that the anti-depressant effect of FFCGF was abvious. Significant differences in the metabolic profile of the CUMS treated group and the control group were observed, which were consistent with the results of behavioral tests. Decreased levels of acetic acid, succinic acid, 2-oxidation glutaric acid and citric acid and increased glycine and pyruvic acid in urine were significantly affected by the CUMS procedure and the 6 biomarkers were reversed evidently after administration of FFCGF. These changes were suggestion that the anti-depressant mechanism of FFCGF was associated with energy metabolism, lipid metabolism and amino acid metabolism.

Analysis of the restorative effect of Bu-zhong-yi-qi-tang in the spleen-qi deficiency rat model using (1)H-NMR-based metabonomics.

ETHNOPHARMACOLOGICAL RELEVANCE: Bu-zhong-yi-qi-tang (BT) is a classical formula for the treatment of spleen-qi descending, visceroptosis with hyposplenic qi, uterine prolapse, and rectal prolapse due to chronic diarrhea in traditional Chinese medicine (TCM) and has been identified as an effective drug for the treatment of TCM spleen-qi deficiency in clinical practice. The present study aimed to investigate the restorative effect and the potential mechanisms of Bu-zhong-yi-qi-tang in a rat spleen-qi deficiency model using (1)H-NMR-based metabonomics. MATERIALS AND METHODS: The rat spleen-qi deficiency model was established as follows: oral administration of Radix Rhei extract (equivalent to 10g/kg body weight of the crude drug), loaded swimming, and starvation for 24h. Each of these treatments was administered consecutively every three days. Sixty male SD rats were randomly divided into five groups, and three of the groups received a different oral dose of the aqueous extract of Bu-zhong-yi-qi-tang during the last seven days of the three-week experimental period. The body weight and motor behavior of the rats were measured and recorded once a week. The endogenous metabolites in the plasma were analyzed using NMR in conjunction with multivariate and statistical techniques. In addition, the liver and spleen were removed and weighed. RESULTS: All of the rats in the spleen-qi deficiency group presented pasty loose stools, inactiveness, grouping, a decrease in swimming endurance, and lackluster, loose, and disorderly behavior in addition to a significant decrease in body weight, spleen weight, and liver weight. In contrast, the abovementioned demonstrations were reversed to a certain extent in the rats treated with Bu-zhong-yi-qi-tang compared with the model group (p<0.05, p<0.01). A significant separation was determined between the control and model groups in the PCA score plot, which indicates that the spleen-qi deficiency model was successfully duplicated. The changes in the levels of endogenous metabolites in the plasma included lower levels of valine, leucine, and O-acetyl-glycoprotein and a higher concentration of lactate in the spleen-qi deficiency group compared with the control group. Treatment with Bu-zhong-yi-qi-tang at least partially returned the levels of these metabolites to the normal levels. CONCLUSIONS: The restorative effects of Bu-zhong-yi-qi-tang in rats with spleen-qi deficiency were confirmed, and four endogenous metabolites were identified as potential biomarkers of the symptoms of spleen-qi deficiency and most likely play roles in the changes observed in certain metabolic pathways, such as the energy, protein, and glycolytic metabolisms.