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Proton nuclear magnetic resonance (1H NMR) based metabolomics was applied to characterize the fecal metabolic profiles of chronic unpredictable mild stress (CUMS)-depression (CUMS-D) and CUMS-resilience (CUMS-R) rats. The fecal biomarkers and metabolic pathways involved in CUMS-D and CUMS-R were screened and identified, revealing the underlying mechanisms of two different responses of the body to the same stresses. Firstly, the classic depression model, i.e. CUMS, was constructed. According to the fecal metabolomics profiles, the model rats were divided into two groups, i.e. the CUMS-D group and the CUMS-R group. And then, the depression statuses of CUMS-D rats and CUMS-R rats were verified by their sucrose preference rates. Lastly, multivariate data analysis was applied to clarify the fecal biomarkers and corresponding metabolic pathways involving in CUMS-D and CUMS-R. The results show that compared with the control rats, the sucrose preference rates of CUMS-D rats were significantly reduced. By contrast, the sucrose preference rates of CUMS-R rats had no significant difference. At the same time, CUMS-D and CUMS-R showed both unique and shared biomarkers and pathways. Three pathways are significantly related to CUMS-D, including taurine and hypotaurine metabolism, alanine, aspartate and glutamate metabolism, and arginine and proline metabolism. Glycerolipid metabolism and tryptophan metabolism are specific pathways related to CUMS-R. This study explores the mechanisms of the emergence of susceptible and resilience of rats under the same stimulus from a metabolomics perspective. The current findings provide not only a new perspective for studying depression, and personalized and precision treatments in clinic, but also the research and development of antidepressants.
ABSTRACT
This study aimed to explore the mechanism of Xiaoyao San(XYS) in the treatment of three diseases of liver depression and spleen deficiency, ie, depression, breast hyperplasia, and functional dyspepsia, and to provide a theoretical basis for the interpretation of the scientific connotation of "treating different diseases with the same method" of traditional Chinese medicines. Traditional Chinese medicine systems pharmacology database and analysis platform(TCMSP) was used to screen the active components of XYS which underwent principal component analysis(PCA) with the available drugs for these three diseases to determine the corresponding biological activities. The targets of XYS on depression, breast hyperplasia, and functional dyspepsia were obtained from GeneCards, TTD, CTD, and DrugBank databases. Cytoscape was used to plot the "individual herbal medicine-active components-potential targets" network. The resulting key targets were subjected to Kyoto encyclopedia of genes and genomes(KEGG) pathway analysis and gene ontology(GO) enrichment analysis. A total of 121 active components of XYS and 38 common targets in the treatment of depression, breast hyperplasia, and functional dyspepsia were collected. The key biological pathways were identified, including advanced glycation and products(AGEs)-receptor for advanced glycation and products(RAGE) signaling pathway in diabetic complications, HIF-1 signaling pathway, and cancer-related pathways. The key targets of XYS in the treatment of depression, breast hyperplasia, and functional dyspepsia included IL6, IL4, and TNF, and the key components were kaempferol, quercetin, aloe-emodin, etc. As revealed by the molecular docking, a strong affinity was observed between the key components and the key targets, which confirmed the results. The therapeutic efficacy of XYS in the treatment of diseases of liver depression and spleen deficiency was presumedly achieved by reducing the inflammatory reactions. The current findings are expected to provide novel research ideas and approaches to classify the scientific connotation of "treating different diseases with the same method" of Chinese medicines, as well as a theoretical basis for understanding the mechanism of XYS and exploring its clinical applications.
Subject(s)
Humans , Depression/drug therapy , Drugs, Chinese Herbal/pharmacology , Dyspepsia/drug therapy , Hyperplasia/drug therapy , Medicine, Chinese Traditional , Molecular Docking SimulationABSTRACT
This work investigates the effects of Guilingji (GLJ) on D-galactose-induced aging and changes in serum metabolites by UHPLC-Q exactive orbitrap-MS in rats. The rat model of aging by subcutaneous injection of D-galactose (300 mg·kg-1) was used to analyze the effect of different concentrations of GLJ (37.5, 75, 150 mg·kg-1) on an open field test in aging rats. Rat serum was collected after 8 weeks and subjected to LC-MS to analyze the anti-aging effect of GLJ. Animal experimentation was approved according to the Committee on the Ethics of Animal Experiments of Shanxi University (SXULL2014032). GLJ significantly improved the autonomous activity of rats. Compared with the control group, 23 metabolites in the treated group changed significantly, involving three main pathways. The group that was given GLJ had altered regulation of 4 serum metabolites in two pathways. Our results indicate that GLJ can delay aging behavior in rats; the mechanism of this anti-ageing effect remains to be determined.
ABSTRACT
Objective To explore the effects of Guilingji on improving learning and memory dysfunction caused by aging. Methods The mouse model of subacute aging caused by D-galactose and the rat model of natural aging were used respectively to imitate learning and memory dysfunction caused by aging. The effects of Guilingji on improving of learning and memory function index were focused in the diving platform experiment and the Morris water maze experiment. At the same time, the effect of that on rat organ index and blood biochemical index were investigated. Results Guilingji can significantly prolong step down latency (P < 0.05) and reduce the number of errors within 5 min (P < 0.05, 0.01) of the model mice. It can shorten positioning navigation escape incubation period (P < 0.01), extend the space exploration quadrant retention time (P < 0.05, 0.01), and increase the number of access to the platform (P < 0.05). Guilingji can increase testicular, thymus and spleen index (P < 0.05) and reduce the ALT content in serum (P < 0.05). Conclusion Guilingji can obviously improve the impairment of learning and memory function caused by aging. It also has some good effects on enhancing immunity, improving reproductive capacity, and protecting liver.
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Objective: To analyze and explore the changes of the metabolites in serum and urine of the chronic unpredictable depression rat model (CUMS) rats disturbed by seabuckthorn seed oil with using nuclear magnetic resonance spectroscopy (1H-NMR) and KEGG database. Methods: CUMS was prepared and the rats seabuckthorn seed oil was ig given to intervene at the same time for four weeks. Then the serum and the urine of rats were collected to test by 1H-NMR based metabolomics approach which purpose was to analyze the changes of the metabolites. Finally, the KEGG database was searched to analyze metabolic pathway. Results: A total of 17 metabolites were identified as potential biomarkers in serum and urine for the CUMS model, of which nine metabolites were found in serum including higher levels of lipids, β-OH-butyrate, lactate, and N-acetyl glycoprotein and lower levels of alanine, betaine, trimethylamine N-oxide, α-glucose, and β-glucose and eight metabolites were found in urine including level increments for succinate, aspirate and level reductions for acetate, 2-oxoglutaric acid, citrate, TMA, betaine, and phenylalanine, compared with the negative control group (NS). After intervened by seabuckthorn seed oil, the above different metabolites have appeared different degree of callback, closing to NS. Conclusion: These metabolic responses to CUMS treatment by seabuckthorn seed oil seemed to be some alterations in energy metabolism, lipid metabolism, amino acid metabolism, methylamine metabolism, and synthesis of neurotransmitter.
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<p><b>OBJECTIVE</b>To observe the effect of Dingguier umbilical paste on rats with functional dyspepsia and mice with splenic asthenia, and investigate the related mechanism.</p><p><b>METHOD</b>Functional dyspepsia models of rats were made by irregular food intake plus diluted hydrochloric acid. Successional treatments were offered for 14 days. The rats weights, contents of serum NO, AChE and MC were measured. The rats with splenic asthenia were made by rhubarb feed, and observed the affection of gastric emptying.</p><p><b>RESULT</b>Compared with those in the model control group, the weight of rats in all dosages Dingguier umbilical paste groups increased obviously (P < 0.05), pepsin activity of rats in the dosage (1.34 g x kg(-1)) Dingguier umbilical paste groups was significantly higher and the contents of NO and quantities of MC in the dosage (2.67 g x kg(-1)) Dingguier umbilical paste groups decreased clearly (P < 0.05), and the contents of serum AChE in all dosages Dingguier umbilical paste groups rose apparently. The weight of mice with splenic asthenia increased obviously, accelerated gastric emptying, and improved the symptom.</p><p><b>CONCLUSION</b>Dingguier umbilical paste has significant improvement of indigestion. The related mechanism may be to reduce the content of serum NO and the quantity of MC and enhance the content of serum AChE.</p>