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. 2013 Sep 18;8(9):e75721.
doi: 10.1371/journal.pone.0075721. eCollection 2013.

1H-NMR-based metabonomic studies on the anti-depressant effect of genipin in the chronic unpredictable mild stress rat model

Jun-Sheng Tian  1 , Bi-Yun Shi, Huan Xiang, Shan Gao, Xue-Mei Qin, Guan-Hua Du
Affiliations

1H-NMR-based metabonomic studies on the anti-depressant effect of genipin in the chronic unpredictable mild stress rat model

Jun-Sheng Tian et al. PLoS One. .

Abstract

The purpose of this work was to investigate the anti-depressant effect of genipin and its mechanisms using (1)H-NMR spectroscopy and multivariate data analysis on a chronic unpredictable mild stress (CUMS) rat model. Rat serum and urine were analyzed by nuclear magnetic resonance (NMR)-based metabonomics after oral administration of either genipin or saline for 2 weeks. 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. Metabolic effects of CUMS included decreases in serum trimetlylamine oxide (TMAO) and β-hydroxybutyric acid (β-HB), and increases in lipid, lactate, alanine and N-acetyl-glycoproteins. In urine, decreases in creatinine and betaine were observed, while citrate, trimethylamine (TMA) and dimethylamine were increased. These changes suggest that depression may be associated with gut microbes, energy metabolism and glycometabolism. Genipin showed the best anti-depressive effects at a dose of 100 mg/kg in rats. These results indicate that metabonomic approaches could be powerful tools for the investigation of the biochemical changes in pathological conditions or drug treatment.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Structure of Genipin.
Figure 2
Figure 2. Effect of genipin treatment on the body weight (a), sucrose preference (b), crossing numbers (c), and rearing numbers (d) in CUMS exposed rats (NS: control group not receiving CUMS, MS: CUMS and vehicle, YV: CUMS plus Venlafaxine, GH: CUMS plus genipin high dose, GM: CUMS plus genipin middle dose, GL: CUMS plus genipin low dose).
Values given are the mean±SEM (n = 10). **p<0.01, *p<0.05 as compared with the model.
Figure 3
Figure 3. Typical 600 MHz 1H-NMR standard spectra of serum and urine collected from NS (a) and MS (b) group rats.
A total of 35 metabolites were unambiguously assigned, their chemical shifts and peak multiplicities are given in Table 1.
Figure 4
Figure 4. PCA score plots (a, c) and corresponding loading plots (b, d) based on 1H-NMR spectra of serum (a, b) and urine (c, d) between NS and MS groups.
Figure 5
Figure 5. PCA score plots based 1H-NMR spectra of serum (a) and urine (b) samples from NS, MS, YV, GH, GM and GL groups.
Figure 6
Figure 6. PCA score plots (a, c, e, and g) and corresponding loading plots (b, d, f and h) based on 1H-NMR spectra of serum samples between MS group and other treatment groups including YV, GH, GM and GL groups, respectively.
Figure 7
Figure 7. PCA score plots (a, c, e, and g) and corresponding loading plots (b, d, f and h) based on 1H-NMR spectra of urine samples between MS group and other treatment groups including YV, GH, GM and GL groups, respectively.
Figure 8
Figure 8. An overview of the metabolic pathways related to the CUMS-induced depression.
The ↑ or ↓ was a demonstration of increased or decreased metabolites in serum and urine as compared with the control rats.
See this image and copyright information in PMC

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