ABSTRACT
A UPLC-Q-Orbitrap-MS based metabolomic approach combined with biochemical assay and histopathological inspection were employed to study the intervention effects of Suanzaoren Decoction (SZRD) on chronic unpredictable mild stress (CUMS) depression rats, and to clarify the metabolic regulation pathway of SZRD. The rats were randomly divided into normal control group, CUMS model group, positive drug venlafaxine group, SZRD high (24 g·kg-1) and low (12 g·kg-1) dose groups, respectively. The CUMS model was replicated by subjecting to a variety of stimulus, such as thermal stimulation, ice water swimming, ultrasonic stimulation, tail clamping, day and night reversal, plantar electric shock and so on for rats. After oral administration of drugs for 28 days, the behavioral indexes of rats in each group were observed and the hippocampus and serum samples of rats were collected for biochemical assay and histopathological inspection. Compared with the CUMS model group, low dose and high dose SZRD groups can significantly reduce the immobility time of forced swimming (P < 0.001, P < 0.001), increase the sucrose preference rate (P < 0.01, P < 0.05), the number of crossings (P < 0.05, P < 0.01) and the number of uprights (P < 0.05, P < 0.01) in the open field test, suggesting that SZRD can significantly improve the depression-like behavior of CUMS model rats. In addition, SZRD could significantly reduce the levels of serum IL-6, IL-1β and TNF-α of CUMS model rats. A total of 21 differential metabolites in serum were identified by comparison with the data from the literature and databases. In addition, low-dose SZRD and high-dose SZRD improved the 8 and 11 perturbed potential serum biomarkers that were induced by CUMS, respectively, which related to alanine, aspartic acid and glutamic acid, tryptophan and arachidonic acid metabolism. This study provides a scientific basis for expanding the clinical indications of SZRD. This experiment was approved by the Animal Ethics Committee of Shanxi University (Approval No. SXULL2020028).
ABSTRACT
The purpose of this study was to systematically analyze the antidepressant mechanism of Chaigui granules from the perspective of biological metabolic network by using integrated metabolomics and biological network analysis tools. The model of chronic unpredictable mild stress (CUMS) depression rat was established, and LC-MS-based plasma metabolomics was used to identify the key metabolites and analyze metabolic pathways underlying the antidepressant effects of Chaigui Granules. The key metabolites regulated by Chaigui granules was integrated with biological network analysis tools to further focus on the key metabolic pathways and explore the potential targets of the antidepressant effect of Chaigui granules. The results showed that there were significant differences in the plasma levels of 20 metabolites in the model group compared with the control group (P < 0.05), Chaigui granules significantly regulated 12 metabolites including docosatrienoic acid, 3-hydroxybutyric acid, 4-hydroxybenzaldehyde, chenodeoxycholic acid, cholic acid, L-glutamine, glycocholic acid, linoleyl carnitine, L-tyrosine, N-acetylvaline, palmitoylcarnitine, arachidonic acid. Further network analysis of the key metabolites regulated by Chaigui granules indicated that plasma arachidonic acid metabolism might be the core pathway for the antidepressant effect of Chaigui granules, with 10 proteins were potential targets for the antidepressant effect of Chaigui granules, including CYP2B6, CYP2E1, CYP2C9, CYP2C8, PLA2G6, PTGS2, ALOX15B, PTGS1, ALOX12 and ALOX5. The animal experimental operations involved in this paper was followed the regulations of the Animal Ethics Committee of Shanxi University and passed the animal experimental ethical review (Approval No. SXULL2020028).
ABSTRACT
Objective: To study the mechanism of Jiaotai Pill on inflammation and anti-inflammatory cytokines in mice with chronic unpredictable mild stress (CUMS) depression. Methods: Mice were treated with CUMS depression model, then the weight comparison, sugar test, opening experiment was conducted; The levels of IL-1β, IL-6 and TNF-α, IL-4, and IL-10 in the serum and hippocampus of rats were measured by enzyme-linked immunosorbent assay (ELISA), and rat hippocampal neuron morphology was observed by Nissl's staining. Results: Compared with the blank group, the consumption of sugar, the number of crosses and the number of vertical bars in the model group were significantly decreased; The levels of IL-1β, IL-6, TNF-α, and IL-4 in serum and hippocampus were significantly higher than those in the blank group, and IL-10 significantly reduced; Hippocampal neurons stratified unclear, arranged disorder, Nissie shallow staining or disappear. Compared with the model group, the consumption of sugar, the number of crosses and the number of vertical bars in Jiaotai Pill administration group were significantly increased; The levels of IL-1β, IL-6, and TNF-α in serum and hippocampus were significantly decreased, and the levels of IL-4 and IL-10 was significantly increased; Hippocampal neuronal stratification was more obvious, Nissl shallow staining. Conclusion: Jiaotai Pill can significantly improve the behavior of rat depression and hippocampal neuronal injury whose mechanism may be related to down-regulation of serum and hippocampus proinflammatory cytokines IL-1β, IL-6, TNF-α, up-regulation of anti-inflammatory cytokines IL-4 and IL-10.
ABSTRACT
Objective: To validate the antidepressant effect of herb pair of Bupleuri Radix and Paeoniae Alba Radix by observing its interference effect in the chronic unpredictable mild stress (CUMS) depression model of rats. Methods: After the interference of herb pair of Bupleuri Radix and Paeoniae Alba Radix in CUMS depression model of rats, those changes of rat body weight, sugar water consumption, and the opening activity behavior were observed. Results: After the interference of herb pair of Bupleuri Radix and Paeoniae Alba Radix in CUMS depression model of rats for two weeks, the test indexes of rat body weight, sugar water consumption, and the opening activity behavior were significantly increased in low-, mid-, and high-dose herb pair of Bupleuri Radix and Paeoniae Alba Radix groups. The effect of herb pair of Bupleuri Radix and Paeoniae Alba Radix on improving the behavior of rats with depression was proved. In addition, Bupleuri Radix and Paeoniae Alba Radix could also improve the level of individual indicators in a certain degree. Conclusion: Herb pair of Bupleuri Radix and Paeoniae Alba Radix has the obvious antidepressant effect on rats and the antidepressant effect of Bupleuri Radix and Paeoniae Alba Radix separately is lower than it.