Based on serum metabolomics and gut microbiota technology, this study explores the effects and mechanisms of the water extract of Ziziphi Spinosae Semen(SZRW) and the petroleum ether extract of Ziziphi Spinosae Semen(SZRO) in improving depressive-like behaviors induced by sleep deprivation. A modified multi-platform water environment method was employed to establish a rat model of sleep deprivation. Depressive-like behaviors in rats were assessed through the sucrose preference test and forced swim test. The expression of barrier proteins, such as Occludin, in the colon was determined by immunofluorescence. UPLC-Q-Orbitrap MS was utilized to analyze the serum metabolic profiles of sleep-deprived rats, screen for differential metabolites, and analyze metabolic pathways. The diversity of the gut microbiota was detected using 16S rRNA gene sequencing. Spearman correlation coefficient analysis was conducted to assess the correlation between differential metabolites and gut microbiota. The results indicated that SZRO significantly increased the sucrose preference index and decreased the immobility time in the forced swim test in rats. A total of 34 differential metabolites were identified through serum metabolomics. SZRW and SZRO shared five metabolic pathways, including phenylalanine metabolism. SZRW uniquely featured taurine and hypotaurine metabolism, while SZRO uniquely featured linoleic acid metabolism and tyrosine metabolism. Correlation analysis revealed that SZRW could upregulate the abundance of Bilophila, promoting the production of indole-3-propionic acid and subsequently upregulating the expression levels of intestinal tight junction proteins such as ZO-1, Occludin, and Claudin-1. SZRO could indirectly influence metabolic pathways such as arginine metabolism and linoleic acid metabolism by upregulating the abundance of gut microbiota such as Coprococcus and Eubacterium species. Both SZRW and SZRO can regulate endogenous metabolism, including amino acids, energy, and lipids, alter the gut microbiota microecology, and improve depressive-like behaviors. SZRO demonstrated superior effects in regulating metabolic pathways and gut microbiota structure compared to SZRW. The findings of this study provide a scientific basis for elucidating the pharmacodynamic material basis of Ziziphi Spinosae Semen.
Animals ; Rats ; Gastrointestinal Microbiome/drug effects* ; Male ; Metabolomics ; Drugs, Chinese Herbal/administration & dosage* ; Depression/blood* ; Rats, Sprague-Dawley ; Sleep Deprivation/complications* ; Ziziphus/chemistry* ; Antidepressive Agents/administration & dosage* ; Behavior, Animal/drug effects* ; Humans

Depression is an important post-stroke sequela with negative impact on mortality, functional outcome and quality of life. Changes in cytokines have been hypothesized to be associated with the etiology of post-stroke depression (PSD). The altere dhypothalamic-pituitary-adrenal (HPA) functioning is associated with the onset of depression. The activity of HPA could induce the fluctuations of cortisol levels. In this study, we prospectively checked interleukin 6 (IL-6) and cortisol levels in patients with early ischemic stroke. It was hypothesized that early serum IL-6 and cortisol fluctuations in stroke patients were the predictions of PSD. Totally, 100 participants were selected from stroke inpatients consecutively admitted to the Department of Neurology, Tongji Hospital from July 2014 to December 2015. Fifty health people served as the controls. The serum of all the patients was collected at 8:00 am and 4:00 pm respectively one week after stroke. The serum of controls was collected only at 8:00 am. The levels of IL-6 were analyzed by enzyme-linked immunosorbent assay kit, and those of cortisol were detected by chemiluminescence immunoassay. On the 3rd week after stroke, the patients were enrolled to the PSD group and non-PSD group based on the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) and The Hamilton Depression Rating Scale (HAMD-21, score>7). The IL-6 level (13.24±2.89 ng/L) was elevated significantly in PSD groups as compared with that in non-PSD group and control group respectively (P<0.05 for both), but there was no significant difference in the IL-6 level between non-PSD group and control group. The patients in both PSD group and non-PSD group had significantly elevated morning cortisol levels in comparison with those in the control group (P<0.05; for PSD, non-PSD and control: 508.86±119.51, 420.83±70.04 and 340.40±76.30 nmol/L respectively). Moreover, afternoon cortisol levels in PSD group were significantly higher than those in non-PSD group, and the morning baseline cortisol levels in these two groups were similar (P>0.05). It was suggested that PSD generally runs a chronic course and is related to a variety of adverse health outcomes including increased disability, morbidity and mortality. This study will help the screening of potential PSD in the early stage.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Depression ; blood ; etiology ; physiopathology ; Female ; Humans ; Hydrocortisone ; blood ; Hypothalamo-Hypophyseal System ; metabolism ; Interleukin-6 ; blood ; Male ; Middle Aged ; Stroke ; blood ; complications ; physiopathology

OBJECTIVETo study the effect of Modified Guipi Decoction (MGD) on blood pressure and quality of life (QOL) in hypertension patients complicated depression.

METHODSTotally 245 hypertension patients complicated depression were randomly assigned to the treatment group (125 cases, treated with MGD) and the control group (120 cases, treated with Sertraline). Final recruited qualified patients were 117 cases in the treatment group and 111 cases in the control group. The therapeutic course for all was 4 weeks. Changes of blood pressure, scores rated by Hamilton Depression Scale-17 (HAMD-17), Hamilton Anxiety Rating Scale (HAMA), short-form 36 health survey questionnaire (SF-36), and Treatment Emergent Symptom Scale (TESS) were observed before and after treatment, thereby judging their efficacies.

RESULTS(1) Compared with before treatment in the same group, systolic and diastolic blood pressures significantly decreased in the treatment group after 2 weeks of treatment; systolic blood pressure significantly-decreased after 2 weeks of treatment and diastolic blood pressure significantly decreased after 3 weeks of treatment in the control group (all P < 0.05, P < 0.01). Decreased valley values of systolic and diastolic blood pressures at week 2, 3, and 4 after treatment were obviously higher than those at week 1 after treatment in the two groups (P < 0.05, P < 0.01). Compared with the control group at week 4 after treatment, valley value of systolic blood pressure obviously decreased in the treatment group (P <0. 01). Decreased valley values of systolic and diastolic blood pressures in the treatment group were higher than those of the control group (P <0. 01). The success rate of target blood pressure was 60. 7% (71/117 cases) in the treatment group and 42. 3% (47/111 cases) in the control group, with statistical difference (χ² = 7.6781, P < 0.01). (2) Compared with before treatment in the same group, the score of HAMD-17 at week 2, 3, and 4 after treatment all decreased in the two groups (P < 0.01). Compared with the control group, the score of HAMD-17 at week 4 after treatment decreased more obviously in the treatment group, with higher difference in decreased value (P < 0.05). The effective rate was 79.5% (93/117) in the treatment group, higher than that in the control group [66.7% (74/111); χ² = 4.7741, P < 0.05]. (3) Compared with before treatment in the same group, the score of HAMA at week 1, 2, 3, and 4 after treatment all obviously decreased in the two groups (P <0. 05, P <0. 01). Compared with the control group, the score of HAMA at week 3 and 4 after treatment decreased more obviously in the treatment group, with higher difference in decreased value (P < 0.05, P < 0.01). (4) After 4 weeks of treatment, except physical function in the control group, SF-36 total score and the score for each factor were obviously higher in the two groups (P < 0.05, P < 0.01). MGD showed superior effect in improving physical function, physical activity, overall health, emotion activity, and health changes to that of Sertraline (P < 0.05, P < 0.01). (5) The incidence of insomnia, tremor, liability to agitation, dizziness was obviously less in the treatment group than in the control group (P < 0.05).

CONCLUSIONSMGD had favorable clinical effect on hypertension patients complicated depression. Meanwhile, it also could improve their blood pressure and QOL.

Antidepressive Agents ; therapeutic use ; Blood Pressure ; drug effects ; Depression ; drug therapy ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; Hypertension ; complications ; Phytotherapy ; Psychiatric Status Rating Scales ; Quality of Life ; Sertraline ; therapeutic use ; Surveys and Questionnaires

OBJECTIVETo investigate the relationship between atopic allergy and depression and the role of DBP in the development of depression.

METHODSBALB/c mice were randomly divided into eight groups: saline; ovalbumin (OVA)-immunized; saline+DBP (0.45 mg/kg•d); saline+DBP (45 mg/kg•d); DBP (0.45 mg/kg•d) OVA-immunized; DBP (45 mg/kg•d) OVA-immunized; saline+hydrocortisone (30 mg/kg•d); and hydrocortisone (30 mg/kg•d)-exposed OVA-immunized. Behavior (e.g. open-field, tail suspension, and forced swimming tests), viscera coefficients (brain and spleen), oxidative damage [e.g. reactive oxygen species (ROS), malondialdehyde (MDA), and glutathione (GSH)], as well as levels of IgE and IL-4, were then analyzed.

RESULTSIn the saline and OVA groups, the degree of depression symptoms in mice increased with increasing DBP concentration. Additionally, the OVA-immunity groups were associated with more serious depressive behavior compared with the same exposure concentration in the saline group. Oxidative damage was associated with a dose-dependent increase in DBP in the different groups. IL-4 and IgE levels were associated with low-dose DBP stimulation, which changed to high-dose inhibition with increasing DBP exposure, possibly due to spleen injury seen at high DBP concentrations.

CONCLUSIONDevelopment of an atopic allergy has the potential to increase the risk of depression in mice, and it seems that DBP helps OVA to exert its effect in our present model. Moreover, the results of our study implicate a certain connection between brain oxidative stress and depression, which deserves a further exploration.

Animals ; Behavior, Animal ; drug effects ; Body Weight ; Depression ; blood ; chemically induced ; immunology ; Dibutyl Phthalate ; immunology ; toxicity ; Environmental Pollutants ; immunology ; toxicity ; Hydrocortisone ; Hypersensitivity, Immediate ; blood ; complications ; Immunization ; Immunoglobulin E ; blood ; Interleukin-4 ; blood ; Male ; Mice ; Mice, Inbred BALB C ; Ovalbumin ; Oxidative Stress

OBJECTIVETo observe the effect of hesperidin on behavior and hypothalamic-pituitary-adrenal (HPA) axis of ratmodel of chronic stress-induced depression.

METHODChronic unpredictable mild stress (CUMS) was used to establish the rat depression model. Sixty male SD rats were divided randomly into six groups: the normal group, the model group, the hesperidin (40, 80, 160 mg x kg(-1)) group and the positive fluoxetine (10 mg x kg(-1)) group. They were orally administered with drugs for three weeks. The sucrose preference test and the forced swimming test (FST) were assayed to detect animal behavior. The levels of corticosterone (CORT) in serum, mRNA of corticotropin release factor (CRF) in hypothalamus as well as protein expression of glucocorticoid receptor (GR) in paraventricular nucleus (PVN) were determined to clarify the anti-depression effect and mechanism of hesperidin.

RESULTCompared with the model group, rats in the hesperidin (40, 80, 160 mg x kg(-1)) treatment group showed significant increase in the sucrose consumption and decrease in the immobility time in FST to varying degrees. Meanwhile, the excessively high serum CORT and adrenal index of CUMS rats were reversed by treatment with hesperidin. In addition, hesperidin inhibited CRF mRNA expression in hypothalamus and up-regulated GR protein expression in PVN among CUMS rats.

CONCLUSIONHesperidin could effectively improve the behavior of CUMS rats and show the anti-depression effect. Its mechanisms may be related to the function of regulating HPA axis.

Administration, Oral ; Animals ; Behavior, Animal ; drug effects ; Corticosterone ; blood ; Corticotropin-Releasing Hormone ; genetics ; metabolism ; Depression ; drug therapy ; etiology ; Fluoxetine ; administration & dosage ; Gene Expression Regulation ; drug effects ; Hesperidin ; administration & dosage ; pharmacology ; Hypothalamo-Hypophyseal System ; drug effects ; physiopathology ; Hypothalamus ; metabolism ; Male ; Models, Animal ; Pituitary-Adrenal System ; drug effects ; physiopathology ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Receptors, Glucocorticoid ; metabolism ; Stress, Psychological ; complications ; drug therapy ; Sucrose ; metabolism ; Swimming ; Up-Regulation

This study is to investigate the amelioration effect of glucocorticoid receptor (GR) antagonist mifepristone on the changes of learning and memory abilities in rat model of depression. In the present study, a 35-day rat chronic unpredictable stress (CUS) model was used to observe both depression-like behaviors with sucrose preference test and open-field test and learning and memory-associated behaviors with Morris water maze test. A total of 45 male adult Sprague-Dawley rats were randomly assigned to three groups of equal size: control group (CON); CUS group (CUS); CUS + mifepristone group (CM). Animals in CM group were first exposed to CUS for 14 days, and then were administered with 50 mg x kg(-1) x d(-1) of mifepristone with continued CUS procedure. Corticosterone EIA Kit was used to detect the concentration of plasma corticosterone (CORT). Nissl staining was used to observe the structure of hippocampus. The results demonstrated that CUS exposure induced both depressive-like and learning and memory-associated behaviors and these deficits were reversed by mifepristone. Compared to CON group, the concentration of plasma CORT increased significantly in CUS group. CUS exposure damaged the structure of hippocampus, whereas mifepristone had an amelioration effect. Together, the structural deficits of hippocampus resulting from long-term stress exposure, which could contribute to the impairment of learning and memory in depression, are reversed by the GR receptor antagonist mifepristone.
Animals ; Behavior, Animal ; drug effects ; Corticosterone ; blood ; Depression ; blood ; etiology ; pathology ; physiopathology ; Hippocampus ; pathology ; Learning ; drug effects ; Male ; Memory ; drug effects ; Mifepristone ; pharmacology ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Receptors, Glucocorticoid ; antagonists & inhibitors ; Stress, Psychological ; complications

OBJECTIVE: To investigate the change of serum myeloperoxidase (MPO) and lipoxin A4 (LXA4) in coronary heart disease (CHD) patients with anxiety and depression and its clinical significance. METHODS: From December 2010 to February 2011, 143 CHD patients and 44 non-CHD patients (the control group) hospitalized in the Department of Cardiology at the Second Xiangya Hospital were enrolled. The hospital anxiety and depression scale (HADS) was used to evaluate the psychological state of all patients and the CHD patients were assigned to an anxiety and depression group (n=57) or a non-depression and anxiety group (n=86). The serum levels of high sensitive C-reactive protein (Hs-CRP), MPO, and LXA4 were examined, and the ratio of MPO and LXA4 (M/L) was calculated. RESULTS: The levels of Hs-CRP, MPO, and LXA4 as well as M/L ratios in both CHD groups were significantly higher than those in the control group (all P<0.01). Compared with the non-anxiety and depression group, the levels of MPO and LXA4, and M/L ratios in the anxiety and depression group increased (all P<0.05). Correlation analysis showed that MPO was positively correlated with the score of HADS-total (HADS-t), HADS-anxiety (HADS-a), or HADS-depression (HADS-d), while LXA4 was negatively correlated with HADS-t or HADS-d. Multiple ordinal logistic regression analysis revealed that higher HADS-t score, stable angina, unstable angina, and acute myocardial infarction were the independent impact factors for the elevation of M/L ratio. CONCLUSION Anxiety and depression may aggravate the inflammatory response in CHD patients. The imbalance between inflammation and anti-inflammation may be part of the mechanism.
Aged ; Anxiety ; complications ; Case-Control Studies ; Coronary Disease ; blood ; complications ; Depression ; complications ; Female ; Humans ; Inflammation ; Lipoxins ; blood ; Male ; Middle Aged ; Peroxidase ; blood

OBJECTIVE: To investigate the effect of antidepressant and psychological intervention on the blood pressure and quality of life in hypertensive patients with depression. METHODS: After evaluating 950 patients with essential hypertension by Hospital Anxiety and Depression Scale (HAD), patients with HAD positive results were evaluated with Hamilton Depression Scale (HAMD) and Hamilton Anxiety Scale (HAMA). The positive subjects with HAMD were randomly divided into an antidepressant and psychological intervention group (n=30, including routine treatment, mental state intervention, and antidepressant treatment) and a control group (n=30, routine treatment alone). The blood pressure, quality of life, and level of depression were compared between the 2 groups. RESULTS: The depression symptoms were significantly improved in the antidepressant and psychological intervention group. The HAMD score fell from 30.03+/-1.83 at entrance to 17.43+/-1.96 at the end of study. The blood pressure control was more effective in the antidepressant and psychological intervention group than in the control group. The mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) decreased by 26.17 mmHg and 13.63 mmHg in the antidepressant and psychological intervention group, while there were only 14.32 mmHg and 7.18 mmHg decrease in SBP and DBP respectively in the control group. Patients in the antidepressant and psychological intervention group had a higher score in the quality of life. The total score of GQOLI-74 increased from 65.97+/-4.68 before the treatment to 71.20+/-5.13 after the treatment. CONCLUSION Psychological intervention and antidepressant can improve the blood pressure control and quality of life in hypertensive patients with depression.
Adult ; Antidepressive Agents ; therapeutic use ; Blood Pressure ; drug effects ; Depression ; complications ; therapy ; Female ; Humans ; Hypertension ; complications ; drug therapy ; psychology ; Male ; Middle Aged ; Psychotherapy ; Quality of Life

Adult ; Antihypertensive Agents ; therapeutic use ; Blood Pressure ; drug effects ; Depression ; complications ; drug therapy ; physiopathology ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Hypertension ; complications ; drug therapy ; physiopathology ; Male ; Middle Aged ; Phytotherapy ; Powders ; Treatment Outcome

OBJECTIVETo observe clinical therapeutic effect of head point-through-point electroacupuncture (EA) on poststroke depression (PSD) and to study the mechanism.

METHODSOne hundred and eight cases of PSD were randomly divided into a point-through-point EA group (n = 38), a non point-through-point group (n = 36) and a western medicine group (n = 34). After treatment of 28 days, their therapeutic effects, scores of HAMD depression scale and SDS self-rating scale, and plasma 5-HT contents were compared before and after treatment among the 3 groups.

RESULTSThe effective rate of 86.84% in the point-through-point EA group was better than 63.89% in the non point-through-point group and 67.65% in the western medicine group (P < 0.05 or P < 0.01). Plasma 5-HT content in the point-through-point EA group increased significantly, with a very significant difference as compared with that of the non point-through-point group (P < 0.01).

CONCLUSIONHead point-through-point therapy can obviously increase plasma 5-HT content of the patient with PSD, so as to cure poststroke depression, with a better therapeutic effect than other two groups.

Adult ; Aged ; Depression ; therapy ; Electroacupuncture ; Female ; Humans ; Male ; Middle Aged ; Scalp ; Serotonin ; blood ; Stroke ; complications