Браузер не даёт сохранять данные (например, приватный режим): закладки пропадут после закрытия вкладки.
Поиск статей PubMed
Ключевые слова, автор, журнал, годы — результаты из PubMed, аннотации с переводом на русский, закладки в браузере.
Найдено: 3 203
Страница 124 из 321-
A Polysaccharide-Rich Ingredient from Hypericum perforatum L. Ameliorates Depression-like and Post-Traumatic Stress Disorder-like Symptoms in Mouse Models.
Background/Objectives: Hypericum perforatum L. (H. perforatum), commonly known as St. John's wort, has been widely used in clinical practice to treat mental disorders. Previous studies and clinical applications have primarily focused on its alcohol-soluble ingredients. Our research was designed to investigate the physicochemical properties, antidepressant-like effects, and anti-post-traumatic stress disorder (PTSD)-like effects of the alcohol-insoluble polysaccharide-rich ingredients from H. perforatum. Meanwhile, the underlying mechanisms were elucidated. Methods: The physicochemical properties of two polysaccharide-rich ingredients, designated as HPP1 and HPP2, were characterized using colorimetric assay, capillary electrophoresis, high-performance gel permeation chromatography, and fourier transform infrared spectroscopy. Behavioral despair tests were conducted to rapidly assess and compare their antidepressant-like effects in mice. Subsequently, behavioral despair mice and foot-shock mice were established to thoroughly explore the impact of HPP2 on depression-like and PTSD-like symptoms. The effects of HPP2 on cerebral pathological changes, neurotrophic factors, and gut microbiota in foot-shock mice were detected through hematoxylin & eosin staining, immunofluorescence staining, and 16S rDNA (V3 + V4 regions) gene sequencing. Results: HPP1 and HPP2 are predominantly composed of arabinose, glucose, galactose, mannose, and galacturonic acid. The molecular weight distribution of HPP1 ranges from 1133 to 67,278 Da, whereas that of HPP2 extends from 1493 to 38,407 Da. Acute pre-treatment with HPP1 or HPP2 (200 mg/kg, i.g.) could reduce mice's immobility in behavioral despair tests, with HPP2 exhibiting superior efficacy. Additionally, both acute and sub-chronic pre-treatment with HPP2 (50, 200, and 800 mg/kg, i.g.) effectively alleviated depression-like symptoms in behavioral despair mice. Prolonged pre-treatment with HPP2 (200 mg/kg, i.g.) also mitigated the slow increase in body weight and behavioral abnormalities in foot-shock mice. Furthermore, HPP2 (200 mg/kg) successfully restored hippocampal histomorphological abnormalities, neurotrophic disturbance, and dysregulation of the gut microbiota in foot-shock mice. Conclusions: HPP2 exerts noteworthy antidepressant-like and anti-PTSD-like impact in mouse models via multiple targets, indicating a potential therapeutic candidate in depression and PTSD therapy.
-
Integration of network pharmacology and untargeted metabolomics reveals Changpu San's antidepressant mechanisms via tryptophan metabolism.
ETHNOPHARMACOLOGICAL RELEVANCE: Changpu San (CPS) is a traditional Chinese medicine (TCM) formula historically used to treat symptoms resembling depression. However, its antidepressant effects and underlying mechanisms remain unclear. AIM OF THE STUDY: This study aims to evaluate CPS's antidepressant effects and elucidate its mechanisms by combining network pharmacology with untargeted metabolomics. MATERIALS AND METHODS: A chronic unpredictable mild stress (CUMS) mouse model was used to assess CPS's antidepressant effects via behavioral tests and body weight monitoring. By integrating network pharmacology and untargeted metabolomics, both based on UPLC-Q-Exactive-Orbitrap-MS for CPS chemical profiling and serum metabolite analysis, a key pathway was identified. This pathway was validated through UPLC-QQQ-MS/MS and ELISA by measuring relevant biomarkers, while its association with colonic microbiota was further investigated using 16S rDNA sequencing. RESULTS: CPS alleviated depression-like behaviors in CUMS mice. A total of 140 compounds were identified in CPS, revealing 140 core targets related to depression. Metabolomics analysis identified 42 serum metabolites significantly altered in CUMS mice, with tryptophan metabolism emerging as a shared pathway across both approaches. Experimental validation showed CPS partially reversed tryptophan metabolism dysregulation, significantly increasing tryptophan levels and reducing kynurenine levels in the brain. Moreover, CPS modulated the colonic microbiota, with key genera such as Prevotella and Bacillus showing correlations with tryptophan metabolism and inflammation. CONCLUSION: CPS shows promise as an effective antidepressant, potentially through modulating tryptophan metabolism and reshaping colonic microbiota. This study provides valuable insights into its mechanisms and offers a methodological reference for researching other TCM formulas.
-
Probiotics and Subclinical Psychological Symptoms in Healthy Participants: A Systematic Review and Meta-Analysis.
INTRODUCTION/AIM: Interest in the gut-brain axis and emerging evidence that the intestinal microbiota can influence central nervous system function has led to the hypothesis that probiotic supplementation can have a positive effect on mood and psychological symptoms such as depression and anxiety. Although several human clinical trials have investigated this, results have been inconsistent. Therefore, a systematic review and meta-analytic approach was chosen to examine if probiotic consumption has an effect on psychological symptoms. METHODS: The online databases PubMed, Scopus, and the Cochrane Library were searched for relevant studies up to July 2016. Those that were randomized and placebo controlled and measured preclinical psychological symptoms of depression, anxiety, and perceived stress in healthy volunteers pre and post supplementation with a probiotic were included. To control for differences in scales of measurement, data were converted to percentage change, and the standardized mean difference between the probiotic and control groups was investigated using Revman software. A random effects model was used for analysis. Heterogeneity was assessed using the I2 statistic. Quality assessment was undertaken using the Rosendal scale. RESULTS: Seven studies met the inclusion criteria and provided data for nine comparisons. All studies passed the quality analysis. The meta-analysis showed that supplementation with probiotics resulted in a statistically significant improvement in psychological symptoms (standardized mean difference 0.34; 95% confidence interval 0.07-0.61, Z = 2.49) compared with placebo. CONCLUSION: These results show that probiotic consumption may have a positive effect on psychological symptoms of depression, anxiety, and perceived stress in healthy human volunteers.
-
Quercetin inhibits neuronal Ferroptosis and promotes immune response by targeting lipid metabolism-related gene PTGS2 to alleviate breast cancer-related depression.
BACKGROUND: Quercetin, the key ingredient in Xiaoyao Kangai Jieyu Formula, has been previously found to relieve breast cancer-related depression (BCRD). PURPOSE: We want to explore the potential mechanisms and therapeutic targets of quercetin alleviating BCRD. METHODS: BALB/c mice were injected subcutaneously with 4T1 cells and corticosterone (CORT) to create a BCRD mice model. The primary hippocampal neurons were co-induced with 10 μg/ml lipopolysaccharide (LPS) and 200 μM CORT for 6 h to establish an in vitro model of BCRD. Quercetin was applied to explore its effect on disease symptoms, gut microbiota, and lipid metabolism of BCRD mice. Lipid metabolism-related genes were screened based on network pharmacology. Molecular docking was employed to prove whether quercetin bound to prostaglandin-endoperoxide synthase 2 (PTGS2). PTGS2 overexpression was carried out to explore the underlying mechanism of quercetin treatment on BCRD. RESULTS: Quercetin treatment not only altered the composition and abundance of gut microbiota but also alleviated abnormal lipid metabolism in BCRD mice. In particular, quercetin down-regulated BCRD and lipid metabolism-related genes screened by network pharmacology, especially PTGS2. Further, molecular docking verified the stable binding between quercetin and PTGS2. In hippocampal neurons, quercetin promoted proliferation but reduced ferroptosis-related markers (total Fe, Fe2+, MDA, and ROS) levels by targeting PTGS2. In BCRD mice, quercetin reduced the high immobility time and increased the sucrose preference rate and serotonin (5-HT), dopamine (DA), and noradrenaline (NE) levels. Meanwhile, quercetin increased CD4+/CD8+ T cells ratio and IL-2 and IFN-γ levels but reduced CA153 and IL-10 levels to alleviate BCRD development. However, PTGS2 overexpression reversed these effects of quercetin on BCRD. CONCLUSION: Quercetin inhibited neuronal ferroptosis and promoted immune responses in BCRD mice by targeting the lipid metabolism-related gene PTGS2. This provided a reference for quercetin in the treatment of BCRD.
-
The Effect of Prebiotics and Probiotics on Levels of Depression, Anxiety, and Cognitive Function: A Meta-Analysis of Randomized Clinical Trials.
INTRODUCTION: Recent studies have emphasized the relationship between mental health and the human intestine microbiota. In this study, we evaluate the effect of consuming Biotics, on levels of depression, anxiety, and cognitive function. METHODS: This meta-analysis adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards. We searched MEDLINE (PubMed), Cochrane Library, Scopus, Web of Science, and ClinicalTrials.gov. All full-text articles and major reviews were manually searched for additional studies. RESULTS: The initial analysis was based on the concept that consuming Biotics causes changes in anxiety, measured using various instruments. This analysis showed that consuming Biotics significantly reduced anxiety in our study participants (SMD = 0.2894, Z = 2.46, P = 0.0139, I^2 = 92.4%). The meta-analysis included 4295 samples (2194 in the experimental group and 2101 in the control group). In terms of depression, the analysis showed that consuming Biotics significantly reduced depression in our study participants (SMD = 0.2942, Z = 2.13, P = 0.0335, I^2 = 91.7%). The meta-analysis included 3179 samples (1603 in the experimental group and 1576 in the control group). Regarding cognitive function, the analysis showed that consuming Biotics significantly improved cognitive function in our study participants (SMD = 0.4819, Z = 3.00, P = 0.0027, I^2 = 77.9%). The meta-analysis included 915 samples (470 in the experimental group and 445 in the control group). CONCLUSIONS: Our results indicate that most recent studies support the effectiveness of probiotics in reducing symptoms of anxiety, depression, and cognitive issues despite some discrepancies in the findings. People with mild symptoms may experience greater benefits from taking probiotics. TRIAL REGISTRATION: PROSPERO registration ID: CRD42024589507.
-
Almonds and Their Impact on Mental Health and the Gut-Brain Axis in Adults with Symptoms of Anxiety and Depression: A 12-Week Randomized Controlled Trial.
BACKGROUND: Almonds contain dietary fiber, micronutrients, and phytochemicals that have been implicated in the regulation of the gut-brain axis and mental health. OBJECTIVES: The aim of this study was to investigate the effect of whole almonds, compared with an isocaloric snack, on mental health and the gut-brain axis, in adults with symptoms of anxiety and depression. METHODS: Adults with mild-to-moderate symptoms of anxiety and depression participated in a randomized controlled trial, receiving almonds (56 g/d) or isocaloric control for 12 wk. The primary outcome was symptoms of anxiety and depression (Patient Health Questionnaire Anxiety and Depression Scale) at week 12. Secondary mental health outcomes were measured at weeks 0, 6, and 12. Gut microbiota composition (16S rRNA gene sequencing), short-chain fatty acids (SCFAs; gas chromatography), stool output (frequency and consistency), and gut symptoms (7-d diary) were measured at weeks 0 and 12. RESULTS: Eighty-four participants were recruited (mean age 25 y, 75% female). There was no significant difference in anxiety and depression scores between the almond (mean ± SD, 11.6 ± 5.3) and control group (12.5 ± 5.3; P = 0.945). Functional impairment was borderline significantly improved in the almond group (9.6 ± 7.0) compared with control (12.2 ± 8.7, P = 0.055) in the intention-to-treat analysis and was significant in the per-protocol analysis (almond 9.0 ± 6.4 compared with control 12.5 ± 9.6; P = 0.015). Almonds did not alter the gut microbiota composition or SCFA concentrations. Almonds significantly reduced the frequency of hard stools compared with control (median [interquartile range]: 0.0 [0.1] compared with 0.1 [0.4] stools/d, P = 0.002), with no impact on gut symptoms. CONCLUSIONS: Almond consumption for 12 wk has limited impact on anxiety and depression, although it may impact functional impairment in adults with mild-to-moderate anxiety and depression. Further research is needed in populations with severe depression and anxiety. This trial was registered at clinicaltrials.gov as NCT06087471.
-
Desulfovibrio vulgaris trigger depression-like behavior in mice through dual disruption of colonic homeostasis and fatty acid metabolism.
OBJECTIVE: Desulfovibrio is a genus of sulfate-reducing bacteria residing in the gut, and growing evidence has implicated it in the pathogenesis of depression. However, the exact association and intrinsic mechanisms between the two remain unelucidated. This study aims to investigate whether Desulfovibrio induces depression-like behaviors in mice via the Microbiota-Gut-Brain Axis and to preliminarily elucidate the underlying mechanisms. METHODS: A two-week Desulfovibrio-induced mouse model of depression was established in this study. Based on preliminary experimental results, a Desulfovibrio bacterial suspension concentration of 1 × 10^8 CFU/ml, which demonstrated a more pronounced impact on depression-like behaviors in mice, was selected to investigate the intervention effect of Desulfovibrio on depression and its underlying mechanisms. Behavioral changes in mice were assessed using the sucrose preference test (SPT), open field test (OFT), tail suspension test (TST), and forced swim test (FST) to evaluate the antidepressant effects. The abundance of Desulfovibrio in mouse intestines was quantified using quantitative polymerase chain reaction (q-PCR). Targeted metabolomic analysis of short-chain fatty acids (SCFAs) in mice was performed using GC-MS. Targeted metabolomic analysis of arachidonic acid (AA) in mice was conducted using LC-MS. Additionally, histopathological changes in mouse colon tissue were observed via HE staining. RESULTS: Q-PCR analysis revealed a significant increase in the abundance of Desulfovibrio in the intestinal tract of mice in the model group, indicating successful colonization of Desulfovibrio in these animals. Behavioral results indicated that intervention with Desulfovibrio significantly induced behavioral phenotypes of anhedonia, reduced spontaneous activity, and behavioral despair in mice, demonstrating its direct role in promoting depression-like phenotypes. Histological findings revealed disordered colonic gland structures, epithelial damage, and increased inflammatory cell infiltration in the model group, suggesting impaired intestinal barrier function. Metabolomic analysis showed that Desulfovibrio intervention reshaped the serum short-chain fatty acid profile, with butyrate decreased and propionate increased. Concurrently, arachidonic acid metabolism shifted toward a pro-inflammatory state, evidenced by elevated levels of pro-inflammatory mediators such as Prostaglandin E2 (PGE2) and Leukotriene B4 (LTB4), while the anti-inflammatory substance Docosahexaenoic Acid (DHA) was reduced. CONCLUSION: Desulfovibrio trigger depression-like behaviors in mice by disrupting the colonic barrier structure, perturbing the short-chain fatty acid metabolic profile, and activating the pro-inflammatory arachidonic acid metabolic pathway. To further explore the relationship between gut microbiota and the onset of depression, depression model animals were used, revealing that Desulfovibrio may serve as a potential intervention target for depression.
-
The brain-adipocyte-gut network: Linking obesity and depression subtypes.
Major depressive disorder (MDD) and obesity are dominant and inter-related health burdens. Obesity is a risk factor for MDD, and there is evidence MDD increases risk of obesity. However, description of a bidirectional relationship between obesity and MDD is misleading, as closer examination reveals distinct unidirectional relationships in MDD subtypes. MDD is frequently associated with weight loss, although obesity promotes MDD. In contrast, MDD with atypical features (MDD-AF) is characterised by subsequent weight gain and obesity. The bases of these distinct associations remain to be detailed, with conflicting findings clouding interpretation. These associations can be viewed within a systems biology framework-the psycho-immune neuroendocrine (PINE) network shared between MDD and metabolic disorders. Shared PINE subsystem perturbations may underlie increased MDD in overweight and obese people (obesity-associated depression), while obesity in MDD-AF (depression-associated obesity) involves more complex interactions between behavioural and biomolecular changes. In the former, the chronic PINE dysfunction triggering MDD is augmented by obesity-dependent dysregulation in shared networks, including inflammatory, leptin-ghrelin, neuroendocrine, and gut microbiome systems, influenced by chronic image-associated psychological stress (particularly in younger or female patients). In MDD-AF, behavioural dysregulation, including hypersensitivity to interpersonal rejection, fundamentally underpins energy imbalance (involving hyperphagia, lethargy, hypersomnia), with evolving obesity exaggerating these drivers via positive feedback (and potentially augmenting PINE disruption). In both settings, sex and age are important determinants of outcome, associated with differences in emotional versus cognitive dysregulation. A systems biology approach is recommended for further research into the pathophysiological networks underlying MDD and linking depression and obesity.
-
Compound Chaijin Jieyu Fang alleviates insomnia complicated with depression by reshaping actinobacteria to inhibit neuronal apoptosis.
OBJECTIVE: This study aimed to investigate the intervention effect of Compound Chaijin Jieyu Fang (CCJF) on insomnia complicated with depression, focusing on restoring gut microbiota balance, particularly the Actinobacteria, which is implicated in the dysregulation of the tryptophan metabolic pathway. This imbalance contributes to neuronal apoptosis, exacerbating the symptoms of insomnia complicated with depression. METHODS: A Mendelian randomization analysis was conducted to explore the causal relationships between insomnia and depression, as well as the mediating role of gut microbiota. The chemical constituents of CCJF were identified using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). A Sleep Deprivation and Chronic Unpredictable Mild Stress (SD + CUMS) rat model was established, and a comprehensive array of methodologies-including behavioral assessments, 16S rRNA sequencing, immunohistochemistry, HE staining, Western blot, ELISA, high-performance liquid chromatography, TUNEL staining, and transmission electron microscopy-was employed to systematically evaluate the effects of CCJF on gut microbiota, tryptophan metabolism, and neurological function. RESULTS: In behavioral experiments, the administration of CCJF notably enhanced sleep quality, cognitive function, and mood state in rats. The CCJF intervention effectively regulated the actinobacteria imbalances, facilitated the production of indole derivatives such as indole-3-acetic acid (IAA) and indole-3-lactic acid (ILA), and activated the aryl hydrocarbon receptor (AhR) pathway. Furthermore, the inhibition of the kynurenine pathway resulted in decreased production of kynurenine 3-monooxygenase (KMO), 3-hydroxykynurenine (3-HK), quinolinic acid (QA), and the NR2B subunit of the N-methyl-d-aspartate (NMDA) receptor. This inhibition contributed to the amelioration of damage to the intestinal barrier and the blood-brain barrier under stress, while also reducing neurotoxicity. Additionally, the intervention promoted the conversion of tryptophan to 5-hydroxytryptamine (5-HT) and melatonin synthesis, and modulated key apoptotic and neurotrophic pathways. These effects collectively reduced neuronal apoptosis, restored synaptic function, and enhanced neuroplasticity. CONCLUSION: CCJF effectively alleviated insomnia complicated with depression by reshaping the actinobacteria, rectifying the shift in the tryptophan metabolic pathway, and attenuating hippocampal neuronal apoptosis. This study provides a new theoretical basis for the study of the mechanism of insomnia complicated with depression and the intervention of traditional Chinese medicine, as well as a potential therapeutic target.
-
The Interplay Between Depression, Probiotics, Diet, Immunometabolic Health, the Gut, and the Liver-A Secondary Analysis of the Pro-Demet Randomized Clinical Trial.
(1) Background: Depression, metabolic alternations, and liver diseases are highly comorbid. Studies have shown that probiotics might be helpful in the treatment of the above-mentioned states. The aim of this secondary analysis was to search for possible predictors of probiotics' efficacy on liver-related outcome measures. (2) Methods: Data from 92 subjects from a randomized clinical trial on the effect of probiotics on depression were analyzed. The shift in liver steatosis and fibrosis indices was assessed in the context of baseline immunometabolic, psychometric, dietary, and intestinal permeability factors. Correlation analysis and linear regression models were used. (3) Results: A total of 30% of the variance of the improvement in the score of the aspartate transferase to platelet ratio index was explained by probiotic use, higher pre-intervention triglycerides, cholesterol, C-reactive protein levels, increased cereal intake, and a lower consumption of sweets. Then, the model of the change in alanine transferase indicated that probiotics were efficient when used by subjects with higher basal levels of intestinal permeability markers. (4) Conclusions: Probiotics being used along with a healthy diet may provide additional benefits, such as decreased cardiovascular risk, for patients with measures consistent with the immunometabolic form of depression. Probiotic augmentation may be useful for liver protection among subjects with a suspected "leaky gut" syndrome. ClinicalTrials.gov: NCT04756544.