Heliyon
·
2023
·
IF 4
Chuan Jiang,Chaonan Wang,Weizhong Qu,Yuanyuan Wang,Hua Wang,Xin Wei,Mingyan Wang,Qianqian He,Yihan Wang,Lirong Yuan,Yonggang Gao
Depression is a complex and prevalent mental illness. Cherry leaf is a traditional Chinese herbal medicine, which has confirmed to exert a certain antidepressant effect, but its potential neural regulation mechanism is not clear. This paper aims to investigate the improved action of cherry leaf decoction (CLD) on chronic unpredictable mild stress (CUMS) rats and its potential neural regulation mechanism by verifying the role and function of NMDAR regulatory target α2δ-1 in depression due to CUMS. Male SD rats were subjected to random stressors persisting for 5 weeks to establish the CUMS depression rat model. CLD could effectively alleviate depression-like behaviors of CUMS rats in behavioral tests including sucrose preference test, forced swimming test, tail suspension test and open field test. After the administration of the CLD, the expression of corticotropic-releasing hormone (CRH) in the hypothalamus was inhibited. Moreover, the levels of CRH, adrenal cortical hormone (ACTH) and corticosterone (CORT) in serum also decreased significantly. CUMS upregulated the expressions of α2δ-1, N-methyl- d -aspartate receptor 1 (NR1), NR2A and NR2B, and enhanced the binding ability to of α2δ-1 and NR1, which were reversed by CLD. The results demonstrated that CLD could ameliorate depression-like behaviors due to CUMS, which was related to the fact that CLD down-regulated α2δ-1 level and interfered with α2δ-1 binding to NR1, thereby reducing NMDAR expression and ultimately inhibiting HPA axis activity.
研究领域:
神经科学
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中药学
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精神医学
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DOI
高影响因子
MOLECULAR NUTRITION & FOOD RESEARCH
·
2021
·Vol. 65
·期 16
·2100146
·
IF 5.82
Yanqiu Chen,Mei Wan,Yi Zhong,Tingfang Gao,Yuehan Zhang,Fen Yan,Da Huang,Yuanzi Wu,Zuquan Weng
Scope Depression is the leading cause of disability around the world; however, most antidepressants have drug tolerance and serious side effects. In this study, it is explored whether partially hydrolyzed guar gum (PHGG) is a safe food that exhibits protection in a mouse model of depression. Methods and Results PHGG is orally administered to mice with depression induced by chronic unpredictable mild stress (CUMS) in two animal experiments (prevention trial and intervention trial) to characterize the potentially protective effect of PHGG. The results in the prevention trial show that PHGG significantly inhibits the loss of body weight, and prevents CUMS-induced depressive-like behavior in mice. The beneficial effects may be associated with PHGG modulating the gut microbiota structure and then increasing the levels of short-chain fatty acids in mice feces and the levels of 5-hydroxytryptamine and dopamine in serum, striatum, and hippocampus. Besides, PHGG in the intervention trial is less effective than that in the prevention trial, but it may have a synergistic effect on improving depression with fluoxetine. Conclusions This study suggests that moderate daily intake of PHGG can contribute to relieving depressive-like behavior.
研究领域:
营养学
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神经科学
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微生物学
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产品关联
DOI
PubMed
高影响因子
BRAIN RESEARCH
·
2024
·
IF 2.7
Xinliu Wang,Xin Zhang,Wei Xie,Yuanyuan Wang,Shuxian Zang,Ziyun Ban,Depei Li,Yugai Jia,Yonggang Gao
Depression is a common mental illness, which is highly related to intestinal motor dysfunction and causes a global burden of disease. Lindera aggregata (LA), a traditional medicinal herb, has been used to treat gastrointestinal disorders; however, the effect of LA on depression remains unclear. Here, we assessed the impact of LA on chronic unpredictable mild stress (CUMS)-induced depression in mice and explored the related mechanisms. The results showed that LA ameliorated depressive behaviors in mice exposed to CUMS, as evidenced by improved performance in the sucrose preference test, force swimming test, and open field test, as well as increased serum levels of adrenocorticotropic hormone and 5-hydroxytryptamine. In addition, LA increased the serum levels of D-xylose and ghrelin, indicating that LA can promote gastrointestinal motility. Additional studies revealed that LA relieved CUMS-induced hippocampal tissue damage, as shown by hematoxylin and eosin and Nissl staining. LA increased the expression levels of brain-derived neurotrophic factor (BDNF) and promoted the activation of tropomyosin receptor kinase B (TrkB) and cAMP response element-binding (CREB) in the hippocampus of CUMS-exposed mice or in corticosterone-injured HT22 cells. In conclusion, LA can improve CUMS-induced depressive behavior in mice, potentially through hippocampal neuroprotection mediated by the BDNF/TrkB/CREB signaling pathway, which also contributes to improved intestinal function.
研究领域:
药理学
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神经科学
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精神病学
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胃肠病学
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产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2024
·
IF 4.2
Fengjiao Liu,Yaxin Jia,Liwei Zhao,Li-na Xiao,Xizhen Cheng,Yingying Xiao,Ying Zhang,Yuling Zhang,Huimin Yu,Qiao-en Deng,Yuanyuan Zhang,Yimeng Feng,junfang Wang,Yonggang Gao,Xuan Zhang,Yunyun Geng
Major depressive disorder (MDD) is a prevalent psychiatric disorder associated with brain inflammation and neuronal damage. Derived from the Aesculus chinensis Bunge fruit, escin has shown anti-inflammatory and neuroprotective effects. However, its potential as a treatment for MDD is unclear. This study investigates the antidepressant properties of escin using in vivo experimentation. The chronic unpredictable mild stress (CUMS) model was used to analyze the potential antidepressant effects and underlying mechanisms of escin. Wistar rats were exposed to CUMS for 35 consecutive days to induce MDD. The rats were then given either escin (1, 3, and 10 mg/kg) or fluoxetine (2 mg/kg) on a daily basis. Notably, escin significantly alleviated the depressive behaviors induced by CUMS, as evaluated through a series of behavioral assessments. Moreover, escin administration reduced TNF-α, IL-1β, and IL-6 levels in the hippocampus. It also decreased serum adrenal cortical hormone (ACTH) and corticosterone (CORT) levels while increasing 5-HT and Brain-derived neurotrophic factor (BDNF) levels in the CUMS rats, as measured by the enzyme-linked immunosorbent assay (ELISA). Pathological changes in the hippocampal regions were identified through Nissl staining, and Western blotting was used to quantify the protein levels of BDNF, TrkB, CREB, TLR4, MyD88, and NF-κB. Escin mitigated neuronal injury, elevated TrkB, BDNF, and CREB, and reduced TLR4, MyD88, and NF-κB protein levels in CUMS rats. The data from this study suggest that escin holds the potential for alleviating depression-like symptoms induced by CUMS. This effect may be mediated through the modulation of two signaling pathways, BDNF/TrkB/CREB and TLR4/MyD88/NF-κB.
研究领域:
药理学
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神经科学
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精神病学
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免疫学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2023
·
IF 5.4
Jiaqi Xie,Yihong Li,Yulu Liang,Hongqian Kui,Can Wang,Jianmei Huang
Ethnopharmacological relevance Platycladi Semen was recorded in Shen Nong's Herbal Classic and was considered a herbal medicine with low toxicity after long-term medication. Multiple traditional Chinese medicine prescriptions containing Platycladi Semen have been used to treat insomnia. Modern clinical practitioners commonly use Platycladi Semen to treat anxiety disorders, but there are few studies on its composition and anxiolytic mechanisms. Aim of the study To describe the main components of Platycladi Semen and investigate its anxiolytic effects and mechanisms. Materials and methods The main components of Platycladi Semen were characterized by liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS). The anxiolytic effects of oral Platycladi Semen were evaluated in chronic unpredictable mild stress (CUMS) induced mice. To explore the anxiolytic mechanisms of Platycladi Semen , serum non-targeted metabolomics combined with network pharmacology and molecular docking was performed. Results Fourteen compounds were identified in the 50% methanol extract and 11 fatty acid derivatives were identified in the methyl-esterified fatty oil of Platycladi Semen . In CUMS mice, both the aqueous extract and fatty oil of Platycladi Semen had anxiolytic effects, which were shown by the increase in the time and frequency of mice entering the open arm in the elevated plus maze (EPM) experiment. Through serum non-targeted metabolomics, 34 differential metabolites were identified, and lipid metabolic pathways such as sphingolipid metabolism, steroidogenesis, alpha-linoleic acid, and linoleic acid metabolism were enriched. Through network pharmacology, 109 targets of the main components in Platycladi Semen were identified, and the ‘neuroactive ligand-receptor interaction’ and ‘lipid metabolism’ were enriched. The molecular docking results showed that the main components in Platycladi Semen could bind to the key targets such as peroxisome proliferator-activated receptor delta (PPARD), peroxisome proliferator-activated receptor alpha (PPARA), fatty acid binding protein 5 (FABP5), fatty acid binding protein 3 (FABP3), peroxisome proliferator-activated receptor gamma (PPARG), arachidonate 5-lipoxygenase (ALOX5) and fatty acid amide hydrolase (FAAH). Conclusion This study indicated that Platycladi Semen has anxiolytic effects, and the anxiolytic mechanisms may be the regulation of lipid metabolism and the neuroactive ligand-receptor interaction.
研究领域:
药理学
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代谢组学
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中药学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
PSYCHONEUROENDOCRINOLOGY
·
2025
·
IF 3.6
Zhaoke Ling,Qingqing Kong,Zhiqiang He,Xin Hao,Ruiyao Liu,Jie Liu,Yushi Wang,Jiao Liu,Wenlong Du,Yi Liu
The pathogenesis of depression is associated with synaptic impairment and dysfunction in autophagy processes. Mendelian randomization (MR) analysis revealed that six GWAS IDs revealed a significant association between Beclin-1 levels and depression risk. Besides, all SNPs had a positive effect on depression risk. Analyzing neurons from depressed individuals using single-cell RNA sequencing (scRNA-seq) uncovered decreased expression of AKT, mTOR, and genes linked to synaptic plasticity. The activation of the PI3K/AKT/mTOR signaling has been demonstrated to control autophagy and have a protective effect on the nervous system. Hydrogen sulfide (H 2 S) is an endogenous gasotransmitter that can potentially treat various neurological disorders by improving neuronal synaptic plasticity. However, whether H 2 S regulates autophagy through PI3K/AKT/mTOR signaling, improves neuronal synaptic plasticity damage, and plays an antidepressant role is unclear. Our current research revealed that the reduction in the expression of p-PI3K, p-AKT, and p-mTOR proteins increase in neuronal autophagy activity and decline synaptic plasticity in mice with depression induced by chronic unpredictable mild stress (CUMS). Treatment with the exogenous hydrogen sulfide donor NaHS for one day and continuous treatment for one week improved the depression-like behaviors in the mice. Compared with those after one day of NaHS treatment, the above protein expression levels were restored and maintained, and the antidepressant effect was more significant after one week of continuous treatment with NaHS. Moreover, the PI3K inhibitor LY294002 was used to demonstrate that NaHS suppresses autophagy through activating the PI3K/AKT/mTOR signaling and ameliorates synaptic plasticity impairments. This study provides novel insights into the antidepressant mechanisms of H 2 S, highlighting its antidepressant therapeutic potential.
研究领域:
神经科学
·
分子生物学
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药理学
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DOI
PubMed
高影响因子
Food Science & Nutrition
·
2026
·Vol. 14
·期 6
·e71912
·
IF 5
Yanni Wang,Zhaorong Yue,Manjie Xu,Wenjun Xu,Weizhong Zhang,Xiaolong Li,Qinghong Liu,Kailong Guan,Zewen Zhang,Yang Li,Xin Wang,Hongyu Li
Chinese Kushui Rose ( Rosa sertata × Rose rugosa ) is widely recognized for its medicinal and edible properties, and Chinese Kushui Rose Essential Oil (KREO) has attracted growing attention due to its potential anxiolytic and sedative-hypnotic effects. This study aims to systematically evaluate the preventive effects of KREO against depression-like behaviors and explore its underlying mechanisms. We identified 57 volatile compounds from KREO using gas chromatography–mass spectrometry (GC–MS), with the major constituents being citronellol, geraniol, and citronellyl acetate. In mice with chronic unpredictable mild stress (CUMS)-induced depression, administration of KREO facilitated body weight recovery, alleviated depressive-like behaviors, and improved voluntary locomotor activity and exploratory behavior. Mechanistic investigations revealed that KREO increased hippocampal levels of serotonin (5-HT) and brain-derived neurotrophic factor (BDNF), reduced serum corticosterone (Cort) concentrations, and upregulated the expression of tyrosine receptor kinase B (TrkB) as well as the phosphorylation of extracellular signal-regulated kinase 1/2 (p-ERK1/2) in the hippocampus. Thus, KREO prevents depression-like behavior by enhancing monoaminergic neurotransmission and attenuating hypothalamic–pituitary–adrenal (HPA) axis hyperactivity, with these effects associated with activation of the BDNF signaling pathway. These findings support the potential of KREO as a therapeutic intervention for depression and as a functional dietary ingredient.
✓ 已验证
DOI
PubMed
高影响因子
EXPERIMENTAL GERONTOLOGY
·
2024
·
IF 3.3
Baoying Wang,Lei Tian,Mengdi Wu,Duo Zhang,Xiangli Yan,Ming Bai,Yucheng Li,Pan Su,Erping Xu
The NLRP3 inflammasome is critically involved in the development of depression. The E3 ubiquitin ligase TRIM31 negatively regulates this process by promoting the degradation of NLRP3 through the ubiquitin-proteasome pathway. Modified Danzhi Xiaoyaosan (MDZXYS) has shown good therapeutic effect in both preclinical and clinical depression treatments, yet the underlying mechanisms of its antidepressant effects are not fully understood. In the present study, we aimed to explore the antidepressant mechanisms of MDZXYS, focusing on NLRP3 activation and ubiquitin-mediated degradation. We employed rats with depression induced by chronic unpredictable mild stress (CUMS) and conducted various behavioral tests, including the sucrose preference, forced swimming, and open field tests. Neuronal damage in CUMS-treated rats was assessed using Nissl staining. We measured proinflammatory cytokine levels using ELISA kits and analyzed NLRP3/TRIM31 protein expression via Western blotting and immunofluorescence staining. Our results disclosed that MDZXYS reversed CUMS-induced depression-like behaviors in rats, reduced proinflammatory cytokine levels (IL-1β), and ameliorated neuronal damage in the prefrontal cortex. Additionally, CUMS activated the NLRP3 inflammasome in the prefrontal cortex and upregulated the protein expression of TRIM31. After MDZXYS administration, the expression of NLRP3 inflammasome-associated proteins was reduced, while the expression level of TRIM31 was further increased. Through co-localized immunofluorescence staining, we observed a significant elevation in the co-localization expression of NLRP3 and TRIM31 in the prefrontal cortex of the MDZXYS group. These findings suggest that inhibiting NLRP3 inflammasome-mediated neuroinflammation by modulating the TRIM31signaling pathway may underlie the antidepressant effects of MDZXYS, and further support targeting NLRP3 as a novel approach for the prevention and treatment of depression.
研究领域:
神经科学
·
药理学
·
精神病学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
npj Science of Food
·
2025
·
IF 7.8
Peng Ying,Yu Tianxing,Qin Chunyin,Li Feilong,Xu Zhuoqi,Fang Qi,Cheng Anqi,Zhai Xiaoting,Fu Xiaoping,Li Daxiang,Hu Shanshan
Depression has emerged as a major global public health issue. l -theanine exerts notable anxiolytic and antidepressant effects mediated by its blood-brain barrier permeability as well as its anti-inflammatory and antioxidant properties. Nevertheless, the underlying mechanism of its key role remains elusive. In this study, chronic unpredictable mild stress (CUMS) reduced serum neurotransmitter levels in mice, impaired prefrontal cortex (PFC) and colonic barrier function, which induced depressive-like behaviors. l- theanine, especially at a dose of 800 mg/kg, down-regulated gut-brain inflammatory pathways (TLR9/NLRP3/Caspase-1) and restored barrier integrity (ZO-1 and Occludin), reversing CUMS-induced depressive-like behavior. This therapeutic effect was primarily attributed to l- theanine-mediated reshaping of gut microbiota (increased of Lactobacillus and Roseburia ) and the restoration of short-chain fatty acids (SCFAs, especially acetic acid, butyric acid, and propionic acid) synthesis and their receptor functions. In summary, the Gut-SCFAs-Brain axis may serve as a potential pathway for l -theanine to improve depression.
研究领域:
神经科学
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精神病学
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肠-脑轴研究
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微生物组学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
·
2023
·
IF 5.3
Li Liu,Rong Zhang,Chang Chen,Changbo Xia,Guangda Yao,Xiaogang He,Baomei Xia
It has been reported that Banxia-houpo decoction (BXHPD) serves as the anti-depressant treatment for a mild and severe depressive disease with limited side effects. The present study was performed to evaluate the protective effect of BXHPD on chronic unpredicted mild stress (CUMS)-induced depression and explore its effect on TrkA/Akt-mediated microglia polarization. The CUMS procedure was carried out, and the mice were intragastrically treated with BXHPD once daily. The selective TrkA inhibitor GW441756 was applied to further investigate the role of TrkA in BXHPD-mediated microglia polarization. The behaviour test including open field test (OFT), sucrose preference test (SPT), novelty-suppressed feeding test (NSFT), tail suspension test (TST) and forced swim test (FST) was performed. The concentrations of pro-inflammatory cytokines IL-6, TNF-α, IL-1β, IL-12 and anti-inflammatory cytokines IL-4, IL-10 were determined using Enzyme-linked immunosorbent assay. The population of Iba1+ cells and the length of microglia processes were observed under the fluorescence microscope. The mRNA expressions of Arg1, Ym1 and Fizzl1 were measured by PCR. The protein expressions of TrkA, p-Tyr490-TrkA, p-Ser473-Akt, p-Ser473-Akt1, p-Ser474-Akt2, p-CREB and Jmjd3 were detected by western blot. Our results showed that BXHPD attenuated CUMS-induced depressive-like behaviour, promoted anti-inflammatory cytokines, inhibited pro-inflammatory cytokines, suppressed microglia activation, promoted M2 phenotype-specific indices and upregulated the expressions of TrkA, p-Tyr490-TrkA, p-Ser473-Akt, p-Ser473-Akt1, p-Ser474-Akt2, p-CREB and Jmjd3. The above beneficial effect of BXHPD can be blocked by TrkA inhibitor GW441756. This work demonstrated that BXHPD exerted an anti-depressant effect by promoting M2 phenotype microglia polarization via TrkA/Akt pathway.
研究领域:
药理学
·
神经科学
·
精神病学
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2026
·
IF 5.6
Hanchun Yan,Wei Wang,Xinhua Song,Yaqi Wang,Zhaowen Nie,Honghan Zhang,Hao Duan,Ningyuan Li,Yuqi Feng,Yuhui Zhang,Chao Wang,Zhongchun Liu
Background The underlying mechanisms of major depressive disorder (MDD) remain unclear; however, increasing evidence has linked MDD to blood–brain barrier (BBB) dysfunction. This study aimed to determine whether BBB impairment represents an early pathological change during chronic stress and whether preservation of BBB integrity is associated with attenuation of neuroinflammatory and behavioral abnormalities. Methods We employed a time-course (1, 2, and 4 weeks) chronic unpredictable mild stress (CUMS) model in C57BL/6 J mice. Depressive-like behaviors (SPT, FST, TST, OFT), BBB permeability (Evans blue), tight junction (TJ) protein expression (qPCR, Western Blot), ultrastructure (TEM, IF), peripheral and central inflammatory responses (ELISA, qPCR, IF), and transcytosis-related changes (Western Blot, TEM) were systematically assessed at each time point. In separate intervention experiments, the PDGFRβ inhibitor Imatinib (50 mg/kg/d) or an MMP-9 inhibitor (20 mg/kg/d) was administered throughout the 4-week CUMS procedure. Results Depressive-like behaviors became robustly established by week 4. In contrast, BBB disruption occurred earlier: molecular changes (e.g., Claudin-5 protein loss) were significant at week 1, followed by functional permeability, TJ structural disruption, increased endothelial vesicle density, and inflammatory alterations at week 2. This pathology worsened by week 4. The 4-week Imatinib co-treatment attenuated the development of depressive-like behaviors, alleviated BBB disruption, and reduced neuroinflammatory abnormalities. At the molecular level, CUMS induced a time-dependent upregulation of MMP-9. Imatinib treatment attenuated activation of the PDGFRβ/MMP-9 pathway, whereas MMP-9 inhibition preserved BBB integrity and attenuated central inflammatory abnormalities despite persistently elevated peripheral cytokine levels. Conclusion BBB dysfunction is an early pathological event during chronic stress and is associated with both tight junction disruption and transcytosis-related alterations. Pharmacological preservation of BBB integrity was accompanied by reduced neuroinflammation, consistent with BBB integrity being an important modulator of chronic stress-associated central inflammatory abnormalities. The PDGFRβ/MMP-9 pathway may represent a promising mechanism associated with stress-related BBB injury and a potential therapeutic target.
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF AFFECTIVE DISORDERS
·
2025
·
IF 4.9
Huiying Xie,Yan Xue,Rui Deng,Liuxiang Chen,Yiyi Wang,Jia Xu,Hao Liu,Xingxing Li,Wei Cui,Jun-Fang Zhang
Background Stress is a significant trigger of depression, and miR-124 has been implicated in stress-induced depression, while the underlying molecular mechanisms remain unclear. Methods We established mouse depression models using chronic restraint stress (CRS) and chronic unpredictable mild stress (CUMS), and the HT-22 cell models with corticosterone (CORT) and glutamate (Glu). Depression-like behaviors were assessed using the forced swimming test, tail suspension test, and sucrose preference test. Adeno-associated viruses were employed to manipulate miR-124 and ubiquitin-specific protease 14 (USP14) expression. mRNA levels of miR-124 , Usp14 , and Rest were measured by qRT-PCR, the interaction between miR-124 and Usp14 mRNA was assessed by luciferase reporter assays, protein expression and interaction of USP14 and repressor element 1 silencing transcription factor (REST) were detected by western blotting, ubiquitination assay and co-immunoprecipitation. Immunofluorescence visualized altered REST expression in hippocampal neurons. Results CRS and CUMS robustly increased miR-124 levels in the hippocampus, while decreasing the USP14 and REST expression. Similar expression changes were seen in CORT- and Glu-treated HT-22 cells. Mice with miR-124 overexpression but not inhibition in the hippocampus exhibited notable depression-like behavior. Mechanistically, miR-124 directly targeted USP14, reduced USP14 binding to REST, thereby increasing REST ubiquitination and degradation. Inhibition of miR-124 produced antidepressant-like effects and restored the expression and interaction of USP14 and REST in the CRS and CUMS mice. Furthermore, overexpression of USP14 alleviated depression-like behaviors and low REST levels. Conclusion Hippocampal miR-124 mediates depression-like behavior under chronic stress via regulating the USP14/REST signaling pathway, highlighting its potential as a therapeutic target.
研究领域:
神经生物学
·
分子精神病学
·
信号转导
·
表观遗传学
·
应激生理学
·
神经药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）