ACS Omega
·
2025
·
IF 4.3
Yusen Xu,Xuemei Han,Ying Zhu,Bin Deng,Linjie Li,Yujing Du,Yanjie Qin,Yongning Lv,Xuejia Zhai
Traditional Chinese medicine Chaihu Shugan San (CSGS) is a classic Chinese herb prescription for improving depression, but its specific molecular mechanism has not been fully clarified. This study integrates network pharmacology and experimental validation to investigate CSGS’s antidepressant effects, focusing on its impact on GC metabolism and related pathways. In this research, the antidepressant mechanism of CSGS in relation to the depression model induced by chronic unpredictable mild stress will be discussed. High-performance liquid tandem mass spectrometry was applied for the verification of the grown metabolites’ economic vitality in rat plasma and the prefrontal cortex. The revelation of behavioral test results showed that the administration of CSGS improved depression symptoms significantly at the end of the administration period, which was 8 weeks. Network pharmacology was used to assist in verifying and improving the mechanism by which the active ingredients of CSGS affect the glucocorticoid metabolic pathway to exert antidepressant effects. CSGS significantly improved glucocorticoid (GC) metabolism by reducing corticosterone (CORT) levels and increasing dehydrocorticosterone (11-DHCORT) and the 11-DHCORT/CORT ratio in plasma and PFC. It regulated GC metabolism in the liver and PFC by downregulating GC synthase (11β-HSD1) and upregulating GC metabolic enzymes (11β-HSD2). Additionally, CSGS restored GC signaling by upregulating GR and HSP-90α, downregulating FKBP51 and HSP-70, and alleviating inflammation by inhibiting NF-κB P65 and HAT expression. These effects, particularly in the liver and PFC, were stronger than those with fluoxetine. Network pharmacology revealed that CSGS targets multiple pathways including PI3K-Akt, FoxO, HIF-1, and mTOR. These results indicate that CSGS can improve the depressive state of rats by regulating glucocorticoid metabolism and other related pathways as well as downstream signaling proteins.
研究领域:
中药学
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神经生物学
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药理学
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DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2022
·
IF 5.195
Xiaohui Jin,Leilei Zhu,Shuaifei Lu,Caiyin Li,Ming Bai,Erping Xu,Jiduo Shen,Yucheng Li
Mitochondrial dysfunction has been reported to be involved in the pathogenesis of depression, and mitophagy is a key pathway for mitochondrial quality control. This study aimed to investigate the effect of baicalin on mitophagy in the hippocampus of mice exposed to chronic unpredictable mild stress (CUMS) and explore its potential mechanism. After exposure to CUMS for 6 weeks, mice were given baicalin (20 mg/kg) or fluoxetine (20 mg/kg) by oral gavage for 4 weeks, and HT22 cells were injured by corticosterone (CORT) in vitro. Depression-like behaviors were assessed by sucrose preference test and tail suspension test . The mitochondrial structure was observed by transmission electron microscopy . Detection of mitophagy and mitophagy-related protein by mitophagy kit and Western blot . The results showed that baicalin improved depressive-like behaviors in CUMS mice, and ameliorated mitochondrial structural impairment in the hippocampus neuron. Baicalin significantly down-regulated light chain 3(LC3)II/I, protein sequestosome 1 (P62), and translocase of the outer membrane 20 (TOM20), and up-regulated Nip-like protein (NIX), Adenylate activated protein kinase (AMPK), and Peroxisome proliferator-activated receptor-gamma coactivator (PGC)-1α. Furthermore, molecular docking showed that baicalin interacts with AMPK through hydrogen bonding. Baicalin increased NIX and AMPK, and improved mitophagy level and mitochondrial function in HT22 cells. Treatment with Phorbol 12-Myristate 13-acetate demonstrated that up-regulation of NIX ameliorated CORT-induced mitochondrial dysfunction in HT22 cells. In conclusion, the present study suggested that the antidepressant effect of baicalin may be related to the enhancement of NIX-mediated mitophagy through activating the AMPK/PGC-1α pathway by directly binding to AMPK.
研究领域:
神经科学
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药理学
·
分子生物学
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DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2019
·
IF 3.414
Bojun Chen,Jijun Li,Yuhuan Xie,Xi Ming,Gang Li,Jinjin Wang,Meng Li,Xiaohong Li,Lei Xiong
Ethnopharmacological relevance Cang-ai volatile oil (CAVO) is a traditional Chinese medicine (TCM) inhalational preparation for the treatment of some depressive and emotive disorders. Aim of the study This research aimed to evaluate the efficiency and possible mechanism of intranasal CAVO administration on depression in chronic unpredictable mild stress (CUMS)-induced rats compared to lavender volatile oil (LVO) treatment after CUMS exposure and bilateral olfactory bulb impairment (OBI) in rats. Materials and methods Forty depressive-like model rats induced by CUMS were evaluated by the forced swim test (FST), open field test (OFT), and sucrose preference test (SPT). The model rats were divided into five groups: CUMS (n = 8), CAVOh + CUMS (n = 8), CAVOl + CUMS (n = 8), LVO + CUMS (n = 8), and OBI + CAVO + CUMS (n = 8). The CUMS-induced rats were treated for a period of 4 weeks. The other healthy rats were regarded as the control (CTR, n = 8) subjects. The levels of serotonin (5-HT) and dopamine (DA) and their respective metabolites homovanillic acid (HVA) and 5-hydroxyindol acetic acid (5-HIAA) were measured in brain tissue homogenates of CUMS-induced rats using enzyme-linked immunosorbent assay (ELISA). Results CAVO ameliorated depressive-like behaviors (p < 0.05 ). The levels of DA in the CUMS group were lower than those in the CTR and CAVOh groups (** p < 0.01 and * p < 0.05 ). The levels of HVA were lower in the CUMS group than in the CTR, LVO, OBI + CAVOh and CAVOh groups (** p < 0.01 and * p < 0.05 ) and lower in the OBI + CAVOh group than in the CAVOh group (** p < 0.01 ). The levels of 5-HT in the CUMS group were lower than those in the CTR and CAVOh groups (** p < 0.01 ). The levels of 5-HIAA were lower in the CUMS and OBI + CAVOh groups than in the CTR, LVO and CAVOh groups (** p < 0.01 ). Conclusions CAVO can improve depressive-like behaviors concomitant with the regulation of DA and 5-HT metabolism in the brains of CUMS-induced rats.
研究领域:
药理学
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神经科学
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中医
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DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2026
·
IF 5.7
Xinliu Wang,Shuxian Zang,Ziyun Ban,Yuxuan Zhang,Lingchen Hou,Xin Zhang,Yuanyuan Wang,Depei Li,Feiyu An,Yuqi Liu,Yugai Jia,Yonggang Gao
Depression is a common mental and mood disorder. Norisoboldine (NIB) has been shown to provide neuroprotective benefits. However, its potential antidepressant effects and underlying mechanisms remain to be elucidated. Our findings indicated that NIB ameliorates depressive behaviors and mitigates hippocampal neuronal damage induced by chronic unpredictable mild stress (CUMS). Numerous studies have corroborated the neuroprotective effects of gastrointestinal hormones such as ghrelin and its endogenous receptor, the growth hormone secretagogue receptor type 1a (GHSR-1a). Notably, NIB demonstrated minimal impact on the expression levels of ghrelin and GHSR-1a. We furtherly investigated whether NIB could directly activate GHSR-1a in vitro . Treatment with NIB increased cell viability and inhibited CORT-induced apoptosis in HT-22 cells in a dose-dependent manner. The use of a GHSR-1a antagonist and GHSR-1a knockdown weakened the inhibitory effect of NIB on cell apoptosis. NIB attenuated endoplasmic reticulum (ER) stress via GHSR-1a in HT-22 cells, thereby protecting against cell apoptosis and loss. Molecular docking results showed an interaction between NIB and GHSR-1a, and CESTA results showed that NIB increased the thermal stability of GHSR-1a. In conclusion, NIB can reduce ER stress-induced injury to hippocampal neurons through GHSR-1a and improve depressive behavior in mice induced by CUMS. Download: Download high-res image (317KB) Download: Download full-size image
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PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2026
·
IF 6.7
Zhang Xin,Wang Zhitong,Wu Sifan,Hao Jingyu,Jia Xiuzhen,Zhao Zifu,Duan Sufang,Liu Zhigang,Liu Xuebo,Lu Yanhui,Yuan Tian
Mulberry,
a traditional medicinal and edible plant rich in polysaccharides
and flavonoids, has potential in regulating emotional behaviors. This
study compared emulsified mulberry extract (EME) and aqueous mulberry
extract (AME) on anxiety- and depression-like behaviors in male C57BL/6J
mice exposed to chronic unpredictable mild stress (CUMS), and explored
the underlying mechanisms of EME. EME alleviated anxiety- and depression-like
behaviors more effectively than AME, with superior colloidal stability
and dispersion. Metabolomic profiling revealed higher relative abundances
of carbohydrates, eicosanoids, and flavonoids in EME. EME remodeled
the gut microbiota–short-chain fatty acid (SCFA) axis, enhanced
colonic barrier integrity, reduced serum lipopolysaccharide and proinflammatory
cytokines, decreased stress hormone levels, elevated 5-hydroxytryptamine,
and suppressed hippocampal glial activation while preserving neuronal
integrity. Correlation analyses linked gut microbiota, SCFAs, hypothalamic-pituitary-adrenal
axis activity, and behavioral phenotypes. These findings indicate
that emulsification enhances the bioactivity of whole-component mulberry
extracts, supporting their potential as natural food-based interventions
for emotional disorders.
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高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2024
·
IF 4.8
Chao Lu,Lingang Zhao,Liyuan Tian,Chenguang Lin,Lei Wu
Ethnopharmacological relevancy Chaihushugan san (CSS), a classic formula for soothing the liver and relieving depression, has been identified to produce rapid antidepressant-like effects in female mice. However, the gender predominance and underlying mechanisms of CSS's antidepressant remain unclear. Aim of the study In this study, we focused on unraveling the gender predominance of CSS in antidepressant and the specific neuronal mechanisms that mediate this predominance. Methods and materials Tail suspension test (TST), forced swimming test (FST) and sucrose preference test (SPT) were used to evaluate depressive phenotypes or antidepressant-like effects of CSS in female and male chronic unpredictable mild stress (CUMS) mice model. RNA-sequencing was used to screen specific target for CSS antidepressant gender dominance. RT-PCR and elisa were used to detect the expressions of specific molecule, hormones, and inflammatory factors in the hippocampus. hippocampal viral overactivation and pharmacological blockade were used to detect the correlation between CSS antidepressant gender dominance and related targets. Results In the present study, both female and male mice displayed depressive phenotypes including significant increasing immobility time in TST and reducing sucrose preference ratio in SPT after exposing CUMS for 3 weeks. However, acute administration of CSS (2, 4 g/kg) improved the depressive phenotypes only in female mice or not male mice at 2 h later. Moreover, the expressions of TC2N were increased only in female mice after exposing CUMS for 3 weeks, which were also reversed by CSS after a single administration 2 h later, but no alterations in male mice. The hippocampal expressions of estrogen receptor β (Erβ), pro-inflammatory factors (IL-1β and TNF-α) and anti-inflammatory factors (IL-10, TGF-β and IL-1Rα) were all abnormal in female CUMS mice model, which were all normalized by CSS. Furthermore, overactivation of hippocampal TC2N by AAV-TC2N +/+ blocked the antidepressant-like effects of CSS and the up-regulation of hippocampal Erβ in female mice. However, inhibition of Erβ blunted the antidepressant-like effects of CSS and CSS's suppression of pro-inflammatory factors (IL-1β and TNF-α), which had no any effect on hippocampal TC2N and anti-inflammatory factors (IL-10 and TGF-β). Conclusions The study revealed that CSS had antidepressant superiority in female mice depending on inhibiting hippocampal TC2N and then activating Erβ, further inhibiting the release of pro-inflammatory factors to produce antidepressant effects, which provided a basis for the guidance of CSS in clinical application, new ideas and targets for the development of drugs for depression with gender differences.
研究领域:
民族药理学
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神经科学
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药理学
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产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL PHARMACOLOGY
·
2025
·
IF 5.6
Tian-tian Wang,Meng-yuan Zhou,Xue-na Gong,Yan Huang,Fei-long Li,Sheng-long Gu,Man-yu Zhang,Ling-ling Li,Ze-shan Xu,Rong Li,Li Cai
Eupalinolide B (EB), a primary bioactive compound isolated from Eupatorium lindleyanum DC ., has exhibited various pharmacological properties, such as antitumor, anti-inflammatory, and notably, neuroprotective effects in neurodegenerative diseases. However, the in-depth studies on the antidepressant potential of EB and its underlying mechanisms are still lacking. Herein, we investigated the therapeutic effects of EB on corticosterone (CORT)-induced neurotoxicity in PC12 cells and its antidepressant-like effects in rats subjected to chronic unpredictable mild stress (CUMS). In particular, we focused on the molecular mechanisms related to modulating the GSK-3β/β-catenin pathway. Our findings revealed that EB promoted cell proliferation while decreasing apoptosis and oxidative stress in CORT-induced PC12 cells. In vivo, EB alleviated the depressive-like behaviors in CUMS rats, as assayed by the sucrose preference test, open field test, and forced swim test. Additionally, EB attenuated the hippocampal pathological damage and increased Ki67- and doublecortin-positive cell numbers in hippocampal dentate gyrus, thus restoring hippocampal neurogenesis in CUMS rats. The binding of EB to GSK-3β was confirmed using molecular docking and cellular thermal shift assays. Overexpression of GSK-3β diminished the therapeutic effects of EB on CORT-induced PC12 cells, further indicating that GSK-3β is the target of EB. Mechanistically, EB hindered GSK-3β activity and thus activated β-catenin signaling in both CORT-induced PC12 cells and CUMS rat hippocampus, as demonstrated by increased p-GSK-3β (Ser9), reduced p-β-catenin, and elevated β-catenin expression. Collectively, this study offers new insights into the antidepressant mechanisms of EB, highlighting its potential as a candidate for depression treatment.
研究领域:
神经科学
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药理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
BEHAVIOURAL BRAIN RESEARCH
·
2023
·
IF 2.7
Wenjie Chen,Yiping Chen,Muhammad Shahzad Aslam,Junliang Shen,Tao Tong,Simin Yan,Wenjing Cheng,Zichun Huang,Jiawei Li,Siyu Liu,Jianguo Li,Xianjun Meng
Background Depression is a severe emotional condition that significantly affects the quality of life. Acupuncture exerts preventive effects on depression in rats with post-chronic unpredictable mild stress (CUMS). Methods The study involved chronic unpredictable mild stress (CUMS) depression model mice to administer acupuncture as a preventative measure to investigate the mechanism of acupuncture's antidepressant and observe the effect of acupuncture on impact via the Lateral Habenula (LHb) and Gut-Liver-Brain Axis. The researcher investigated molecules correlating with a nitric oxide/cyclic guanosine monophosphate (NO/cGMP) pathway and assessed inflammation in the LHb and liver. In addition, 16 S rDNA bioinformatics study revealed the quantity and variety of gut microbiota. Rats were randomly divided into five groups: control (CON), CUMS, CUMS + acupuncture (AP), CUMS + fluoxetine (FX) and CUMS + N(G) -nitro -L- arginine methyl ester (LNAME) group. Except for the CON group, other rats were exposed to CUMS condition for 28 days. Simultaneously, manual acupuncture (at Fengfu and Shangxing acupoints, once every other day) and fluoxetine gavage (2.1 mg/kg, 0.21 mg/mL, daily) were conducted to the groups of AP and FX, respectively, after stressors. Rats in LNAME group were treated with LNAME normal saline (10 mg/kg, 1 mg/mL, i.p.) solution. Behavioural tests and biological detection methods were conducted sequentially to evaluate depressionlike phenotype in rats. Results The results showed CUMS induced depression-like behaviours, hyper-activation of NO/cGMP signaling pathway, inflammation in serum, LHb and liver, and dysbiosis of the gut microbiota. These changes could be prevented and ameliorated by acupuncture to varying extents. Conclusion Acupuncture prevented and attenuated depression-like phenotype induced by CUMS, possibly via regulating the NO/cGMP signaling pathway and thus improving inflammation in serum, LHb and liver, and gut microbiota dysbiosis. In addition, these can be evidence of the existence of the gut-liver-brain axis.
研究领域:
神经科学
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精神病学
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中医
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微生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2019
·
IF 2.983
Xue-Mei Han,Yan-Jie Qin,Ying Zhu,Xin-Lin Zhang,Nan-Xi Wang,Ying Rang,Xue-Jia Zhai,Yong-Ning Lu
Sensitive and comprehensive measurement of systemic metabolites of tryptophan, phenylalanine and glutamate metabolism in biological samples is effective for understanding the pathogenesis of depression and other neurological diseases. Therefore, this study developed an underivatized liquid chromatography tandem mass spectrometry (LC–MS/MS) method for simultaneous monitoring the 3 components of glutamate metabolism in rat hippocampus and 11 components of tryptophan and phenylalanine metabolism in rat hippocampus, plasma and urine, and applied it to investigate their changes in rats induced by chronic unpredictable mild stress (CUMS). The investigated analytes are as follows: tryptophan, serotonin, 5-hydroxyindoleacetic acid, kynurenine, kynurenic acid, xanthurenic acid, 3-hydroxyanthranilic acid, quinolinic acid, phenylalanine, tyrosine, tyramine, glutamate, glutamine and gamma-aminobutyric acid. The method was verified to be sensitive and effective with satisfactory linearity, accuracies in the range of 78.2%–120.4%, and precisions less than 17.8% for all identified analytes. A series of significant changes in CUMS-induced rats can be detected: tryptophan, serotonin and tyrosine levels decreased and quinolinic acid increased in both hippocampus and plasma. In addition, the kynurenine/tryptophan ratios increased in hippocampus and plasma, the kynurenic acid/quinolinic acid ratios of plasma and urine were significantly reduced. These findings demonstrated that the CUMS procedure could lead to the central and peripheral imbalances of tryptophan and phenylalanine metabolism. In conclusion, a LC–MS/MS method for simultaneous measurement of several neurotransmitters in rat hippocampus, plasma and urine was developed and successfully applied to investigation of the central and peripheral changes in CUMS-induced rats. The method would be expected to provide applicability to the study of the mechanisms of depression and other related diseases associated with these neurotransmitters.
研究领域:
神经科学
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分析化学
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药理学
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DOI
PubMed
高影响因子
BIOMEDICAL CHROMATOGRAPHY
·
2015
·Vol. 29
·期 11
·1737-1743
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IF 1.723
Xue-jia Zhai,Fen Chen,Chao-ran Zhu,Yong-ning Lu
Many amino acid neurotransmitters in urine are associated with chronic stress as well as major depressive disorders. To better understand depression, an analytical LC-MS/MS method for the simultaneous determination of 11 underivatized neurotransmitters (4-aminohippurate, 5-HIAA, glutamate, glutamine, hippurate, pimelate, proline, tryptophan, tyramine, tyrosine and valine) in a single analytical run was developed. The advantage of this method is the simple preparation in that there is no need to deconjugate the urine samples. The quantification range was 25–12,800 ng mL −1 with >85.8% recovery for all analytes. The nocturnal urine concentrations of the 11 neurotransmitters in chronic unpredictable mild stress (CUMS) model rats and control group ( n = 12) were analyzed. A series of significant changes in urinary excretion of neurotransmitters could be detected: the urinary glutamate, glutamine, hippurate and tyramine concentrations were significantly lower in the CUMS group. In addition, the urinary concentrations of tryptophan as well as tyrosine were significantly higher in chronically stressed rats. This method allows the assessment of the neurotransmitters associated with CUMS in rat urine in a single analytical run, making it suitable for implementation as a routine technique in depression research. Copyright © 2015 John Wiley & Sons, Ltd.
研究领域:
生物化学
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医学研究
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神经科学
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DOI
PubMed
高影响因子
Pharmacological Reports
·
2019
·Vol. 71
·期 3
·430-437
·
IF 2.761
Zhu Ji-Xiao,Hu Wei-Qiong,Dong Shu-Qi,Yi Li-Tao,Zeng Jin-Xiang,Li Min
Background Perillaldehyde is one of the main components in perilla. Previous studies have shown that perillaldehyde exerted an antidepressant effect in mice, some of which is mediated through regulation of the anti-inflammatory system and the monoamine system. The primary objective of this study was to investigate the possible effects of perillaldehyde on the neurotrophic system and to elucidate whether its antidepressant effect requires brain-derived neurotrophic factor (BDNF) signaling. Methods Mice were exposed to chronic unpredictable mild stress (CUMS) and orally administrated with perillaldehyde for 4 weeks for behavioral testing. Results Perillaldehyde not only reversed the decrease in sucrose preference but also attenuated the increase in feeding latency. In addition, perillaldehyde can attenuate the reduction of CUMS-induced hippocampal BDNF levels. Our further study found that the BDNF receptor tropomyosin receptor kinase B (TrkB) antagonist K252a completely blocked the antidepressant effect of perillaldehyde in mice. Biochemical analysis showed that K252a pretreatment completely prevented the improvement of BDNF, extracellular signal-regulated kinase (ERK) phosphorylation and synaptic protein. Conclusions These results indicated that activation of BDNF-ERK signaling in the hippocampus was required, at least in part for the antidepressant effects of perillaldehyde.
研究领域:
神经科学
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药理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
FITOTERAPIA
·
2023
·
IF 3.4
Bike Zhang,Dan Su,Yonggui Song,Huizhen Li,Changlian Chen,Liangliang Liao,Hongjie Zhang,Jian Luo,Ming Yang,Genhua Zhu,Zhifu Ai
Phytochemical investigation of the volatile oil of Yueju (YJVO) and its constituent herbs induced the detection of 52 compounds in YJVO, mainly monoterpenes and sesquiterpenes as well as a small amount of aromatic and aliphatic compounds. 5 of these compounds were found only in the YJVO instead of the volatile oil of its constituent herbs. The anti-depressant effect of YJVO was proved by behavioral tests in chronic unpredictable mild stress (CUMS) mice. An acute oral toxicity evaluation determined the LD 50 of YJVO was 5.780 mL/kg. Doppler ultrasound and laser speckle imaging have detected that the YJVO could improve depression-related cerebral blood flow. In addition, related neurotransmitters and proteins were analyzed through targeted metabolomics and immunofluorescence. The potential antidepressant mechanisms of YJVO related to significantly decreasing Glu in CUMS mice by up-regulating the ERK/AKT-mediated expression of GLT-1.
研究领域:
药理学
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神经科学
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植物化学
·
行为科学
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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）