Antidepressants are the main drugs used to treat depression,but they have not been shown to be effective in the treatment of child and adolescent depression.However,many adolescent depression treatment guidelines stil...Antidepressants are the main drugs used to treat depression,but they have not been shown to be effective in the treatment of child and adolescent depression.However,many adolescent depression treatment guidelines still recommend the use of antidepressants,especially specific serotonin re-uptake inhibitors.Previous studies have suggested that antidepressants have little therapeutic effect but many side effects,such as switching to mania,suicide,and non-suicidal self injury(NSSI),in the treatment of child and adolescent depression.In the process of developing guidelines,drug recommendations should not only focus on impro-ving symptoms,but they should also consider potential side effects.This review discusses the serious side effects of antidepressants,including switching to mania,suicide,and NSSI.展开更多
Ketamine is recognized for its rapid-onset and longer-term antidepressant actions,but the molecular mechanisms underlying these outcomes are not fully comprehended.Our prior research indicated that the covalent modifi...Ketamine is recognized for its rapid-onset and longer-term antidepressant actions,but the molecular mechanisms underlying these outcomes are not fully comprehended.Our prior research indicated that the covalent modification of ketamine or its metabolites on hippocampus protein may contribute to its antidepressant actions,however,the specific molecular mechanisms are yet to be elucidated.In this research,we employed chemical proteomics approaches to investigate comprehensively the covalent interactions between ketamine or its metabolites and hippocampus proteins in vivo.We discovered that ketamine could covalently bind to lysine residues on proteins after bioactivation,complementing our previous finding of cysteine modification.Moreover,comprehensive chemical proteomics analysis revealed that 21 proteins were modified by ketamine or its metabolites in mouse hippocampus.Finally,bioinformatics analysis revealed that ketamine exerted antidepressant effects via multi-target and multi-pathway mechanism especially involved in synaptic plasticity.These findings offer a novel perspective for understanding the underlying molecular mechanism of antidepressant action.展开更多
Background:The development of ketamine-like rapid antidepressants holds promise for enhancing the therapeutic efficacy of depression,but the underlying cellular and molecular mechanisms remain unclear.Implicated in de...Background:The development of ketamine-like rapid antidepressants holds promise for enhancing the therapeutic efficacy of depression,but the underlying cellular and molecular mechanisms remain unclear.Implicated in depression regulation,the neuropeptide pituitary adenylate cyclase-activating polypeptide(PACAP)is investigated here to examine its role in mediating the rapid antidepressant response.Methods:The onset of antidepressant response was assessed through depression-related behavioral paradigms.The signaling mechanism of PACAP in the hippocampal dentate gyrus(DG)was evaluated by utilizing site-directed gene knockdown,pharmacological interventions,or optogenetic manipulations.Overall,446 mice were used for behavioral and molecular signaling testing.Mice were divided into control or experimental groups randomly in each experiment,and the experimental manipulations included:chronic paroxetine treatments(4 d,9 d,14 d)or a single treatment of ketamine;social defeat or lipopolysaccharides-injection induced depression models;different doses of PACAP(0.4 ng/site,2 ng/site,4 ng/site;microinjected into the hippocampal DG);pharmacological intra-DG interventions(CALM and PACAP6-38);intra-DG viral-mediated PACAP RNAi;and opotogenetics using channelrhodopsins 2(ChR2)or endoplasmic natronomonas halorhodopsine 3.0(eNpHR3.0).Behavioral paradigms included novelty suppressed feeding test,tail suspension test,forced swimming test,and sucrose preference test.Western blotting,ELISA,or quantitative real-time PCR(RT-PCR)analysis were used to detect the expressions of proteins/peptides or genes in the hippocampus.Results:Chronic administration of the slow-onset antidepressant paroxetine resulted in an increase in hippocampal PACAP expression,and intra-DG blockade of PACAP attenuated the onset of the antidepressant response.The levels of hippocampal PACAP expression were reduced in both two distinct depression animal models and intra-DG knockdown of PACAP induced depression-like behaviors.Conversely,a single infusion of PACAP into the DG region produced a rapid and sustained antidepressant response in both normal and chronically stressed mice.Optogenetic intra-DG excitation of PACAP-expressing neurons instantly elicited antidepressant responses,while optogenetic inhibition induced depression-like behaviors.The longer optogenetic excitation/inhibition elicited the more sustained antidepressant/depression-like responses.Intra-DG PACAP infusion immediately facilitated the signaling for rapid antidepressant response by inhibiting calcium/calmodulin-dependent protein kinaseⅡ(CaM KⅡ)-eukaryotic elongation factor 2(eEF2)and activating the mammalian target of rapamycin(mTOR).Pre-activation of CaMKⅡsignaling within the DG blunted PACAP-induced rapid antidepressant response as well as eEF2-mTOR-brain-derived neurotrophic factor(BDNF)signaling.Finally,acute ketamine treatment upregulated hippocampal PACAP expression,whereas intraDG blockade of PACAP signaling attenuated ketamine’s rapid antidepressant response.Conclusions:Activation of hippocampal PACAP signaling induces a rapid antidepressant response through the regulation of CaMKⅡinhibition-governed eEF2-mTOR-BDNF signaling.展开更多
To the editor:Using drugs off-label in paediatric patients(age:0-18 years)has drawn increasing attention worldwide.Off-label use of drugs implies using drugs beyond the scope of their approved market authorisation(eg,...To the editor:Using drugs off-label in paediatric patients(age:0-18 years)has drawn increasing attention worldwide.Off-label use of drugs implies using drugs beyond the scope of their approved market authorisation(eg,patient age,indication,dosage and route of administration).Previous literature reported that the prevalence of off-label drug use ranged from36.3%to 97.0%among paediatric patients worldwide.展开更多
To the editor:A wide range of affective disorders affects people of all ages globally and contributes significantly to the global disease burden.1 In China,a nationwide survey found a 3.21% prevalence of affective dis...To the editor:A wide range of affective disorders affects people of all ages globally and contributes significantly to the global disease burden.1 In China,a nationwide survey found a 3.21% prevalence of affective disorders in children and adolescents,with major depressive disorder(MDD)at 2.00%and bipolar disorder at 0.86%.展开更多
目的分析近十年老年抑郁领域的国内外研究进展,以期为未来老年抑郁研究提供参考。方法分别检索CNKI数据库与Web of Science核心合集2015年1月1日—2024年8月25日发表的老年抑郁相关中英文文献,运用CiteSpace、VOSviewer软件,通过作者与...目的分析近十年老年抑郁领域的国内外研究进展,以期为未来老年抑郁研究提供参考。方法分别检索CNKI数据库与Web of Science核心合集2015年1月1日—2024年8月25日发表的老年抑郁相关中英文文献,运用CiteSpace、VOSviewer软件,通过作者与机构合作网络、关键词共现网络、聚类分析、爆发词分析等方法进行文献计量学分析,并对中英文文献进行对比。结果共纳入495篇中文文献与4446篇英文文献。中文文献发文量波动小、数量少,英文文献年发文量呈缓慢上升趋势。中英文领域均形成核心作者团队与合作网络,且英文文献广度与深度更优。社会支持、药物治疗、焦虑是二者共同的热点话题,中文文献侧重特殊人群与社会因素,英文文献形成了流行病学特征、认知损害关联、危险因素、焦虑共病与干预手段等聚类。高被引文献中文以流行病学研究为主,英文多为综述与指南类。结论近十年老年抑郁领域已形成丰富的研究积累,但老年患者的特殊社会与生理特点以及更合理的治疗手段仍需进一步探讨。中文文献尚处起步阶段,需提升关注程度与体系化水平,丰富新型药物临床证据;英文文献稳步发展,需加强专属老年抑郁人群的研究。展开更多
Perilla frutescens(Perilla leaf), a garnishing vegetable in East Asian countries, as well as a plant-based medicine, has been used for centuries to treat various conditions, including depression. Several studies have ...Perilla frutescens(Perilla leaf), a garnishing vegetable in East Asian countries, as well as a plant-based medicine, has been used for centuries to treat various conditions, including depression. Several studies have demonstrated that the essential oil of P. frutescens(EOPF) attenuated the depressive-like behavior in mice. The present study was designed to test the anti-depressant effects of EOPF and the possible mechanisms in an chronic, unpredictable, mild stress(CUMS)-induced mouse model. With the exposure to stressor once daily for five consecutive weeks, EOPF(3, 6, and 9 mg·kg-1) and a positive control drug fluoxetine(20 mg·kg-1) were administered through gastric intubation to mice once daily for three consecutive weeks from the 3rd week. Open-field test, sucrose consumption test, tail suspension test(TST), and forced swimming test(FST) were used to evaluate the behavioral activity. The contents of 5-hydroxytryptamine(5-HT) and its metabolite, 5-hydroxyindoleacetic acid(5-HIAA), in mouse hippocampus were determined by HPLC–ECD. Serum interleukin(IL)-1, IL-6, and tumor necrosis factor(TNF)-α levels were evaluated by enzyme-linked immunosorbent assay(ELISA). The results showed that CUMS significantly decreased the levels of 5-HT and 5-HIAA in the hippocampus, with an increase in plasma IL-6, IL-1β, and TNF-α levels. CUMS also reduced open-field activity, sucrose consumption, as well as increased immobility duration in FST and TST. EOPF administration could effectively reverse the alterations in the concentrations of 5-HT and 5-HIAA; reduce the IL-6, IL-1β, and TNF-α levels. Moreover, EOPF could effectively reverse alterations in immobility duration, sucrose consumption, and open-field activity. However, the effect was not dose-dependent. In conclusion, EOPF administration exhibited significant antidepressant-like effects in mice with CUMS-induced depression. The antidepressant activity of EOPF might be related to the relation between alteration of serotonergic responses and anti-inflammatory effects.展开更多
We aimed to evaluate the efficacy of tricyclic antidepressants(TCAs) as a therapeutic option for irritable bowel syndrome(IBS) through meta-analysis of randomized controlled trials.For the years 1966 until September 2...We aimed to evaluate the efficacy of tricyclic antidepressants(TCAs) as a therapeutic option for irritable bowel syndrome(IBS) through meta-analysis of randomized controlled trials.For the years 1966 until September 2008,PubMed,Scopus,Web of Science,and Cochrane Central Register of Controlled Trials were searched for double-blind,placebo-controlled trials investigating the effi cacy of TCAs in the management of IBS.Seven randomized,placebo-controlled clinical trials met our criteria and were included in the metaanalysis.TCAs used in the treatment arm of these trials included amitriptyline,imipramine,desipramine,doxepin and trimipramine.The pooled relative risk for clinical improvement with TCA therapy was 1.93(95% CI:1.44 to 2.6,P<0.0001).Effect size of TCAs versus placebo for mean change in abdominal pain score among the two studies was -44.15(95% CI:-53.27 to -35.04,P<0.0001).It is concluded that low dose TCAs exhibit clinically and statistically signifi cant control of IBS symptoms.展开更多
OBJECTIVE: To identify the antidepressant effect of Xingnao Jieyu (XNJY) decoction on a post-stroke depression (PSD) rat model and the underlying molecular mechanism. METHODS: We established a rat PSD model by middle ...OBJECTIVE: To identify the antidepressant effect of Xingnao Jieyu (XNJY) decoction on a post-stroke depression (PSD) rat model and the underlying molecular mechanism. METHODS: We established a rat PSD model by middle cerebral artery occlusion (MCAO) combined with chronic unpredictable mild stress (CUMS). Healthy SD rats were randomly divided into six groups: sham, PSD, fluoxetine (Flu), and XNJY groups at low, middle, and high doses. The sham group underwent sham operation, while the other groups underwent MCAO+CUMS. The Flu and XNJY decoction groups were intragastrically administered with Flu or different doses of XNJY for 21 consecutive days. Histopathological changes in the cortex and hippocampus were observed by staining with hematoxylin and eosin and Terminal-deoxynucleoitidyl Transferase Mediated Nick End Labeling. Iba1 positive cells were evaluated by immunofluorescence assay. The expressions of tumor necrosis factor-α(TNF-α), interleukin-6 (IL-6), interleukin-1β(IL-1β), 5-hydroxytryptamine (5-HT), and norepinephrine (NE) in the cortex and hippocampus were measured by enzyme linked immunosorbent assay. RESULTS: The PSD group rats had a significant decrease in body weight, consumption of sucrose water, and locomotor activity but an increase in immobility time during a forced swimming test (P < 0.01) compared with sham group. Flu and different doses of XNJY significantly recovered these indices (P < 0.01). XNJY also inhibited neuronal damage and apoptosis in the cortex induced by PSD (P < 0.01). Furthermore, XNJY reduced the number of Iba1 positive cells and the expressions of TNF-α, IL-6, and IL-1β, in addition to recovered the levels of 5-HT and NE in the cortex and hippocampus (P < 0.01). CONCLUSION: The alleviation of neuroinflammation might be an important mechanism of the XNJY decoction against PSD. Thus, XNJY might be a promising candidate for the treatment of PSD.展开更多
Albiziae Flos(AF)has been experimentally proven to have an antidepressant effect.However,due to the complexity of botanical ingredients,the exact pharmacological mechanism of action of AF in depression has not been co...Albiziae Flos(AF)has been experimentally proven to have an antidepressant effect.However,due to the complexity of botanical ingredients,the exact pharmacological mechanism of action of AF in depression has not been completely deciphered.This study used the network pharmacology method to construct a component-target-pathway network to explore the active components and potential mechanisms of action of AF.The methods included collection and screening of chemical components,prediction of depression-associated targets of the active components,gene enrichment,and network construction and analysis.Quercetin and 4 other active components were found to exert an tidepressant effects mainly via monoaminergic neurotransmitters and cAMP signaling and neuroactive ligand・wceptor interaction pathways.DRD2,HTR1 A,and SLC6A4 were identified as important targets of the studied bioactive components of AF.This network pharmacology analysis provides guidance for further study of the antidepressant mechanism of AF.展开更多
文摘Antidepressants are the main drugs used to treat depression,but they have not been shown to be effective in the treatment of child and adolescent depression.However,many adolescent depression treatment guidelines still recommend the use of antidepressants,especially specific serotonin re-uptake inhibitors.Previous studies have suggested that antidepressants have little therapeutic effect but many side effects,such as switching to mania,suicide,and non-suicidal self injury(NSSI),in the treatment of child and adolescent depression.In the process of developing guidelines,drug recommendations should not only focus on impro-ving symptoms,but they should also consider potential side effects.This review discusses the serious side effects of antidepressants,including switching to mania,suicide,and NSSI.
基金supported by the Science and Technology Development Fund,Macao SAR(File no.0001/2020/AKP and 006/2023/SKL)the Youth Fund Project of National Natural Science Foundation of China(Grant No.22406065)。
文摘Ketamine is recognized for its rapid-onset and longer-term antidepressant actions,but the molecular mechanisms underlying these outcomes are not fully comprehended.Our prior research indicated that the covalent modification of ketamine or its metabolites on hippocampus protein may contribute to its antidepressant actions,however,the specific molecular mechanisms are yet to be elucidated.In this research,we employed chemical proteomics approaches to investigate comprehensively the covalent interactions between ketamine or its metabolites and hippocampus proteins in vivo.We discovered that ketamine could covalently bind to lysine residues on proteins after bioactivation,complementing our previous finding of cysteine modification.Moreover,comprehensive chemical proteomics analysis revealed that 21 proteins were modified by ketamine or its metabolites in mouse hippocampus.Finally,bioinformatics analysis revealed that ketamine exerted antidepressant effects via multi-target and multi-pathway mechanism especially involved in synaptic plasticity.These findings offer a novel perspective for understanding the underlying molecular mechanism of antidepressant action.
基金supported by the National Key Research and Development Program of China(2022YFE0201000)the National Natural Science Foundation of China(82174002,82104416,82204652)the High-Level University Development Program of Guangdong Province,and the Guangzhou Key Science and Technology Research and Development Project(202206010109)。
文摘Background:The development of ketamine-like rapid antidepressants holds promise for enhancing the therapeutic efficacy of depression,but the underlying cellular and molecular mechanisms remain unclear.Implicated in depression regulation,the neuropeptide pituitary adenylate cyclase-activating polypeptide(PACAP)is investigated here to examine its role in mediating the rapid antidepressant response.Methods:The onset of antidepressant response was assessed through depression-related behavioral paradigms.The signaling mechanism of PACAP in the hippocampal dentate gyrus(DG)was evaluated by utilizing site-directed gene knockdown,pharmacological interventions,or optogenetic manipulations.Overall,446 mice were used for behavioral and molecular signaling testing.Mice were divided into control or experimental groups randomly in each experiment,and the experimental manipulations included:chronic paroxetine treatments(4 d,9 d,14 d)or a single treatment of ketamine;social defeat or lipopolysaccharides-injection induced depression models;different doses of PACAP(0.4 ng/site,2 ng/site,4 ng/site;microinjected into the hippocampal DG);pharmacological intra-DG interventions(CALM and PACAP6-38);intra-DG viral-mediated PACAP RNAi;and opotogenetics using channelrhodopsins 2(ChR2)or endoplasmic natronomonas halorhodopsine 3.0(eNpHR3.0).Behavioral paradigms included novelty suppressed feeding test,tail suspension test,forced swimming test,and sucrose preference test.Western blotting,ELISA,or quantitative real-time PCR(RT-PCR)analysis were used to detect the expressions of proteins/peptides or genes in the hippocampus.Results:Chronic administration of the slow-onset antidepressant paroxetine resulted in an increase in hippocampal PACAP expression,and intra-DG blockade of PACAP attenuated the onset of the antidepressant response.The levels of hippocampal PACAP expression were reduced in both two distinct depression animal models and intra-DG knockdown of PACAP induced depression-like behaviors.Conversely,a single infusion of PACAP into the DG region produced a rapid and sustained antidepressant response in both normal and chronically stressed mice.Optogenetic intra-DG excitation of PACAP-expressing neurons instantly elicited antidepressant responses,while optogenetic inhibition induced depression-like behaviors.The longer optogenetic excitation/inhibition elicited the more sustained antidepressant/depression-like responses.Intra-DG PACAP infusion immediately facilitated the signaling for rapid antidepressant response by inhibiting calcium/calmodulin-dependent protein kinaseⅡ(CaM KⅡ)-eukaryotic elongation factor 2(eEF2)and activating the mammalian target of rapamycin(mTOR).Pre-activation of CaMKⅡsignaling within the DG blunted PACAP-induced rapid antidepressant response as well as eEF2-mTOR-brain-derived neurotrophic factor(BDNF)signaling.Finally,acute ketamine treatment upregulated hippocampal PACAP expression,whereas intraDG blockade of PACAP signaling attenuated ketamine’s rapid antidepressant response.Conclusions:Activation of hippocampal PACAP signaling induces a rapid antidepressant response through the regulation of CaMKⅡinhibition-governed eEF2-mTOR-BDNF signaling.
基金supported by the National Natural Science Foundation of China (No.72374011).
文摘To the editor:Using drugs off-label in paediatric patients(age:0-18 years)has drawn increasing attention worldwide.Off-label use of drugs implies using drugs beyond the scope of their approved market authorisation(eg,patient age,indication,dosage and route of administration).Previous literature reported that the prevalence of off-label drug use ranged from36.3%to 97.0%among paediatric patients worldwide.
基金the Tianjin Health Research Project(Grant No.TJWJ2023MS038)Tianjin Education Commission Research Project(Grant No.2023KJ044)S&T Program of Hebei(SG2021189)。
文摘To the editor:A wide range of affective disorders affects people of all ages globally and contributes significantly to the global disease burden.1 In China,a nationwide survey found a 3.21% prevalence of affective disorders in children and adolescents,with major depressive disorder(MDD)at 2.00%and bipolar disorder at 0.86%.
文摘目的分析近十年老年抑郁领域的国内外研究进展,以期为未来老年抑郁研究提供参考。方法分别检索CNKI数据库与Web of Science核心合集2015年1月1日—2024年8月25日发表的老年抑郁相关中英文文献,运用CiteSpace、VOSviewer软件,通过作者与机构合作网络、关键词共现网络、聚类分析、爆发词分析等方法进行文献计量学分析,并对中英文文献进行对比。结果共纳入495篇中文文献与4446篇英文文献。中文文献发文量波动小、数量少,英文文献年发文量呈缓慢上升趋势。中英文领域均形成核心作者团队与合作网络,且英文文献广度与深度更优。社会支持、药物治疗、焦虑是二者共同的热点话题,中文文献侧重特殊人群与社会因素,英文文献形成了流行病学特征、认知损害关联、危险因素、焦虑共病与干预手段等聚类。高被引文献中文以流行病学研究为主,英文多为综述与指南类。结论近十年老年抑郁领域已形成丰富的研究积累,但老年患者的特殊社会与生理特点以及更合理的治疗手段仍需进一步探讨。中文文献尚处起步阶段,需提升关注程度与体系化水平,丰富新型药物临床证据;英文文献稳步发展,需加强专属老年抑郁人群的研究。
基金supported by the Priority Academic Program Development of Jiangsu Higher Education Institutionsthe Natural Science Foundation of Jiangsu Province of China(No.BK2011630)
文摘Perilla frutescens(Perilla leaf), a garnishing vegetable in East Asian countries, as well as a plant-based medicine, has been used for centuries to treat various conditions, including depression. Several studies have demonstrated that the essential oil of P. frutescens(EOPF) attenuated the depressive-like behavior in mice. The present study was designed to test the anti-depressant effects of EOPF and the possible mechanisms in an chronic, unpredictable, mild stress(CUMS)-induced mouse model. With the exposure to stressor once daily for five consecutive weeks, EOPF(3, 6, and 9 mg·kg-1) and a positive control drug fluoxetine(20 mg·kg-1) were administered through gastric intubation to mice once daily for three consecutive weeks from the 3rd week. Open-field test, sucrose consumption test, tail suspension test(TST), and forced swimming test(FST) were used to evaluate the behavioral activity. The contents of 5-hydroxytryptamine(5-HT) and its metabolite, 5-hydroxyindoleacetic acid(5-HIAA), in mouse hippocampus were determined by HPLC–ECD. Serum interleukin(IL)-1, IL-6, and tumor necrosis factor(TNF)-α levels were evaluated by enzyme-linked immunosorbent assay(ELISA). The results showed that CUMS significantly decreased the levels of 5-HT and 5-HIAA in the hippocampus, with an increase in plasma IL-6, IL-1β, and TNF-α levels. CUMS also reduced open-field activity, sucrose consumption, as well as increased immobility duration in FST and TST. EOPF administration could effectively reverse the alterations in the concentrations of 5-HT and 5-HIAA; reduce the IL-6, IL-1β, and TNF-α levels. Moreover, EOPF could effectively reverse alterations in immobility duration, sucrose consumption, and open-field activity. However, the effect was not dose-dependent. In conclusion, EOPF administration exhibited significant antidepressant-like effects in mice with CUMS-induced depression. The antidepressant activity of EOPF might be related to the relation between alteration of serotonergic responses and anti-inflammatory effects.
基金Supported by National Science Foundation, Tehran
文摘We aimed to evaluate the efficacy of tricyclic antidepressants(TCAs) as a therapeutic option for irritable bowel syndrome(IBS) through meta-analysis of randomized controlled trials.For the years 1966 until September 2008,PubMed,Scopus,Web of Science,and Cochrane Central Register of Controlled Trials were searched for double-blind,placebo-controlled trials investigating the effi cacy of TCAs in the management of IBS.Seven randomized,placebo-controlled clinical trials met our criteria and were included in the metaanalysis.TCAs used in the treatment arm of these trials included amitriptyline,imipramine,desipramine,doxepin and trimipramine.The pooled relative risk for clinical improvement with TCA therapy was 1.93(95% CI:1.44 to 2.6,P<0.0001).Effect size of TCAs versus placebo for mean change in abdominal pain score among the two studies was -44.15(95% CI:-53.27 to -35.04,P<0.0001).It is concluded that low dose TCAs exhibit clinically and statistically signifi cant control of IBS symptoms.
基金Supported by the Natural Science Foundation of China:Study on the mechanism of eliminating phlegm and dissolving blood stasis interfering cAMP-response element binding protein signal pathway in post-stroke depression treatment(No.81373840)
文摘OBJECTIVE: To identify the antidepressant effect of Xingnao Jieyu (XNJY) decoction on a post-stroke depression (PSD) rat model and the underlying molecular mechanism. METHODS: We established a rat PSD model by middle cerebral artery occlusion (MCAO) combined with chronic unpredictable mild stress (CUMS). Healthy SD rats were randomly divided into six groups: sham, PSD, fluoxetine (Flu), and XNJY groups at low, middle, and high doses. The sham group underwent sham operation, while the other groups underwent MCAO+CUMS. The Flu and XNJY decoction groups were intragastrically administered with Flu or different doses of XNJY for 21 consecutive days. Histopathological changes in the cortex and hippocampus were observed by staining with hematoxylin and eosin and Terminal-deoxynucleoitidyl Transferase Mediated Nick End Labeling. Iba1 positive cells were evaluated by immunofluorescence assay. The expressions of tumor necrosis factor-α(TNF-α), interleukin-6 (IL-6), interleukin-1β(IL-1β), 5-hydroxytryptamine (5-HT), and norepinephrine (NE) in the cortex and hippocampus were measured by enzyme linked immunosorbent assay. RESULTS: The PSD group rats had a significant decrease in body weight, consumption of sucrose water, and locomotor activity but an increase in immobility time during a forced swimming test (P < 0.01) compared with sham group. Flu and different doses of XNJY significantly recovered these indices (P < 0.01). XNJY also inhibited neuronal damage and apoptosis in the cortex induced by PSD (P < 0.01). Furthermore, XNJY reduced the number of Iba1 positive cells and the expressions of TNF-α, IL-6, and IL-1β, in addition to recovered the levels of 5-HT and NE in the cortex and hippocampus (P < 0.01). CONCLUSION: The alleviation of neuroinflammation might be an important mechanism of the XNJY decoction against PSD. Thus, XNJY might be a promising candidate for the treatment of PSD.
基金the National Natural Science Foundation of China(No.31570343).
文摘Albiziae Flos(AF)has been experimentally proven to have an antidepressant effect.However,due to the complexity of botanical ingredients,the exact pharmacological mechanism of action of AF in depression has not been completely deciphered.This study used the network pharmacology method to construct a component-target-pathway network to explore the active components and potential mechanisms of action of AF.The methods included collection and screening of chemical components,prediction of depression-associated targets of the active components,gene enrichment,and network construction and analysis.Quercetin and 4 other active components were found to exert an tidepressant effects mainly via monoaminergic neurotransmitters and cAMP signaling and neuroactive ligand・wceptor interaction pathways.DRD2,HTR1 A,and SLC6A4 were identified as important targets of the studied bioactive components of AF.This network pharmacology analysis provides guidance for further study of the antidepressant mechanism of AF.
