Aim The study focused on identification and antidepression active verification of constituents from An- gelica Sinensis Radix contrubuting to Xiaoyaosan based on UPLC-PDA guided isolation technique. Methods The UPLC-P...Aim The study focused on identification and antidepression active verification of constituents from An- gelica Sinensis Radix contrubuting to Xiaoyaosan based on UPLC-PDA guided isolation technique. Methods The UPLC-PDA chromatogram of Xiaoyaosan was compared with that of Angelica Sinensis Radix. The relative retention time of each peak and the Uhraviolet spectra providing by PDA were used in the analyses. Constituents were isola- ted from Angelica Sinensis Radix under the guidance of UPLC-PDA investigation. Structures of the isolates were elu- cidated by NMR techniques. Anti-depression effect was evaluated on glutamate-induced neurons. Results Five marker peaks of Xiaoyaosan fingerprint were belong to Angelica Sinensis Radix, and they were determined as conife- ryl ferulate（ I）, E-butylidenephthalide （ II）, ligustilide （III）, Z-butylidenephthalide （ IV ）, 14-Acetoxy-12-sene- cioyloxytetradeca-2E,8E,10E-trien-4,6-diyn-l-ol（V）. Compound V was isolated from the plants of Umbelliferae for the first time. Treatment with compound I, III, IV can protect PC12 and SH-SY5Y cell from glutamate-induced cytotoxicity. Antidepression bioactivity of compound I was first investigated. Conclusion UPLC-PDA guided iso-lation technique was confirmed to be a rapid and accurate method to identify the main active constituents from An- gelica Sinensis Radix contrubuting to Xiaoyaosan.展开更多
Traumatic brain injury involves complex pathophysiological mechanisms,among which oxidative stress significantly contributes to the occurrence of secondary injury.In this study,we evaluated hypidone hydrochloride(YL-0...Traumatic brain injury involves complex pathophysiological mechanisms,among which oxidative stress significantly contributes to the occurrence of secondary injury.In this study,we evaluated hypidone hydrochloride(YL-0919),a self-developed antidepressant with selective sigma-1 receptor agonist properties,and its associated mechanisms and targets in traumatic brain injury.Behavioral experiments to assess functional deficits were followed by assessment of neuronal damage through histological analyses and examination of blood-brain barrier permeability and brain edema.Next,we investigated the antioxidative effects of YL-0919 by assessing the levels of traditional markers of oxidative stress in vivo in mice and in vitro in HT22 cells.Finally,the targeted action of YL-0919 was verified by employing a sigma-1 receptor antagonist(BD-1047).Our findings demonstrated that YL-0919 markedly improved deficits in motor function and spatial cognition on day 3 post traumatic brain injury,while also decreasing neuronal mortality and reversing blood-brain barrier disruption and brain edema.Furthermore,YL-0919 effectively combated oxidative stress both in vivo and in vitro.The protective effects of YL-0919 were partially inhibited by BD-1047.These results indicated that YL-0919 relieved impairments in motor and spatial cognition by restraining oxidative stress,a neuroprotective effect that was partially reversed by the sigma-1 receptor antagonist BD-1047.YL-0919 may have potential as a new treatment for traumatic brain injury.展开更多
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
Aripiprazole(ARI),a second-generation atypical antipsychotic drug approved for schizophrenia treatment,shows good efficacy against depression.However,the poorly aqueous solubility of ARI leads to low bioavailability a...Aripiprazole(ARI),a second-generation atypical antipsychotic drug approved for schizophrenia treatment,shows good efficacy against depression.However,the poorly aqueous solubility of ARI leads to low bioavailability and increased dose-related side effects,seriously limiting its application in pharmaceutics.Herein,we demonstrated the fabrication of ARI and poly(methyl vinyl etherco-maleic anhydride)(PVMMA)composite nanoparticles(PA NPs)using the supercritical antisolvent(SAS)process for enhancing its water-solubility and curative anti-depressant effects.Initially,the optimal experimental conditions(ARI/PVMMA mass ratio of 1:6,pressure of 10MPa,and solution flow rate of 0.75ml min^(-1))were determined by a 23 factorial experimental design,resulting in the PA NPs with an excellent particle morphology.In vitro cell experiments showed that PA NPs significantly inhibited the inflammatory response caused by the microglia activation induced by lipopolysaccharide(LPS).Similarly,mice behavioral tests demonstrated that PA NPs significantly improved LPS-induced depression-like behavior.Importantly,compared with free ARI,the LPS-induced activation of microglia in the mouse brain and the expression of inflammatory factors in serum were significantly reduced after treatment with PA NPs.Together,the innovative PA NPs designed by SAS processmight provide a candidate for developing new ARI-based nano-formulations.展开更多
BACKGROUND Traumatic brain injury(TBI)poses a considerable risk to human health.After TBI,individuals are susceptible to a range of psychiatric disorders,with depression being a primary complication.Selective serotoni...BACKGROUND Traumatic brain injury(TBI)poses a considerable risk to human health.After TBI,individuals are susceptible to a range of psychiatric disorders,with depression being a primary complication.Selective serotonin reuptake inhibitors(SSRIs)are frequently used in the treatment of depression;however,their efficacy in addressing major depressive disorder(MDD)in adults following TBI remains uncertain.AIM To investigate the efficacy of SSRIs in the treatment of MDD after TBI.METHODS A comprehensive search across multiple databases was conducted following the guidelines outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement,encompassing studies published until May 2024.This review focused on studies that examined the efficacy of SSRIs in the treatment of MDD following TBI.Studies were assessed based sample size,treatment duration,treatment methodologies,severity of brain injury,assessment techniques,and drug response.A random-effects model was used to derive the summary effect size.RESULTS Eight studies compared the reduction in depression scores in patients with MDD after TBI and SSRI treatment.The eight studies did not exhibit heterogeneity(I^(2)=38%).The depression score for MDD after TBI in the SSRI group decreased more than that in the control group[odds ratio(OR)1.68,95%CI:1.09-2.58,P=0.02].The adverse reactions after treatment included diarrhea,dizziness,dry mouth,nausea,or vomiting.There was no difference in the incidence of adverse reactions after treatment between the two groups(OR 1.16,95%CI:0.78-1.73,P=0.46).These studies did not show significant heterogeneity(I^(2)=44%).CONCLUSION SSRIs may be effective in treating patients with MDD after TBI.Adequately powered,randomized,controlled trials are required to confirm these findings.展开更多
Agitation is a neuropsychiatric syndrome characterized by excessive motor and/or verbal behaviors,with or without aggressive behaviors.The prevalence of agitation in Alzheimer’s disease varies from 5%to over 50%.Mult...Agitation is a neuropsychiatric syndrome characterized by excessive motor and/or verbal behaviors,with or without aggressive behaviors.The prevalence of agitation in Alzheimer’s disease varies from 5%to over 50%.Multiple factors have been implicated in its pathophysiology,including disease stage,comorbidity with other symptoms(e.g.,psychosis,anxiety/depression),and psychosocial factors.Ruling out delirium and identifying environmental triggers are fundamental steps in the management of agitation in Alzheimer’s disease.For establishing an effective therapeutic plan,it is important to define duration,severity,and potential for harm.While non-pharmacological approaches are considered the first line of intervention,pharmacological agents are frequently used in the treatment of agitation.Antipsychotics are commonly used in acute agitation.For chronic agitation,serotonin-selective reuptake inhibitors,especially citalopram and escitalopram,are often preferred due to safety concerns associated with the longterm use of antipsychotics.Promising novel strategies,such as new compounds and neuromodulation,are likely to be incorporated into agitation therapeutics in the next few years.展开更多
[Objectives]This study was conducted to perform visual analysis of the research hotspots and development trends of Cyperi Rhizoma in the field of antidepressant based on CiteSpace,so as to explore the application and ...[Objectives]This study was conducted to perform visual analysis of the research hotspots and development trends of Cyperi Rhizoma in the field of antidepressant based on CiteSpace,so as to explore the application and development direction of Cyperi Rhizoma in the field of antidepressant.[Methods]Highly-relevant literatures were selected from the core database of China National Knowledge Infrastructure(CNKI),and CiteSpace and WPS office software were employed to visually analyze relevant contents such as publishing institutions,scholars,keywords,publishing time,and citation frequency.[Results]A total of 297 domestic relevant literatures were selected.Most of the publications,institutions and authors were concentrated in universities,affiliated institutions and scientific research institutes of traditional Chinese medicine in China,and no relatively novel applied research direction has emerged.At present,the hot spots and frontiers of application were mostly concentrated in its role in treating depression,anxiety,gynecological diseases and other disorders.[Conclusions]The research on Cyperi Rhizoma for its antidepressant effects in China originated in the late 20 th century.From 2004 to 2024,studies have primarily focused on its pharmacological principles,mechanisms of action,and classification,while the exploration of its application in specific depressive disorders was limited.Overall,research progress has been relatively slow.Currently,further efforts are needed to optimize the active antidepressant components of Cyperi Rhizoma and clarify its mechanisms of action,which will facilitate its broader application in treating various stages of depressive disorders.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
A recent meta-analysis has suggested a 5-HTR1A promoter variant may predict antidepressant response.The present review comments on the claims made in view of sensitivity issues and issues pertaining to genetic exposur...A recent meta-analysis has suggested a 5-HTR1A promoter variant may predict antidepressant response.The present review comments on the claims made in view of sensitivity issues and issues pertaining to genetic exposure.We also alert to errors in the original data that had been carried over.Specifically,primers meant to amplify the HTR1A gene aligned to the BDNF gene sequence.Alleles had been confounded owing to DNA strand ambiguities and demographic information proved inaccurate.In the light of these findings,adherence to PRISMA guidelines and use of the Newcastle-Ottawa Scale did not safeguard against bias.More after action reviews are encouraged to identify factors likely to interfere with estimates of genetic risk in large data sets.These may result from pooling of ethnic groups,the use of binary data or other formats that are not human-readable,the introduction of surrogate identifiers and a failure to reverseengineer previously published experimental protocols.Unless the above challenges are met,sequence variants are unlikely to inform personalized medicine strategies in psychiatry.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
Although antipsychotics that act via monoaminergic neurotransmitter modulation have considera ble therapeutic effect,they cannot completely relieve clinical symptoms in patients suffering from psychiatric disorde rs.T...Although antipsychotics that act via monoaminergic neurotransmitter modulation have considera ble therapeutic effect,they cannot completely relieve clinical symptoms in patients suffering from psychiatric disorde rs.This may be attributed to the limited range of neurotransmitters that are regulated by psychotropic drugs.Recent findings indicate the need for investigation of psychotropic medications that target less-studied neurotransmitte rs.Among these candidate neurotransmitters,lactate is developing from being a waste metabolite to a glial-neuronal signaling molecule in recent years.Previous studies have suggested that cerebral lactate levels change considerably in numerous psychiatric illnesses;animal experiments have also shown that the supply of exogenous la ctate exerts an antidepressant effect.In this review,we have described how medications targeting newer neurotransmitte rs offer promise in psychiatric diseases;we have also summarized the advances in the use of lactate(and its corresponding signaling pathways)as a signaling molecule.In addition,we have described the alterations in brain lactate levels in depression,anxiety,bipolar disorder,and schizophrenia and have indicated the challenges that need to be overcome before brain lactate can be used as a therapeutic target in psychopharmacology.展开更多
Globally,the prevalence of anxiety and depression has reached epidemic proportions.Food-derived protein hydrolysates and peptides delivered through dietary supplementation can avoid the negative risks associated with ...Globally,the prevalence of anxiety and depression has reached epidemic proportions.Food-derived protein hydrolysates and peptides delivered through dietary supplementation can avoid the negative risks associated with traditional pharmaceuticals while delivering superior anxiolytic and antidepressant effects.This review summarizes current research on food-derived anxiolytic and antidepressant protein hydrolysates and peptides,and subsequently analyses their physicochemical characteristics and elaborates on their mechanisms.The aim of this work is to contribute to the in-depth study and provide a theoretical foundation for the development of related products to better serve patients with anxiety and depression.展开更多
γ-Aminobutyric acid(GABA) neurotransmission alterations have been implicated to play a role in depression pathogenesis. While GABA_(A) receptor positive allosteric modulators are emerging as promising in clinical pra...γ-Aminobutyric acid(GABA) neurotransmission alterations have been implicated to play a role in depression pathogenesis. While GABA_(A) receptor positive allosteric modulators are emerging as promising in clinical practice, their precise antidepressant mechanism remains to be further elucidated. The aim of the present study was to investigate the effects of LY-02, a novel compound derived from the metabolite of timosaponin, on depression in animals and its mechanism. The results of behavioral tests showed that LY-02 exhibited better antidepressant effects in both male C57BL/6 mice and Sprague Dawley(SD) rats. The results of cellular voltage clamp experiments showed that LY-02 enhanced GABA-mediated currents in HEK293T cells expressing recombinant α6β3δ subunitcontaining GABA_(A) receptors. Electrophysiological recording from brain slices showed that LY-02 decreased the amplitude of spontaneous inhibitory postsynaptic current(sIPSC) and increased action potentials of pyramidal neurons in the medial prefrontal cortex(mPFC) of C57BL/6 mice. Western blot results showed that LY-02 dose-dependently up-regulated the protein expression levels of brain-derived neurotrophic factor(BDNF), tropomyosin related kinase B(TrkB) and postsynaptic density protein 95(PSD-95) in m PFC of mice. The above results suggest that LY-02, as a positive modulator of GABA_(A) receptors, reduces inhibitory neurotransmission in pyramidal neurons. It further activates the BDNF/TrkB signaling pathway, thus exerting antidepressant effects. It suggests that LY-02 is a potential novel therapeutic agent for depression treatment.展开更多
BACKGROUND Major depressive disorder(MDD)is a substantial global health concern,and its treatment is complicated by the variability in individual response to antide-pressants.AIM To consolidate research and clarify th...BACKGROUND Major depressive disorder(MDD)is a substantial global health concern,and its treatment is complicated by the variability in individual response to antide-pressants.AIM To consolidate research and clarify the impact of genetic variation on MDD treatment outcomes.METHODS Adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines,a systematic search across PubMed,EMBASE,Web of Science,and the Cochrane Library was conducted without date restrictions,utilizing key terms related to MDD,serotonin 1A receptor polymorphism(5-HTR1A),C-1019G polymorphism,and antidepressant response.Studies meeting inclusion criteria were thoroughly screened,and quality assessed using the Newcastle-Ottawa Scale.Statistical analyses,includingχ2 and I²values,were used to evaluate heterogeneity and fixed-effect or random-effect models were applied accordingly.RESULTS The initial search yielded 1216 articles,with 11 studies meeting criteria for inclusion.Analysis of various genetic models showed no significant association between the 5-HTR1A C-1019G polymorphism and antidepressant efficacy.The heterogeneity was low to moderate,and no publication bias was detected through funnel plot symmetry and Egger's and Begg's tests.CONCLUSION This meta-analysis does not support a significant association between the 5-HTR1A C-1019G polymorphism and the efficacy of antidepressant treatment in MDD.The findings call for further research with larger cohorts to substantiate these results and enhance the understanding of antidepressant pharmacogenetics.展开更多
It has been reported both in clinic and rodent models that beyond spinal cord injury directly induced symptoms, such as paralysis, neuropathic pain, bladder/bowel dysfunction, and loss of sexual function, there are a ...It has been reported both in clinic and rodent models that beyond spinal cord injury directly induced symptoms, such as paralysis, neuropathic pain, bladder/bowel dysfunction, and loss of sexual function, there are a variety of secondary complications, including memory loss, cognitive decline, depression, and Alzheimer's disease. The largescale longitudinal population-based studies indicate that post-trauma depression is highly prevalent in spinal cord injury patients. Yet, few basic studies have been conducted to address the potential molecular mechanisms. One of possible factors underlying the depression is the reduction of adult hippocampal neurogenesis which may come from less physical activity, social isolation, chronic pain, and elevated neuroinflammation after spinal cord injury. However, there is no clear consensus yet. In this review, we will first summarize the alteration of hippocampal neurogenesis post-spinal cord injury. Then, we will discuss possible mechanisms underlie this important spinal cord injury consequence. Finally, we will outline the potential therapeutic options aimed at enhancing hippocampal neurogenesis to ameliorate depression.展开更多
Depression can be counted as the most severe mental disease in the world nowadays, which lacks effective curing treatments. With an increasing number of patients, developing effective treatments with fewer side effect...Depression can be counted as the most severe mental disease in the world nowadays, which lacks effective curing treatments. With an increasing number of patients, developing effective treatments with fewer side effects is essential. Medicinal food homology has been proven to influence the pathogenesis of depression positively. Gut microbiota plays a vital role in exerting the antidepressant effect of substances from the medicinal food homology, as they facilitate different chemical processes and increase the bioavailability of the substances. This review summarizes the correlation between gut microbiota and depression and provides new pathways for effective treatments of depression.展开更多
Serotonin syndrome(SS)is a drug-induced clinical syndrome resulting from increased serotonergic activity in the central nervous system.Although more than seven decades have passed since the first description of SS,it ...Serotonin syndrome(SS)is a drug-induced clinical syndrome resulting from increased serotonergic activity in the central nervous system.Although more than seven decades have passed since the first description of SS,it is still an enigma in terms of terminology,clinical features,etiology,pathophysiology,diagnostic criteria,and therapeutic measures.The majority of SS cases have previously been reported by toxicology or psychiatry centers,particularly in people with mental illness.However,serotonergic medications are used for a variety of conditions other than mental illness.Serotonergic properties have been discovered in several new drugs,including over-the-counter medications.These days,cases are reported in non-toxicology centers,such as perioperative settings,neurology clinics,cardiology settings,gynecology settings,and pediatric clinics.Overdoses or poisonings of serotonergic agents constituted the majority of the cases observed in toxicology or psychiatry centers.Overdose or poisoning of serotonergic drugs is uncommon in other clinical settings.Patients may develop SS at therapeutic dosages.Moreover,these patients may continue to use serotonergic medications even if they develop mild to moderate SS due to several reasons.Thus,the clinical presentation(onset,severity,and clinical features)in such instances may not exactly match what toxicologists or psychiatrists observe in their respective settings.They produce considerable diversity in many aspects of SS.However,other experts discount these new developments in SS.Since SS is a potentially lethal illness,consensus is required on several concerns related to SS.展开更多
The antidepressive effect of Xiaoyaosan is doubtless by researches while the potential antidepressive ac- tive ingredients and their mechanisms remain unclear. In order to explain the antidepressive effect of Xiaoyaos...The antidepressive effect of Xiaoyaosan is doubtless by researches while the potential antidepressive ac- tive ingredients and their mechanisms remain unclear. In order to explain the antidepressive effect of Xiaoyaosan, all of the recent reports were sought out on the current situation of the antidepressive monomer compositions of Xi- aoyaosan and their mechanism. By exploring the relationship between the effects and the active ingredients, the mechanism and the active ingredients, the antidepressive active ingredients such as quercetin, isorhamnetin, isoliquiritigenin, saikosaponinA, saikosaponinD, glycyrrhiz- kaempferol, liquiritin, isoliquiritin, liquiritigenin, inate, paeoniflorin, albiflorin, ferulic acid, curcumin and their mechanism of antidepressive such as regulating the monoamine neurotransmitter systems, regulating the neuroendocrine system, affecting the neural plasticity and neu- affecting the cytokines level, anti-oxidative stress were rotrophic, affecting the cellular and molecular mechanisms , summarized. By the overview in the level of monomer rather than formulae, we uncovered the antidepressive mech- anism of Xiaoyaosan and further confirmed that Xiaoyaosan, as a classic antidepressive Chinese prescription, had many characteristics, such as multi-level , multi-channel, multi-target and so on .展开更多
Aim To study the influence of SiniSan on the Tryptophan- kynurenine（TRP-KYN）pathway, the activity and content of the key metabolism enzyme indoleamine2, 3-dioxygenase （IDO）. Methods The mice model was established ...Aim To study the influence of SiniSan on the Tryptophan- kynurenine（TRP-KYN）pathway, the activity and content of the key metabolism enzyme indoleamine2, 3-dioxygenase （IDO）. Methods The mice model was established by intraperitoneal injection LPS （ 1 mg · kg^-1 ）. Using ELISA to detect the contents of IFN-γin serum. The content of Tryptophan and kynurenine in brain tissue were detected by using HPLC-MS/MS technique. The mRNA expression level of IDO in brain tissue was detected by using real-time PCR. Results 4 hours after the LPS injection, the immobility time of model group mice prolonged. The content of IFN-~/in serum increased significantly （P 〈 0.05）. Meanwhile, the activity of IDO in brain tissue and the mRNA expression level of IDO increased. SiniSan could short the immobility time of mice, reduced the content of IFN-γin serum （P 〈 0.05）. It could also inhibit the activity of IDO and the expression of mRNA（P 〈 0.01 ）. Conclusion SiniSan blocks the pathway of IDO activation, inhibit the activity of IDO and reduce the content of it. SiniSan produces antidepressant effect by adjusting the TRP-KYN metabolism.展开更多
文摘Aim The study focused on identification and antidepression active verification of constituents from An- gelica Sinensis Radix contrubuting to Xiaoyaosan based on UPLC-PDA guided isolation technique. Methods The UPLC-PDA chromatogram of Xiaoyaosan was compared with that of Angelica Sinensis Radix. The relative retention time of each peak and the Uhraviolet spectra providing by PDA were used in the analyses. Constituents were isola- ted from Angelica Sinensis Radix under the guidance of UPLC-PDA investigation. Structures of the isolates were elu- cidated by NMR techniques. Anti-depression effect was evaluated on glutamate-induced neurons. Results Five marker peaks of Xiaoyaosan fingerprint were belong to Angelica Sinensis Radix, and they were determined as conife- ryl ferulate（ I）, E-butylidenephthalide （ II）, ligustilide （III）, Z-butylidenephthalide （ IV ）, 14-Acetoxy-12-sene- cioyloxytetradeca-2E,8E,10E-trien-4,6-diyn-l-ol（V）. Compound V was isolated from the plants of Umbelliferae for the first time. Treatment with compound I, III, IV can protect PC12 and SH-SY5Y cell from glutamate-induced cytotoxicity. Antidepression bioactivity of compound I was first investigated. Conclusion UPLC-PDA guided iso-lation technique was confirmed to be a rapid and accurate method to identify the main active constituents from An- gelica Sinensis Radix contrubuting to Xiaoyaosan.
基金supported by the National Natural Science Foundation of China,Nos.82204360(to HM)and 82270411(to GW)National Science and Technology Innovation 2030 Major Program,No.2021ZD0200900(to YL)。
文摘Traumatic brain injury involves complex pathophysiological mechanisms,among which oxidative stress significantly contributes to the occurrence of secondary injury.In this study,we evaluated hypidone hydrochloride(YL-0919),a self-developed antidepressant with selective sigma-1 receptor agonist properties,and its associated mechanisms and targets in traumatic brain injury.Behavioral experiments to assess functional deficits were followed by assessment of neuronal damage through histological analyses and examination of blood-brain barrier permeability and brain edema.Next,we investigated the antioxidative effects of YL-0919 by assessing the levels of traditional markers of oxidative stress in vivo in mice and in vitro in HT22 cells.Finally,the targeted action of YL-0919 was verified by employing a sigma-1 receptor antagonist(BD-1047).Our findings demonstrated that YL-0919 markedly improved deficits in motor function and spatial cognition on day 3 post traumatic brain injury,while also decreasing neuronal mortality and reversing blood-brain barrier disruption and brain edema.Furthermore,YL-0919 effectively combated oxidative stress both in vivo and in vitro.The protective effects of YL-0919 were partially inhibited by BD-1047.These results indicated that YL-0919 relieved impairments in motor and spatial cognition by restraining oxidative stress,a neuroprotective effect that was partially reversed by the sigma-1 receptor antagonist BD-1047.YL-0919 may have potential as a new treatment for traumatic brain injury.
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 National Natural Science Foundation of China(NSFC,81971734,32071323,32271410),the Program for Innovative Research Team in Science and Technology in Fujian Province.
文摘Aripiprazole(ARI),a second-generation atypical antipsychotic drug approved for schizophrenia treatment,shows good efficacy against depression.However,the poorly aqueous solubility of ARI leads to low bioavailability and increased dose-related side effects,seriously limiting its application in pharmaceutics.Herein,we demonstrated the fabrication of ARI and poly(methyl vinyl etherco-maleic anhydride)(PVMMA)composite nanoparticles(PA NPs)using the supercritical antisolvent(SAS)process for enhancing its water-solubility and curative anti-depressant effects.Initially,the optimal experimental conditions(ARI/PVMMA mass ratio of 1:6,pressure of 10MPa,and solution flow rate of 0.75ml min^(-1))were determined by a 23 factorial experimental design,resulting in the PA NPs with an excellent particle morphology.In vitro cell experiments showed that PA NPs significantly inhibited the inflammatory response caused by the microglia activation induced by lipopolysaccharide(LPS).Similarly,mice behavioral tests demonstrated that PA NPs significantly improved LPS-induced depression-like behavior.Importantly,compared with free ARI,the LPS-induced activation of microglia in the mouse brain and the expression of inflammatory factors in serum were significantly reduced after treatment with PA NPs.Together,the innovative PA NPs designed by SAS processmight provide a candidate for developing new ARI-based nano-formulations.
文摘BACKGROUND Traumatic brain injury(TBI)poses a considerable risk to human health.After TBI,individuals are susceptible to a range of psychiatric disorders,with depression being a primary complication.Selective serotonin reuptake inhibitors(SSRIs)are frequently used in the treatment of depression;however,their efficacy in addressing major depressive disorder(MDD)in adults following TBI remains uncertain.AIM To investigate the efficacy of SSRIs in the treatment of MDD after TBI.METHODS A comprehensive search across multiple databases was conducted following the guidelines outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement,encompassing studies published until May 2024.This review focused on studies that examined the efficacy of SSRIs in the treatment of MDD following TBI.Studies were assessed based sample size,treatment duration,treatment methodologies,severity of brain injury,assessment techniques,and drug response.A random-effects model was used to derive the summary effect size.RESULTS Eight studies compared the reduction in depression scores in patients with MDD after TBI and SSRI treatment.The eight studies did not exhibit heterogeneity(I^(2)=38%).The depression score for MDD after TBI in the SSRI group decreased more than that in the control group[odds ratio(OR)1.68,95%CI:1.09-2.58,P=0.02].The adverse reactions after treatment included diarrhea,dizziness,dry mouth,nausea,or vomiting.There was no difference in the incidence of adverse reactions after treatment between the two groups(OR 1.16,95%CI:0.78-1.73,P=0.46).These studies did not show significant heterogeneity(I^(2)=44%).CONCLUSION SSRIs may be effective in treating patients with MDD after TBI.Adequately powered,randomized,controlled trials are required to confirm these findings.
基金Supported by the National Institutes of Health/National Institute on Aging,No.1R21AG091282.
文摘Agitation is a neuropsychiatric syndrome characterized by excessive motor and/or verbal behaviors,with or without aggressive behaviors.The prevalence of agitation in Alzheimer’s disease varies from 5%to over 50%.Multiple factors have been implicated in its pathophysiology,including disease stage,comorbidity with other symptoms(e.g.,psychosis,anxiety/depression),and psychosocial factors.Ruling out delirium and identifying environmental triggers are fundamental steps in the management of agitation in Alzheimer’s disease.For establishing an effective therapeutic plan,it is important to define duration,severity,and potential for harm.While non-pharmacological approaches are considered the first line of intervention,pharmacological agents are frequently used in the treatment of agitation.Antipsychotics are commonly used in acute agitation.For chronic agitation,serotonin-selective reuptake inhibitors,especially citalopram and escitalopram,are often preferred due to safety concerns associated with the longterm use of antipsychotics.Promising novel strategies,such as new compounds and neuromodulation,are likely to be incorporated into agitation therapeutics in the next few years.
基金Supported by Undergraduate Innovation and Enterpreneurship Training Program of Guangxi(S202310600067)Guangxi First-class Discipline Construction Project(GJKY[2022]1).
文摘[Objectives]This study was conducted to perform visual analysis of the research hotspots and development trends of Cyperi Rhizoma in the field of antidepressant based on CiteSpace,so as to explore the application and development direction of Cyperi Rhizoma in the field of antidepressant.[Methods]Highly-relevant literatures were selected from the core database of China National Knowledge Infrastructure(CNKI),and CiteSpace and WPS office software were employed to visually analyze relevant contents such as publishing institutions,scholars,keywords,publishing time,and citation frequency.[Results]A total of 297 domestic relevant literatures were selected.Most of the publications,institutions and authors were concentrated in universities,affiliated institutions and scientific research institutes of traditional Chinese medicine in China,and no relatively novel applied research direction has emerged.At present,the hot spots and frontiers of application were mostly concentrated in its role in treating depression,anxiety,gynecological diseases and other disorders.[Conclusions]The research on Cyperi Rhizoma for its antidepressant effects in China originated in the late 20 th century.From 2004 to 2024,studies have primarily focused on its pharmacological principles,mechanisms of action,and classification,while the exploration of its application in specific depressive disorders was limited.Overall,research progress has been relatively slow.Currently,further efforts are needed to optimize the active antidepressant components of Cyperi Rhizoma and clarify its mechanisms of action,which will facilitate its broader application in treating various stages of depressive disorders.
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A recent meta-analysis has suggested a 5-HTR1A promoter variant may predict antidepressant response.The present review comments on the claims made in view of sensitivity issues and issues pertaining to genetic exposure.We also alert to errors in the original data that had been carried over.Specifically,primers meant to amplify the HTR1A gene aligned to the BDNF gene sequence.Alleles had been confounded owing to DNA strand ambiguities and demographic information proved inaccurate.In the light of these findings,adherence to PRISMA guidelines and use of the Newcastle-Ottawa Scale did not safeguard against bias.More after action reviews are encouraged to identify factors likely to interfere with estimates of genetic risk in large data sets.These may result from pooling of ethnic groups,the use of binary data or other formats that are not human-readable,the introduction of surrogate identifiers and a failure to reverseengineer previously published experimental protocols.Unless the above challenges are met,sequence variants are unlikely to inform personalized medicine strategies in psychiatry.
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financially supported by the National Nature Science Foundation of China,Nos.82271508(to YC)82001384(to YC)82271316(to HG)。
文摘Although antipsychotics that act via monoaminergic neurotransmitter modulation have considera ble therapeutic effect,they cannot completely relieve clinical symptoms in patients suffering from psychiatric disorde rs.This may be attributed to the limited range of neurotransmitters that are regulated by psychotropic drugs.Recent findings indicate the need for investigation of psychotropic medications that target less-studied neurotransmitte rs.Among these candidate neurotransmitters,lactate is developing from being a waste metabolite to a glial-neuronal signaling molecule in recent years.Previous studies have suggested that cerebral lactate levels change considerably in numerous psychiatric illnesses;animal experiments have also shown that the supply of exogenous la ctate exerts an antidepressant effect.In this review,we have described how medications targeting newer neurotransmitte rs offer promise in psychiatric diseases;we have also summarized the advances in the use of lactate(and its corresponding signaling pathways)as a signaling molecule.In addition,we have described the alterations in brain lactate levels in depression,anxiety,bipolar disorder,and schizophrenia and have indicated the challenges that need to be overcome before brain lactate can be used as a therapeutic target in psychopharmacology.
基金supported by the National Key Research and Development Program of China (2021YFD2100402)the National Natural Science Foundation of China (81903275)the Fund of the Cultivation Project of Double First-Class Disciplines of Food Science and Engineering,Beijing Technology&Business University (BTBUYXTD202203)。
文摘Globally,the prevalence of anxiety and depression has reached epidemic proportions.Food-derived protein hydrolysates and peptides delivered through dietary supplementation can avoid the negative risks associated with traditional pharmaceuticals while delivering superior anxiolytic and antidepressant effects.This review summarizes current research on food-derived anxiolytic and antidepressant protein hydrolysates and peptides,and subsequently analyses their physicochemical characteristics and elaborates on their mechanisms.The aim of this work is to contribute to the in-depth study and provide a theoretical foundation for the development of related products to better serve patients with anxiety and depression.
文摘γ-Aminobutyric acid(GABA) neurotransmission alterations have been implicated to play a role in depression pathogenesis. While GABA_(A) receptor positive allosteric modulators are emerging as promising in clinical practice, their precise antidepressant mechanism remains to be further elucidated. The aim of the present study was to investigate the effects of LY-02, a novel compound derived from the metabolite of timosaponin, on depression in animals and its mechanism. The results of behavioral tests showed that LY-02 exhibited better antidepressant effects in both male C57BL/6 mice and Sprague Dawley(SD) rats. The results of cellular voltage clamp experiments showed that LY-02 enhanced GABA-mediated currents in HEK293T cells expressing recombinant α6β3δ subunitcontaining GABA_(A) receptors. Electrophysiological recording from brain slices showed that LY-02 decreased the amplitude of spontaneous inhibitory postsynaptic current(sIPSC) and increased action potentials of pyramidal neurons in the medial prefrontal cortex(mPFC) of C57BL/6 mice. Western blot results showed that LY-02 dose-dependently up-regulated the protein expression levels of brain-derived neurotrophic factor(BDNF), tropomyosin related kinase B(TrkB) and postsynaptic density protein 95(PSD-95) in m PFC of mice. The above results suggest that LY-02, as a positive modulator of GABA_(A) receptors, reduces inhibitory neurotransmission in pyramidal neurons. It further activates the BDNF/TrkB signaling pathway, thus exerting antidepressant effects. It suggests that LY-02 is a potential novel therapeutic agent for depression treatment.
文摘BACKGROUND Major depressive disorder(MDD)is a substantial global health concern,and its treatment is complicated by the variability in individual response to antide-pressants.AIM To consolidate research and clarify the impact of genetic variation on MDD treatment outcomes.METHODS Adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines,a systematic search across PubMed,EMBASE,Web of Science,and the Cochrane Library was conducted without date restrictions,utilizing key terms related to MDD,serotonin 1A receptor polymorphism(5-HTR1A),C-1019G polymorphism,and antidepressant response.Studies meeting inclusion criteria were thoroughly screened,and quality assessed using the Newcastle-Ottawa Scale.Statistical analyses,includingχ2 and I²values,were used to evaluate heterogeneity and fixed-effect or random-effect models were applied accordingly.RESULTS The initial search yielded 1216 articles,with 11 studies meeting criteria for inclusion.Analysis of various genetic models showed no significant association between the 5-HTR1A C-1019G polymorphism and antidepressant efficacy.The heterogeneity was low to moderate,and no publication bias was detected through funnel plot symmetry and Egger's and Begg's tests.CONCLUSION This meta-analysis does not support a significant association between the 5-HTR1A C-1019G polymorphism and the efficacy of antidepressant treatment in MDD.The findings call for further research with larger cohorts to substantiate these results and enhance the understanding of antidepressant pharmacogenetics.
基金supported by the Showalter Research Trust Fund (to XG)Indiana Spinal Cord&Brain Injury Research Fund (ISCBIRF) from the Indiana State Departm ent of Health (to XG)。
文摘It has been reported both in clinic and rodent models that beyond spinal cord injury directly induced symptoms, such as paralysis, neuropathic pain, bladder/bowel dysfunction, and loss of sexual function, there are a variety of secondary complications, including memory loss, cognitive decline, depression, and Alzheimer's disease. The largescale longitudinal population-based studies indicate that post-trauma depression is highly prevalent in spinal cord injury patients. Yet, few basic studies have been conducted to address the potential molecular mechanisms. One of possible factors underlying the depression is the reduction of adult hippocampal neurogenesis which may come from less physical activity, social isolation, chronic pain, and elevated neuroinflammation after spinal cord injury. However, there is no clear consensus yet. In this review, we will first summarize the alteration of hippocampal neurogenesis post-spinal cord injury. Then, we will discuss possible mechanisms underlie this important spinal cord injury consequence. Finally, we will outline the potential therapeutic options aimed at enhancing hippocampal neurogenesis to ameliorate depression.
文摘Depression can be counted as the most severe mental disease in the world nowadays, which lacks effective curing treatments. With an increasing number of patients, developing effective treatments with fewer side effects is essential. Medicinal food homology has been proven to influence the pathogenesis of depression positively. Gut microbiota plays a vital role in exerting the antidepressant effect of substances from the medicinal food homology, as they facilitate different chemical processes and increase the bioavailability of the substances. This review summarizes the correlation between gut microbiota and depression and provides new pathways for effective treatments of depression.
文摘Serotonin syndrome(SS)is a drug-induced clinical syndrome resulting from increased serotonergic activity in the central nervous system.Although more than seven decades have passed since the first description of SS,it is still an enigma in terms of terminology,clinical features,etiology,pathophysiology,diagnostic criteria,and therapeutic measures.The majority of SS cases have previously been reported by toxicology or psychiatry centers,particularly in people with mental illness.However,serotonergic medications are used for a variety of conditions other than mental illness.Serotonergic properties have been discovered in several new drugs,including over-the-counter medications.These days,cases are reported in non-toxicology centers,such as perioperative settings,neurology clinics,cardiology settings,gynecology settings,and pediatric clinics.Overdoses or poisonings of serotonergic agents constituted the majority of the cases observed in toxicology or psychiatry centers.Overdose or poisoning of serotonergic drugs is uncommon in other clinical settings.Patients may develop SS at therapeutic dosages.Moreover,these patients may continue to use serotonergic medications even if they develop mild to moderate SS due to several reasons.Thus,the clinical presentation(onset,severity,and clinical features)in such instances may not exactly match what toxicologists or psychiatrists observe in their respective settings.They produce considerable diversity in many aspects of SS.However,other experts discount these new developments in SS.Since SS is a potentially lethal illness,consensus is required on several concerns related to SS.
文摘The antidepressive effect of Xiaoyaosan is doubtless by researches while the potential antidepressive ac- tive ingredients and their mechanisms remain unclear. In order to explain the antidepressive effect of Xiaoyaosan, all of the recent reports were sought out on the current situation of the antidepressive monomer compositions of Xi- aoyaosan and their mechanism. By exploring the relationship between the effects and the active ingredients, the mechanism and the active ingredients, the antidepressive active ingredients such as quercetin, isorhamnetin, isoliquiritigenin, saikosaponinA, saikosaponinD, glycyrrhiz- kaempferol, liquiritin, isoliquiritin, liquiritigenin, inate, paeoniflorin, albiflorin, ferulic acid, curcumin and their mechanism of antidepressive such as regulating the monoamine neurotransmitter systems, regulating the neuroendocrine system, affecting the neural plasticity and neu- affecting the cytokines level, anti-oxidative stress were rotrophic, affecting the cellular and molecular mechanisms , summarized. By the overview in the level of monomer rather than formulae, we uncovered the antidepressive mech- anism of Xiaoyaosan and further confirmed that Xiaoyaosan, as a classic antidepressive Chinese prescription, had many characteristics, such as multi-level , multi-channel, multi-target and so on .
文摘Aim To study the influence of SiniSan on the Tryptophan- kynurenine（TRP-KYN）pathway, the activity and content of the key metabolism enzyme indoleamine2, 3-dioxygenase （IDO）. Methods The mice model was established by intraperitoneal injection LPS （ 1 mg · kg^-1 ）. Using ELISA to detect the contents of IFN-γin serum. The content of Tryptophan and kynurenine in brain tissue were detected by using HPLC-MS/MS technique. The mRNA expression level of IDO in brain tissue was detected by using real-time PCR. Results 4 hours after the LPS injection, the immobility time of model group mice prolonged. The content of IFN-~/in serum increased significantly （P 〈 0.05）. Meanwhile, the activity of IDO in brain tissue and the mRNA expression level of IDO increased. SiniSan could short the immobility time of mice, reduced the content of IFN-γin serum （P 〈 0.05）. It could also inhibit the activity of IDO and the expression of mRNA（P 〈 0.01 ）. Conclusion SiniSan blocks the pathway of IDO activation, inhibit the activity of IDO and reduce the content of it. SiniSan produces antidepressant effect by adjusting the TRP-KYN metabolism.
