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
Recent studies have shown that a 9-hour fast in mice reduces the amount of time spent immobile in the forced swimming test.Howeve r,whether 9-hour fasting has therapeutic effects in female mice with depressive symptom...Recent studies have shown that a 9-hour fast in mice reduces the amount of time spent immobile in the forced swimming test.Howeve r,whether 9-hour fasting has therapeutic effects in female mice with depressive symptoms has not been established.Therefore,in this study,we simulated perimenopausal depression via an ovariectomy in mice,and subjected them to a single 9-hour fasting 7 days later.We found that the ovariectomy increased the time spent immobile in the forced swimming test,inhibited expression of the mammalian target of rapamycin complex 1 signaling pathway in the hippocampus and prefro ntal cortex,and decreased the density of dendritic spines in the hippocampus.The 9-hour acute fasting alleviated the above-mentioned phenomena.Furthermore,all of the antidepressant-like effects of 9-hour fasting were reve rsed by an inhibitor of the mammalian to rget of rapamycin complex 1.Electrophysiology data showed a remarkable increase in long-term potentiation in the hippocampal CA1 of the ovariectomized mice subjected to fasting compared with the findings in the ovariectomized mice not subjected to fasting.These findings show that the antidepressant-like effects of 9-hour fasting may be related to the activation of the mammalian target of the rapamycin complex 1 signaling pathway and synaptic plasticity in the mammalian hippocampus.Thus,fasting may be a potential treatment for depression.展开更多
Depression,a prevalent mood disorder,has emerged as a significant health concern in society.While the exact cause of depression remains incompletely understood,there is substantial evidence linking the gastrointestina...Depression,a prevalent mood disorder,has emerged as a significant health concern in society.While the exact cause of depression remains incompletely understood,there is substantial evidence linking the gastrointestinal microbiome and its metabolites to this condition.Through combined multi-omics analysis,it has been observed that the composition of the gastrointestinal microbiome,including Firmicutes,Bacteroidetes,and Actinobacteria,undergoes significant alterations in depressed individuals.Moreover,the production of short-chain fatty acids,tryptophan,and bile acids by these gut microbes is also found to be modified in depression.Furthermore,studies have demonstrated that antidepressant medications exert their therapeutic effects by interacting with the gastrointestinal microbiome and their metabolites.This review provides an overview of the association between the gastrointestinal microbiome,related metabolites,and depression.It highlights the potential of these factors to serve as mechanisms of action for antidepressant medications.Additionally,the review summarizes the commonly used technical tools in depression research.展开更多
QT interval prolongation can be categorized into primary and secondary types according to its etiology.In this paper,we report a case of severe asymptomatic QT interval prolongation secondary to antidepressants.Regula...QT interval prolongation can be categorized into primary and secondary types according to its etiology.In this paper,we report a case of severe asymptomatic QT interval prolongation secondary to antidepressants.Regular follow-up and electrocardiogram monitoring is crucial when applying antidepressants,especially for patients without cardiac symptoms.This article presents case studies and examines existing literature on long QT syndrome to enhance the diagnosis and management of QT interval prolongation.This is especially relevant for non-psychiatric healthcare professionals who need to be attentive to the side effects of antidepressants to prevent potential adverse consequences resulting from oversight.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
The pathophysiology of depression has been traditionally attributed to a chemical imbalance and critical interactions between genetic and environmental risk factors, and antidepressant drugs suggested to act predomina...The pathophysiology of depression has been traditionally attributed to a chemical imbalance and critical interactions between genetic and environmental risk factors, and antidepressant drugs suggested to act predominantly amplifying monoaminergic neurotransmission. This conceptualization may be currently considered reductive. The current literature about the pathophysiological mechanisms underlying depression, stress-related disorders and antidepressant treatment was examined. In order to provide a critical overview about neuroplasticity, depression and antidepressant drugs, a detailed Pubmed/Medline, Scopus, Psyc Lit, and Psyc Info search to identify all papers and book chapters during the period between 1980 and 2011 was performed. Pathological stress and depression determine relevant brain changes such as loss of dendritic spines and synapses, dendritic atrophy as well as reduction of glial cells(both in number and size) in specific areas such as the hippocampus and prefrontal cortex. An increased dendritic arborisation and synaptogenesis may instead be observed in the amygdala as a consequence of depression and stress-related disorders. While hippocampal and prefrontal functioning was impaired, amygdala functioning was abnormally amplified. Most of molecular abnormalities and biological changes of aberrant neuroplasticity may be explained by the action of glutamate. Antidepressant treatment is associated with neurogenesis, gliogenesis, dendritic arborisation, new synapse formation and cell survival both in the hippocampus and prefrontal cortex. Antidepressants(ADs) induce neuroplasticity mechanisms reversing the pathological effects of depression and stress-related disorders. The neuroplasticity hypothesis may explain the therapeutic and prophylactic action of ADs representing a new innovative approach to the pathophysiology of depression and stress-related disorders.展开更多
Inflammatory bowel disease (IBD) is a group of inflammatory disorders mainly affecting the colon and small intestine. The main types of IBD are Crohn’s disease (CD) and ulcerative colitis (UC). UC is restricted to th...Inflammatory bowel disease (IBD) is a group of inflammatory disorders mainly affecting the colon and small intestine. The main types of IBD are Crohn’s disease (CD) and ulcerative colitis (UC). UC is restricted to the large intestine whereas CD can affect any part of the gastrointestinal tract. Treating this disorder depends on the form and level of severity. Common treatment involves an anti-inflammatory drug, such as mesalazine, and an immunosuppressant, such as prednisone. Several signaling pathways, including nuclear factor (NF)-κB and nitric oxide (NO), and genetic and environmental factors are believed to play an important role in IBD. Amitriptyline is a commonly used antidepressant with known anti-inflammatory activities. Amitriptyline also acts on the NF-κB/NO pathway or cytokine production. Therefore, we hypothesize that antidepressants like amitriptyline can be pioneered and considered effective as an innovative and effective therapeutic in the treatment and attenuation of development of IBD in adjusted doses.展开更多
This work evaluates intercalation of Nortriptyline(NT)and Venlafaxine(VFX)in an interlayer gallery of Na^(+)-MMT(Montmorillonite),which was further compounded with Poly(LLactide)(PLLA)to form microcomposite spheres(MP...This work evaluates intercalation of Nortriptyline(NT)and Venlafaxine(VFX)in an interlayer gallery of Na^(+)-MMT(Montmorillonite),which was further compounded with Poly(LLactide)(PLLA)to form microcomposite spheres(MPs)for oral controlled drug delivery.The XRD patterns,thermal and spectroscopic analyses indicated intercalation of drugs into the MMT interlayer that was stabilized by electrostatic interaction.No significant changes in structural and functional properties of drugs were found in the MMT layers.In vitro drug release studies showed controlled release pattern.展开更多
Objective:Acorus calamus(AC)L.(Araceae)is an annual semi-aquatic and aromatic plant found in Europe,North America and Asia.Its rhizomes are often used by Native Americans,Americans,and Chinese as well as by other cult...Objective:Acorus calamus(AC)L.(Araceae)is an annual semi-aquatic and aromatic plant found in Europe,North America and Asia.Its rhizomes are often used by Native Americans,Americans,and Chinese as well as by other cultures.Ethnobotanical studies and documents have shown their use in various disease treatments,such as insomnia,mental disorders,diabetes mellitus,epilepsy,inflammation,asthma,neuropathic pain,and diarrhea.In this study,the antidepressant activity of methanolic and hydroalcoholic extracts of the AC rhizome part in mice was investigated.Methods:Three doses of methanolic extract of AC rhizome(MEACR)(25,50 and 100 mg/kg b.wt),three doses of hydroalcoholic extract of AC rhizome(HAACR)(100,200 and 400 mg/kg b.wt),and standards(imipramine,15 mg/kg b.wt and fluoxetine,20 mg/kg b.wt)was daily oral administration to the mice for consecutive 14 days.The extract effect on the immobility time was monitored by a tail suspension test(TST)and a forced swimming test(FST).Monoamine oxidase(MAO)levels were also analyzed using standard methods.Results:The optimum antidepressant activity was viewed at 100 mg/kg b.wt of MEACR extract and400 mg/kg b.wt of HAACR extract with 23.82%and 20.59%immobility period reduction,respectively.Besides,the extracts weakened the FST-induced elevation of MAO activity significantly and returned to near-normal levels of neurotransmitters in the brain.100 mg/kg b.wt or above of MEACR extract significantly prevented the MAO-A and MAO-B activities in mice brain at a dose-dependent fashion.But,just 400 mg/kg b.wt of HAACR extract prevented the activity of MAO-A and MAO-B.Fluoxetine and imipramine showed a tendency to prevent the activity of MAO-A and MAO-B.Conclusion:This study suggests that AC rhizome extract mediated antidepressant activity by modulating the central neurochemical and hypothalamic-pituitary-adrenal(HPA)axis in response to FST and TSTinduced stress.Therefore,AC rhizome extract can be used as a valuable plant supplement to treat depressive disorders.展开更多
Objective: Although antidepressants are the recommended first-line pharmacological treatments for depressive and anxiety disorders, their prescribing patterns have not been studied in Singapore. We investigate antidep...Objective: Although antidepressants are the recommended first-line pharmacological treatments for depressive and anxiety disorders, their prescribing patterns have not been studied in Singapore. We investigate antidepressant prescription patterns for outpatients with depressive and anxiety disorders in a general hospital in Singapore. We hypothesize that intolerance to side effects and lack of efficacy may contribute to medication switching, and that initiation of antidepressant therapy is not easily tolerated. Methods: A retrospective review of the casenotes of outpatients was carried out between January 2013 and December 2013. A total of 206 patients were randomly selected. The study was approved by the hospital’s institutional review board. Data analysis was carried out using SPSS version 18. Results: There were more females than males (ratio 1.7:1) with a mean age of 50.6 ± 15.2 years. Depressive disorder, comprising 50% of the sample, was the most frequent diagnosis followed by anxiety disorder (27.2%), mixed anxiety-depression (16%) and adjustment disorder (5.8%). Almost all patients (97.1%) were prescribed antidepressants, the most common being selective serotonin reuptake inhibitors (SSRI) (75.5%), followed by the noradrenaline and specific serotonin antidepressant (NaSSA) (13.5%) and tricyclic antidepressants (TCA) (8.5%). Patients prescribed SSRIs tended to be younger and better educated (p = 0.0005). More than half of the patients (52.1%) required antidepressant switching mainly due to lack of efficacy and intolerance of side effects. Combination therapy was prescribed for 17% of patients with SSRI-NaSSA, the most preferred combination. Nearly a quarter (23.8%) patients required augmentation therapy with atypical antipsychotics. Combination (p = 0.024) and augmentation (p = 0.033) were utilized more often for depression than for anxiety disorders. Conclusion: Antidepressant medications are commonly prescribed for depression and anxiety disorders. The main reasons for switching antidepressants were intolerance and lack of efficacy. That about half of the patients reported side effects necessitating medication change confirmed our hypothesis that antidepressant therapy was not easy to initiate. This has important implications for treatment adherence and outcome.展开更多
Major depressive disorder(MDD)is a disabling and highly prevalent mood disorder as well as a common cause of suicide.Chronic stress,inflammation,and intestinal dysbiosis have all been shown to play crucial roles in th...Major depressive disorder(MDD)is a disabling and highly prevalent mood disorder as well as a common cause of suicide.Chronic stress,inflammation,and intestinal dysbiosis have all been shown to play crucial roles in the pathophysiology of MDD.Although conventional antidepressants are widely used in the clinic,they can take weeks to months to produce therapeutic effects.The discovery that ketamine promotes fast and sustaining antidepressant responses is one of the most important breakthroughs in the pharmacotherapy of MDD.However,the adverse psychomimetic/dissociative and neurotoxic effects of ketamine discourage its chronic use.Therefore,agmatine,an endogenous glutamatergic modulator,has been postulated to elicit fast behavioral and synaptogenic effects by stimulating the mechanistic target of rapamycin complex 1 signaling pathway,similar to ketamine.However,recent evidence has demonstrated that the modulation of the NLR family pyrin domain containing 3 inflammasome and gut microbiota,which have been shown to play a crucial role in the pathophysiology of MDD,may also participate in the antidepressant-like effects of both ketamine and agmatine.This review seeks to provide evidence about the mechanisms that may underlie the fast antidepressant-like responses of agmatine in preclinical studies.Considering the anti-inflammatory properties of agmatine,it may also be further investigated as a useful compound for the management of MDD associated with a pro-inflammatory state.Moreover,the fast antidepressant-like response of agmatine noted in animal models should be investigated in clinical studies.展开更多
OBJECTIVE To find that the extracellular cap of a K2P channel can act as a new allosteric site and may serve as a direct drug target.METHODS Molecular biology and cell transfection,electrophysiology,molecular docking,...OBJECTIVE To find that the extracellular cap of a K2P channel can act as a new allosteric site and may serve as a direct drug target.METHODS Molecular biology and cell transfection,electrophysiology,molecular docking,molecular dynamics simulations,virtual screening for TREK1,and depressive-related behavior tests.RESULTS Extracellular domain of TREK1 channel existed a dynamic cavity in the extracellular domain by the method of computations,mutagenesis and electrophysiology.Molecular dynamics simulations suggested that ligand-induced allosteric conformational transitions lead to blockage of the ion conductive pathway.Using virtual screening approach,we identified other inhibitors targeting the extracellular allosteric ligand-binding site of these channels.Overall,our results suggested that the allosteric site at the extracellular cap of the K2P channels might be a promising drug target for these membrane proteins.The TREK1 inhibitor TKDC had significantly faster onset than that of fluoxetine in chronic administration trials,and the study confirms that TREK1 was an important target for the development of rapid antidepressants.CONCLUSION The study is a significant step forward for understanding the function of TREK and for identifying specific inhibitors,which should be of interest to others in the field.展开更多
Medicinal plants and their ingredients have beneficial effects on human health.Nigella sativa is a herbal plant with multiple biological and pharmacological activities.Previous studies demonstrated the anti-inflammato...Medicinal plants and their ingredients have beneficial effects on human health.Nigella sativa is a herbal plant with multiple biological and pharmacological activities.Previous studies demonstrated the anti-inflammatory and antioxidant properties of Nigella sativa and its main constituent thymoquinone significantly contributes to the antidepressant and anti-nociception effects of this plant.It has been reported that thymoquinone may achieve its antidepressant effect by preventing the elimination of brain neurotransmitters affecting depression such as serotonin.The role of brain-derived neurotrophic factors in the antidepressant effects of thymoquinone has also been documented.Additionally,thymoquinone can attenuate pain by upregulation of intracellular signaling pathways related to nitric oxide and K_(ATP)^(+)channels.The present review summarizes the antidepressant and anti-nociceptive activity of Nigella sativa and its main constituent thymoquinone by searching literature on electronic databases such as PubMed,Web of Science,Scopus,and Google Scholar from the beginning of 2010 until the end of August 2022.展开更多
OBJECTIVE Phosphodiesterase 4(PDE4),specific for cyclicAMP(cAMP)-hydrolyzing,has four isoforms(PDE4A-D) with at least 25 splice variants. PDE4 inhibitors produce definite antidepressant-like and cognitive-enhancing ef...OBJECTIVE Phosphodiesterase 4(PDE4),specific for cyclicAMP(cAMP)-hydrolyzing,has four isoforms(PDE4A-D) with at least 25 splice variants. PDE4 inhibitors produce definite antidepressant-like and cognitive-enhancing effects. However,none of PDE4 inhibitors has yet been approved for clinical utility so far due to the concomitant side effects. The present research is to explore the splice variants of PDE4 D responsible for antidepressant-like and cognitive-enhancing effects of PDE4 inhibitors but not side effects. METHODS Long-form PDE4 Ds were silenced by the bilateral microinfusion of lentiviral vector containing mi RNAs(4Dmi R) into the prefrontal cortex(PFC),PDE4D4 or D5 was overexpressed by the bilateral microinfusion of lentiviral vector containing full c DNA into hippocampus. Antidepressant-like behaviors were measured by tail-suspension test(TST),forced swimming test(FST)and chronic unpredictable stress model. Cognitive behaviors were measured by the novel object recognition test(NOR) and Morris water maze test(MWM) in both normal mice and the mice with chronic unpredictable stress-induced memory deficits. The emetic potential was evaluated by the assessment of the anaesthetic reversal effect,a surrogate of the emesis test in non-vomiting species. The expressions of PDE4 isoforms/splice variants and cAMP level were examined by Western-blot and ELISA analysis. The dendritic complexity and spine density were assessed by Golgi staining. RESULTS(1)High and specific expression of EGFP(green,indicator of 4Dmi R expression) in PFC was observed under fluorescence microscopy.(2) 4Dmi R significantly down-regulated PDE4D4/5 splice variants,but not PDE4 A,PDE4 B or PDE4D1/2/3.(3) 4Dmi R treatments significantly increased cAMP signaling and dendritic complexity in PFC.(4) Rolipram and/or 4Dmi R treatments significantly decreased immobility in TST and FST.(5) Rolipram and/or 4Dmi R treatments reversed the depressive-like behaviors in chronically stressed mice,including the reduced sucrose preference,prolonged latency to novelty-suppressed feeding and increased immobility in FST.(6) Rolipram and/or 4Dmi R treatments significantly increased the recognition index in NOR task and both the entries and durations in MWM task.(7) Rolipram and/or 4Dmi R treatments reversed the memory deficits in chronically stressed mice,including the reduced the recognition index in NOR task and the decreased durations in MWM task.(8) Rolipram and/or 4DmiR treatments reversed the decreased cA MP signaling,dendritic complexity and spine density.(9) Rolipram or plus 4Dmi R treatment significantly decreased the duration of anaesthesia in the alpha2 adrenergic receptor-mediated anesthesia,but not 4Dmi R treatment alone.(10)Hippocampal overexpression of PDE4D5,but not PDE4D4,produced depressive-like and cognitive defect behaviors,which were reversed by rolipram.The measurements including cAMP signaling,dendritic complexity and in vivo hippocampal LTP,showed the same changes. CONCLUSION Long-form PDE4 Ds,especially the PDE4D5,are the major isoforms responsible for antidepressant-like and cognitive-enhancing effects with little side effects. The critical roles of long-form PDE4 Ds are mediated by their regulation of cAMP signaling pathway and neuroplasticity.展开更多
Currently, accumulating studies indicated that upregulation of glycogen synthase kinase-3β （GSK3β） played an important role in depression pathogenesis. Our previous study demonstrated that ammoxetine, a novel se- ...Currently, accumulating studies indicated that upregulation of glycogen synthase kinase-3β （GSK3β） played an important role in depression pathogenesis. Our previous study demonstrated that ammoxetine, a novel se- rotonin and norepinephrine uptake inhibitor, displayed antidepressant activity more potent and faster than existing antidepressants, which may be clue to the increasing of hippocampal inhibitory serine-phosphorylation of glycogen synthase kinase-3 （GSK3）. The present study was to evaluate whether activation of PI3K/Akt signaling, one of the most important pathways regulating the phosphorylation of GSK3β, was required for ammoxetine induced antide- pressant effects and upregulation of pGSK3β. Behavioral results indicated that acute oral administration of ammoxe- tine at 10 mg/kg produced robust antidepressant effects in the forced swimming test and learned helpless test in mice, which were blocked totally by phosphatidylinositol （PI3）-kinase （PI3K） inhibitor LY294002. Then, West- ern blot results demonstrated that ammoxetine induced increasing of GSK3 β phosphorylation and activation of PI3 K/ Akt signaling can also be antagonized at the same testing time points by LY294002. These findings suggest that ac- tivation of PI3 K/Akt/GSK3[3 signaling is pivotal and necessary for the antidepressant effects of ammoxetine in the forced swimming test and learned helpless test in mice.展开更多
[Objectives]To study the content and antidepressant effects of the flavonoids in the Zanthoxylum Pericarpium Residue(ZPR)and to provide a basis for the full utilization of ZPR.[Methods]The method for the assay of tota...[Objectives]To study the content and antidepressant effects of the flavonoids in the Zanthoxylum Pericarpium Residue(ZPR)and to provide a basis for the full utilization of ZPR.[Methods]The method for the assay of total flavonoids in ZPR by UV spectrophotometry was developed with rutin as reference.The total flavonoids were extracted and separated from ZPR.The contents of total flavonoids were quantified in ZPR and its extract.The autonomous activity test,tail suspension test and forced swimming test were conducted in mice,and the levels of malondialdehyde(MDA),superoxide dismutase(SOD)and total antioxidation were detected to evaluate the antidepressant effects of total flavonoids.[Results]The recovery rate of UV spectrophotometry was 98.88%(n=6).The contents of flavonoids in ZPR and its extract were 11.07%and 78.42%,respectively.In the autonomous activity test,compared with the control group,the standing times of mice in the positive drug group was significantly increased(P<0.05),but there was not significant difference among the low-,medium-and high-dose groups of total flavonoids extract(P>0.05),as well as there was no significant difference of the activity times among all groups(P>0.05).In the tail suspension and forced swimming tests,compared with the control group,the immobility time of the high-dose group of total flavonoids extract was significantly reduced(P>0.05),and the serum SOD levels of the low-,medium-and high-dose groups were significantly increased(P<0.05).The MDA levels of the middle-and high-dose groups of total flavonoids were significantly decreased(P<0.05),and the total antioxidant capacity was increased significantly(P<0.05).[Conclusions]The developed UV spectrophotometry can accurately detect the level of total flavonoids in ZPR.ZPR is rich in flavonoids,and has significant antidepressant effects,which may be related to eliminating internal free radicals and inhibiting lipid peroxidation.展开更多
The role played by serendipity in the origin of modern psychopharmacology has proven to be controversial in scientific literature.In its original meaning(Walpole),serendipity refers to discoveries made through a combi...The role played by serendipity in the origin of modern psychopharmacology has proven to be controversial in scientific literature.In its original meaning(Walpole),serendipity refers to discoveries made through a combination of accidents and sagacity.We have implemented an operational definition of serendipity based on finding something unexpected or unintended,regardless of the systematic process that led to the accidental observation,and we have established four different patterns of serendipitous attributability.In this paper,we have analyzed the role of serendipity in the discovery and development of classical antidepressant drugs,tricyclic antidepressants and monoamine oxidase inhibitors as well as heterocyclic,“atypical”or“second generation”antidepressants.The discovery of the antidepressant properties of imipramine and iproniazid,the prototypes of tricyclic antidepressants and monoamine oxidase inhibitors,respectively,fits the mixed type II pattern;initial serendipitous discoveries(imipramine was an antipsychotic and iproniazid was an antituberculosis agent)led secondarily to non-serendipitous discoveries.But the other components of these two families of drugs were developed specifically as antidepressants,modifying the chemical structure of the series leaders,thereby allowing all of them to be included in the type IV pattern,characterized by the complete absence of serendipity.Among the heterocyclic drugs,mianserin(originally developed as an antihistamine)also falls into the type II pattern.展开更多
Epilepsy is a disorder in the nervous system which often causes a loss of consciousness. Traditional treatments are quiet a component of health care system in various populations in spite of the fact that well-establi...Epilepsy is a disorder in the nervous system which often causes a loss of consciousness. Traditional treatments are quiet a component of health care system in various populations in spite of the fact that well-established options are available. Most plants are used to treat epilepsy or those which have been verified for anticonvulsant activity were reported. Then, Costus afer is a plant of the Congolese flora used in traditional medicine for its many virtues. Therefore, the anticonvulsant activity of Costus afer was assessed with the strychnine convulsion induction test. Two tests were used for sedative activity such as the barbiturate sleep induction test and motor activity and finally the forced swimming test was also used to assess antidepressant activity. The results showed that the aqueous extract of Costus afer stems had no effects on strychnine-induced seizures at doses of 250 mg/kg and 500 mg/kg compared to the control group. However, the extract of Costus afer stems caused a very significant decrease in motricity at a dose of 500 mg/kg, showing a decrease in the onset time and a very significant increase in sleep duration like the reference molecule such as Diazepam. The aqueous extract of Costus afer stems also caused a decrease in immobility time in mice at a dose of 500 mg/kg.展开更多
In clinical trials, drug effect is measured by a difference between subjects who are treated by experimental drug against placebo-treated subjects. In case of binary data, with observing YES/NO on each subject in cert...In clinical trials, drug effect is measured by a difference between subjects who are treated by experimental drug against placebo-treated subjects. In case of binary data, with observing YES/NO on each subject in certain period of time, it is the proportion of subjects who respond in treatment group minus the proportion of responders in placebo group (for example, 50% vs. 30%). However, a greater difference was proposed by Rihmer et al. (2011) [1] with their supporting arguments, in that antidepressant response and placebo response had different mechanisms and there were equal chances for antidepressant responder to be responding to placebo and not responding to placebo at all. Therefore, the authors proposed 50% - 30% * 50% when the response rate in the treatment group and the placebo group are 50% and 30% respectively, resulting in higher drug-placebo difference than traditional understanding of 50% - 30%. In this article, we tried to explain why the authors misunderstood the drug-placebo concept for evaluating drug superiority, their misunderstanding of assumptions of traditional calculation, as well as their wrong reasoning on their proposed approach. All in all, we conclude the traditional approach of 50% - 30% is the right way of evaluating drug-placebo difference and the possible methods to control impact of placebo effect are briefly discussed at the end of this article.展开更多
Depressive disorder is a complex,heterogeneous disease that affects approximately 280 million people worldwide.Environmental,genetic,and neurobiological factors contribute to the depressive state.Since the nervous sys...Depressive disorder is a complex,heterogeneous disease that affects approximately 280 million people worldwide.Environmental,genetic,and neurobiological factors contribute to the depressive state.Since the nervous system is susceptible to shifts in activity of epigenetic modifiers,these allow for significant plasticity and response to rapid changes in the environment.Among the most studied epigenetic modifications in depressive disorder is DNA methylation,with findings centered on the brain-derived neurotrophic factor gene,the glucocorticoid receptor gene,and the serotonin transporter gene.In order to identify biomarkers that would be useful in clinical settings,for diagnosis and for treatment response,further research on antidepressants and alterations they cause in the epigenetic landscape throughout the genome is needed.Studies on cornerstone antidepressants,such as selective serotonin reuptake inhibitors,selective serotonin and norepinephrine reuptake inhibitors,norepinephrine,and dopamine reuptake inhibitors and their effects on depressive disorder are available,but systematic conclusions on their effects are still hard to draw due to the highly heterogeneous nature of the studies.In addition,two novel drugs,ketamine and esketamine,are being investigated particularly in association with treatment of resistant depression,which is one of the hot topics of contemporary research and the field of precision psychiatry.展开更多
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.
基金supported by the National Natural Science Foundation of China,No.81871070Jilin Province Medical and Health Talents,No.2020SCZT021Changchun City Science and Technology Development Plan Key Project,No.21ZGY16 (all to BJL)。
文摘Recent studies have shown that a 9-hour fast in mice reduces the amount of time spent immobile in the forced swimming test.Howeve r,whether 9-hour fasting has therapeutic effects in female mice with depressive symptoms has not been established.Therefore,in this study,we simulated perimenopausal depression via an ovariectomy in mice,and subjected them to a single 9-hour fasting 7 days later.We found that the ovariectomy increased the time spent immobile in the forced swimming test,inhibited expression of the mammalian target of rapamycin complex 1 signaling pathway in the hippocampus and prefro ntal cortex,and decreased the density of dendritic spines in the hippocampus.The 9-hour acute fasting alleviated the above-mentioned phenomena.Furthermore,all of the antidepressant-like effects of 9-hour fasting were reve rsed by an inhibitor of the mammalian to rget of rapamycin complex 1.Electrophysiology data showed a remarkable increase in long-term potentiation in the hippocampal CA1 of the ovariectomized mice subjected to fasting compared with the findings in the ovariectomized mice not subjected to fasting.These findings show that the antidepressant-like effects of 9-hour fasting may be related to the activation of the mammalian target of the rapamycin complex 1 signaling pathway and synaptic plasticity in the mammalian hippocampus.Thus,fasting may be a potential treatment for depression.
基金This project was supported by Natural Science Foundation of Henan Province of China(Grant No.232300420266).
文摘Depression,a prevalent mood disorder,has emerged as a significant health concern in society.While the exact cause of depression remains incompletely understood,there is substantial evidence linking the gastrointestinal microbiome and its metabolites to this condition.Through combined multi-omics analysis,it has been observed that the composition of the gastrointestinal microbiome,including Firmicutes,Bacteroidetes,and Actinobacteria,undergoes significant alterations in depressed individuals.Moreover,the production of short-chain fatty acids,tryptophan,and bile acids by these gut microbes is also found to be modified in depression.Furthermore,studies have demonstrated that antidepressant medications exert their therapeutic effects by interacting with the gastrointestinal microbiome and their metabolites.This review provides an overview of the association between the gastrointestinal microbiome,related metabolites,and depression.It highlights the potential of these factors to serve as mechanisms of action for antidepressant medications.Additionally,the review summarizes the commonly used technical tools in depression research.
基金funded by the Hebei Province Graduate Innovation Funding Project(HBU2023SS004)Baoding Science and Technology Planning Project(2341ZF145).
文摘QT interval prolongation can be categorized into primary and secondary types according to its etiology.In this paper,we report a case of severe asymptomatic QT interval prolongation secondary to antidepressants.Regular follow-up and electrocardiogram monitoring is crucial when applying antidepressants,especially for patients without cardiac symptoms.This article presents case studies and examines existing literature on long QT syndrome to enhance the diagnosis and management of QT interval prolongation.This is especially relevant for non-psychiatric healthcare professionals who need to be attentive to the side effects of antidepressants to prevent potential adverse consequences resulting from oversight.
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.
文摘The pathophysiology of depression has been traditionally attributed to a chemical imbalance and critical interactions between genetic and environmental risk factors, and antidepressant drugs suggested to act predominantly amplifying monoaminergic neurotransmission. This conceptualization may be currently considered reductive. The current literature about the pathophysiological mechanisms underlying depression, stress-related disorders and antidepressant treatment was examined. In order to provide a critical overview about neuroplasticity, depression and antidepressant drugs, a detailed Pubmed/Medline, Scopus, Psyc Lit, and Psyc Info search to identify all papers and book chapters during the period between 1980 and 2011 was performed. Pathological stress and depression determine relevant brain changes such as loss of dendritic spines and synapses, dendritic atrophy as well as reduction of glial cells(both in number and size) in specific areas such as the hippocampus and prefrontal cortex. An increased dendritic arborisation and synaptogenesis may instead be observed in the amygdala as a consequence of depression and stress-related disorders. While hippocampal and prefrontal functioning was impaired, amygdala functioning was abnormally amplified. Most of molecular abnormalities and biological changes of aberrant neuroplasticity may be explained by the action of glutamate. Antidepressant treatment is associated with neurogenesis, gliogenesis, dendritic arborisation, new synapse formation and cell survival both in the hippocampus and prefrontal cortex. Antidepressants(ADs) induce neuroplasticity mechanisms reversing the pathological effects of depression and stress-related disorders. The neuroplasticity hypothesis may explain the therapeutic and prophylactic action of ADs representing a new innovative approach to the pathophysiology of depression and stress-related disorders.
文摘Inflammatory bowel disease (IBD) is a group of inflammatory disorders mainly affecting the colon and small intestine. The main types of IBD are Crohn’s disease (CD) and ulcerative colitis (UC). UC is restricted to the large intestine whereas CD can affect any part of the gastrointestinal tract. Treating this disorder depends on the form and level of severity. Common treatment involves an anti-inflammatory drug, such as mesalazine, and an immunosuppressant, such as prednisone. Several signaling pathways, including nuclear factor (NF)-κB and nitric oxide (NO), and genetic and environmental factors are believed to play an important role in IBD. Amitriptyline is a commonly used antidepressant with known anti-inflammatory activities. Amitriptyline also acts on the NF-κB/NO pathway or cytokine production. Therefore, we hypothesize that antidepressants like amitriptyline can be pioneered and considered effective as an innovative and effective therapeutic in the treatment and attenuation of development of IBD in adjusted doses.
基金Authors are thankful to Director,CSMCRI,Bhavnagar for pro-viding necessary infrastructure facilities and the Council of Scientific and Industrial Research,Government of India,New Delhi,India(CSIR)for Senior research fellowship awarded to BDK,and funding under Network Project:NWP 0010.
文摘This work evaluates intercalation of Nortriptyline(NT)and Venlafaxine(VFX)in an interlayer gallery of Na^(+)-MMT(Montmorillonite),which was further compounded with Poly(LLactide)(PLLA)to form microcomposite spheres(MPs)for oral controlled drug delivery.The XRD patterns,thermal and spectroscopic analyses indicated intercalation of drugs into the MMT interlayer that was stabilized by electrostatic interaction.No significant changes in structural and functional properties of drugs were found in the MMT layers.In vitro drug release studies showed controlled release pattern.
文摘Objective:Acorus calamus(AC)L.(Araceae)is an annual semi-aquatic and aromatic plant found in Europe,North America and Asia.Its rhizomes are often used by Native Americans,Americans,and Chinese as well as by other cultures.Ethnobotanical studies and documents have shown their use in various disease treatments,such as insomnia,mental disorders,diabetes mellitus,epilepsy,inflammation,asthma,neuropathic pain,and diarrhea.In this study,the antidepressant activity of methanolic and hydroalcoholic extracts of the AC rhizome part in mice was investigated.Methods:Three doses of methanolic extract of AC rhizome(MEACR)(25,50 and 100 mg/kg b.wt),three doses of hydroalcoholic extract of AC rhizome(HAACR)(100,200 and 400 mg/kg b.wt),and standards(imipramine,15 mg/kg b.wt and fluoxetine,20 mg/kg b.wt)was daily oral administration to the mice for consecutive 14 days.The extract effect on the immobility time was monitored by a tail suspension test(TST)and a forced swimming test(FST).Monoamine oxidase(MAO)levels were also analyzed using standard methods.Results:The optimum antidepressant activity was viewed at 100 mg/kg b.wt of MEACR extract and400 mg/kg b.wt of HAACR extract with 23.82%and 20.59%immobility period reduction,respectively.Besides,the extracts weakened the FST-induced elevation of MAO activity significantly and returned to near-normal levels of neurotransmitters in the brain.100 mg/kg b.wt or above of MEACR extract significantly prevented the MAO-A and MAO-B activities in mice brain at a dose-dependent fashion.But,just 400 mg/kg b.wt of HAACR extract prevented the activity of MAO-A and MAO-B.Fluoxetine and imipramine showed a tendency to prevent the activity of MAO-A and MAO-B.Conclusion:This study suggests that AC rhizome extract mediated antidepressant activity by modulating the central neurochemical and hypothalamic-pituitary-adrenal(HPA)axis in response to FST and TSTinduced stress.Therefore,AC rhizome extract can be used as a valuable plant supplement to treat depressive disorders.
文摘Objective: Although antidepressants are the recommended first-line pharmacological treatments for depressive and anxiety disorders, their prescribing patterns have not been studied in Singapore. We investigate antidepressant prescription patterns for outpatients with depressive and anxiety disorders in a general hospital in Singapore. We hypothesize that intolerance to side effects and lack of efficacy may contribute to medication switching, and that initiation of antidepressant therapy is not easily tolerated. Methods: A retrospective review of the casenotes of outpatients was carried out between January 2013 and December 2013. A total of 206 patients were randomly selected. The study was approved by the hospital’s institutional review board. Data analysis was carried out using SPSS version 18. Results: There were more females than males (ratio 1.7:1) with a mean age of 50.6 ± 15.2 years. Depressive disorder, comprising 50% of the sample, was the most frequent diagnosis followed by anxiety disorder (27.2%), mixed anxiety-depression (16%) and adjustment disorder (5.8%). Almost all patients (97.1%) were prescribed antidepressants, the most common being selective serotonin reuptake inhibitors (SSRI) (75.5%), followed by the noradrenaline and specific serotonin antidepressant (NaSSA) (13.5%) and tricyclic antidepressants (TCA) (8.5%). Patients prescribed SSRIs tended to be younger and better educated (p = 0.0005). More than half of the patients (52.1%) required antidepressant switching mainly due to lack of efficacy and intolerance of side effects. Combination therapy was prescribed for 17% of patients with SSRI-NaSSA, the most preferred combination. Nearly a quarter (23.8%) patients required augmentation therapy with atypical antipsychotics. Combination (p = 0.024) and augmentation (p = 0.033) were utilized more often for depression than for anxiety disorders. Conclusion: Antidepressant medications are commonly prescribed for depression and anxiety disorders. The main reasons for switching antidepressants were intolerance and lack of efficacy. That about half of the patients reported side effects necessitating medication change confirmed our hypothesis that antidepressant therapy was not easy to initiate. This has important implications for treatment adherence and outcome.
基金Supported by the Conselho Nacional de Desenvolvimento Científico e Tecnológico,No.310113/2017-2the CNPq Research Productivity Fellowship.
文摘Major depressive disorder(MDD)is a disabling and highly prevalent mood disorder as well as a common cause of suicide.Chronic stress,inflammation,and intestinal dysbiosis have all been shown to play crucial roles in the pathophysiology of MDD.Although conventional antidepressants are widely used in the clinic,they can take weeks to months to produce therapeutic effects.The discovery that ketamine promotes fast and sustaining antidepressant responses is one of the most important breakthroughs in the pharmacotherapy of MDD.However,the adverse psychomimetic/dissociative and neurotoxic effects of ketamine discourage its chronic use.Therefore,agmatine,an endogenous glutamatergic modulator,has been postulated to elicit fast behavioral and synaptogenic effects by stimulating the mechanistic target of rapamycin complex 1 signaling pathway,similar to ketamine.However,recent evidence has demonstrated that the modulation of the NLR family pyrin domain containing 3 inflammasome and gut microbiota,which have been shown to play a crucial role in the pathophysiology of MDD,may also participate in the antidepressant-like effects of both ketamine and agmatine.This review seeks to provide evidence about the mechanisms that may underlie the fast antidepressant-like responses of agmatine in preclinical studies.Considering the anti-inflammatory properties of agmatine,it may also be further investigated as a useful compound for the management of MDD associated with a pro-inflammatory state.Moreover,the fast antidepressant-like response of agmatine noted in animal models should be investigated in clinical studies.
基金National Natural Science Foundation of China(3120077181030065+5 种基金8127405531371066013117101101)Ministry of Science and Technology(2013CB91060101)National Science Technology Major Project of China (2012ZX09301-001-062014ZX09102001-005).
文摘OBJECTIVE To find that the extracellular cap of a K2P channel can act as a new allosteric site and may serve as a direct drug target.METHODS Molecular biology and cell transfection,electrophysiology,molecular docking,molecular dynamics simulations,virtual screening for TREK1,and depressive-related behavior tests.RESULTS Extracellular domain of TREK1 channel existed a dynamic cavity in the extracellular domain by the method of computations,mutagenesis and electrophysiology.Molecular dynamics simulations suggested that ligand-induced allosteric conformational transitions lead to blockage of the ion conductive pathway.Using virtual screening approach,we identified other inhibitors targeting the extracellular allosteric ligand-binding site of these channels.Overall,our results suggested that the allosteric site at the extracellular cap of the K2P channels might be a promising drug target for these membrane proteins.The TREK1 inhibitor TKDC had significantly faster onset than that of fluoxetine in chronic administration trials,and the study confirms that TREK1 was an important target for the development of rapid antidepressants.CONCLUSION The study is a significant step forward for understanding the function of TREK and for identifying specific inhibitors,which should be of interest to others in the field.
文摘Medicinal plants and their ingredients have beneficial effects on human health.Nigella sativa is a herbal plant with multiple biological and pharmacological activities.Previous studies demonstrated the anti-inflammatory and antioxidant properties of Nigella sativa and its main constituent thymoquinone significantly contributes to the antidepressant and anti-nociception effects of this plant.It has been reported that thymoquinone may achieve its antidepressant effect by preventing the elimination of brain neurotransmitters affecting depression such as serotonin.The role of brain-derived neurotrophic factors in the antidepressant effects of thymoquinone has also been documented.Additionally,thymoquinone can attenuate pain by upregulation of intracellular signaling pathways related to nitric oxide and K_(ATP)^(+)channels.The present review summarizes the antidepressant and anti-nociceptive activity of Nigella sativa and its main constituent thymoquinone by searching literature on electronic databases such as PubMed,Web of Science,Scopus,and Google Scholar from the beginning of 2010 until the end of August 2022.
文摘OBJECTIVE Phosphodiesterase 4(PDE4),specific for cyclicAMP(cAMP)-hydrolyzing,has four isoforms(PDE4A-D) with at least 25 splice variants. PDE4 inhibitors produce definite antidepressant-like and cognitive-enhancing effects. However,none of PDE4 inhibitors has yet been approved for clinical utility so far due to the concomitant side effects. The present research is to explore the splice variants of PDE4 D responsible for antidepressant-like and cognitive-enhancing effects of PDE4 inhibitors but not side effects. METHODS Long-form PDE4 Ds were silenced by the bilateral microinfusion of lentiviral vector containing mi RNAs(4Dmi R) into the prefrontal cortex(PFC),PDE4D4 or D5 was overexpressed by the bilateral microinfusion of lentiviral vector containing full c DNA into hippocampus. Antidepressant-like behaviors were measured by tail-suspension test(TST),forced swimming test(FST)and chronic unpredictable stress model. Cognitive behaviors were measured by the novel object recognition test(NOR) and Morris water maze test(MWM) in both normal mice and the mice with chronic unpredictable stress-induced memory deficits. The emetic potential was evaluated by the assessment of the anaesthetic reversal effect,a surrogate of the emesis test in non-vomiting species. The expressions of PDE4 isoforms/splice variants and cAMP level were examined by Western-blot and ELISA analysis. The dendritic complexity and spine density were assessed by Golgi staining. RESULTS(1)High and specific expression of EGFP(green,indicator of 4Dmi R expression) in PFC was observed under fluorescence microscopy.(2) 4Dmi R significantly down-regulated PDE4D4/5 splice variants,but not PDE4 A,PDE4 B or PDE4D1/2/3.(3) 4Dmi R treatments significantly increased cAMP signaling and dendritic complexity in PFC.(4) Rolipram and/or 4Dmi R treatments significantly decreased immobility in TST and FST.(5) Rolipram and/or 4Dmi R treatments reversed the depressive-like behaviors in chronically stressed mice,including the reduced sucrose preference,prolonged latency to novelty-suppressed feeding and increased immobility in FST.(6) Rolipram and/or 4Dmi R treatments significantly increased the recognition index in NOR task and both the entries and durations in MWM task.(7) Rolipram and/or 4Dmi R treatments reversed the memory deficits in chronically stressed mice,including the reduced the recognition index in NOR task and the decreased durations in MWM task.(8) Rolipram and/or 4DmiR treatments reversed the decreased cA MP signaling,dendritic complexity and spine density.(9) Rolipram or plus 4Dmi R treatment significantly decreased the duration of anaesthesia in the alpha2 adrenergic receptor-mediated anesthesia,but not 4Dmi R treatment alone.(10)Hippocampal overexpression of PDE4D5,but not PDE4D4,produced depressive-like and cognitive defect behaviors,which were reversed by rolipram.The measurements including cAMP signaling,dendritic complexity and in vivo hippocampal LTP,showed the same changes. CONCLUSION Long-form PDE4 Ds,especially the PDE4D5,are the major isoforms responsible for antidepressant-like and cognitive-enhancing effects with little side effects. The critical roles of long-form PDE4 Ds are mediated by their regulation of cAMP signaling pathway and neuroplasticity.
文摘Currently, accumulating studies indicated that upregulation of glycogen synthase kinase-3β （GSK3β） played an important role in depression pathogenesis. Our previous study demonstrated that ammoxetine, a novel se- rotonin and norepinephrine uptake inhibitor, displayed antidepressant activity more potent and faster than existing antidepressants, which may be clue to the increasing of hippocampal inhibitory serine-phosphorylation of glycogen synthase kinase-3 （GSK3）. The present study was to evaluate whether activation of PI3K/Akt signaling, one of the most important pathways regulating the phosphorylation of GSK3β, was required for ammoxetine induced antide- pressant effects and upregulation of pGSK3β. Behavioral results indicated that acute oral administration of ammoxe- tine at 10 mg/kg produced robust antidepressant effects in the forced swimming test and learned helpless test in mice, which were blocked totally by phosphatidylinositol （PI3）-kinase （PI3K） inhibitor LY294002. Then, West- ern blot results demonstrated that ammoxetine induced increasing of GSK3 β phosphorylation and activation of PI3 K/ Akt signaling can also be antagonized at the same testing time points by LY294002. These findings suggest that ac- tivation of PI3 K/Akt/GSK3[3 signaling is pivotal and necessary for the antidepressant effects of ammoxetine in the forced swimming test and learned helpless test in mice.
基金the Construction Plan of Scientific Research and Innovation Team of Colleges and Universities in Sichuan Province(18TD0017)Xinglin Scholar Research Promotion Project of Chengdu University of TCM(CXTD2018018)。
文摘[Objectives]To study the content and antidepressant effects of the flavonoids in the Zanthoxylum Pericarpium Residue(ZPR)and to provide a basis for the full utilization of ZPR.[Methods]The method for the assay of total flavonoids in ZPR by UV spectrophotometry was developed with rutin as reference.The total flavonoids were extracted and separated from ZPR.The contents of total flavonoids were quantified in ZPR and its extract.The autonomous activity test,tail suspension test and forced swimming test were conducted in mice,and the levels of malondialdehyde(MDA),superoxide dismutase(SOD)and total antioxidation were detected to evaluate the antidepressant effects of total flavonoids.[Results]The recovery rate of UV spectrophotometry was 98.88%(n=6).The contents of flavonoids in ZPR and its extract were 11.07%and 78.42%,respectively.In the autonomous activity test,compared with the control group,the standing times of mice in the positive drug group was significantly increased(P<0.05),but there was not significant difference among the low-,medium-and high-dose groups of total flavonoids extract(P>0.05),as well as there was no significant difference of the activity times among all groups(P>0.05).In the tail suspension and forced swimming tests,compared with the control group,the immobility time of the high-dose group of total flavonoids extract was significantly reduced(P>0.05),and the serum SOD levels of the low-,medium-and high-dose groups were significantly increased(P<0.05).The MDA levels of the middle-and high-dose groups of total flavonoids were significantly decreased(P<0.05),and the total antioxidant capacity was increased significantly(P<0.05).[Conclusions]The developed UV spectrophotometry can accurately detect the level of total flavonoids in ZPR.ZPR is rich in flavonoids,and has significant antidepressant effects,which may be related to eliminating internal free radicals and inhibiting lipid peroxidation.
文摘The role played by serendipity in the origin of modern psychopharmacology has proven to be controversial in scientific literature.In its original meaning(Walpole),serendipity refers to discoveries made through a combination of accidents and sagacity.We have implemented an operational definition of serendipity based on finding something unexpected or unintended,regardless of the systematic process that led to the accidental observation,and we have established four different patterns of serendipitous attributability.In this paper,we have analyzed the role of serendipity in the discovery and development of classical antidepressant drugs,tricyclic antidepressants and monoamine oxidase inhibitors as well as heterocyclic,“atypical”or“second generation”antidepressants.The discovery of the antidepressant properties of imipramine and iproniazid,the prototypes of tricyclic antidepressants and monoamine oxidase inhibitors,respectively,fits the mixed type II pattern;initial serendipitous discoveries(imipramine was an antipsychotic and iproniazid was an antituberculosis agent)led secondarily to non-serendipitous discoveries.But the other components of these two families of drugs were developed specifically as antidepressants,modifying the chemical structure of the series leaders,thereby allowing all of them to be included in the type IV pattern,characterized by the complete absence of serendipity.Among the heterocyclic drugs,mianserin(originally developed as an antihistamine)also falls into the type II pattern.
文摘Epilepsy is a disorder in the nervous system which often causes a loss of consciousness. Traditional treatments are quiet a component of health care system in various populations in spite of the fact that well-established options are available. Most plants are used to treat epilepsy or those which have been verified for anticonvulsant activity were reported. Then, Costus afer is a plant of the Congolese flora used in traditional medicine for its many virtues. Therefore, the anticonvulsant activity of Costus afer was assessed with the strychnine convulsion induction test. Two tests were used for sedative activity such as the barbiturate sleep induction test and motor activity and finally the forced swimming test was also used to assess antidepressant activity. The results showed that the aqueous extract of Costus afer stems had no effects on strychnine-induced seizures at doses of 250 mg/kg and 500 mg/kg compared to the control group. However, the extract of Costus afer stems caused a very significant decrease in motricity at a dose of 500 mg/kg, showing a decrease in the onset time and a very significant increase in sleep duration like the reference molecule such as Diazepam. The aqueous extract of Costus afer stems also caused a decrease in immobility time in mice at a dose of 500 mg/kg.
文摘In clinical trials, drug effect is measured by a difference between subjects who are treated by experimental drug against placebo-treated subjects. In case of binary data, with observing YES/NO on each subject in certain period of time, it is the proportion of subjects who respond in treatment group minus the proportion of responders in placebo group (for example, 50% vs. 30%). However, a greater difference was proposed by Rihmer et al. (2011) [1] with their supporting arguments, in that antidepressant response and placebo response had different mechanisms and there were equal chances for antidepressant responder to be responding to placebo and not responding to placebo at all. Therefore, the authors proposed 50% - 30% * 50% when the response rate in the treatment group and the placebo group are 50% and 30% respectively, resulting in higher drug-placebo difference than traditional understanding of 50% - 30%. In this article, we tried to explain why the authors misunderstood the drug-placebo concept for evaluating drug superiority, their misunderstanding of assumptions of traditional calculation, as well as their wrong reasoning on their proposed approach. All in all, we conclude the traditional approach of 50% - 30% is the right way of evaluating drug-placebo difference and the possible methods to control impact of placebo effect are briefly discussed at the end of this article.
基金Supported by Slovenina Reserach Agency,Young Researcher Grant to I?,No.P1-0390。
文摘Depressive disorder is a complex,heterogeneous disease that affects approximately 280 million people worldwide.Environmental,genetic,and neurobiological factors contribute to the depressive state.Since the nervous system is susceptible to shifts in activity of epigenetic modifiers,these allow for significant plasticity and response to rapid changes in the environment.Among the most studied epigenetic modifications in depressive disorder is DNA methylation,with findings centered on the brain-derived neurotrophic factor gene,the glucocorticoid receptor gene,and the serotonin transporter gene.In order to identify biomarkers that would be useful in clinical settings,for diagnosis and for treatment response,further research on antidepressants and alterations they cause in the epigenetic landscape throughout the genome is needed.Studies on cornerstone antidepressants,such as selective serotonin reuptake inhibitors,selective serotonin and norepinephrine reuptake inhibitors,norepinephrine,and dopamine reuptake inhibitors and their effects on depressive disorder are available,but systematic conclusions on their effects are still hard to draw due to the highly heterogeneous nature of the studies.In addition,two novel drugs,ketamine and esketamine,are being investigated particularly in association with treatment of resistant depression,which is one of the hot topics of contemporary research and the field of precision psychiatry.
