Analysis of Antidepressant Quality Markers of Bupleuri Radix Before and After Vinegar-processing Based on UPLC-Q-TOF-MS and Network Pharmacology / 中国实验方剂学杂志

ObjectiveTo analyze the antidepressant quality markers（Q-Marker） of Bupleuri Radix（BP） before and after vinegar-processing by ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS）， multivariate statistical analysis and network pharmacology. MethodUPLC-Q-TOF-MS was used to analyze the chemical basis of raw and vinegar-processed products of BP， and principal component analysis（PCA） orthogonal partial least squares-discriminant analysis（OPLS-DA） were used to identify the differential components in BP that changed significantly before and after vinegar-processing， which were regarded as candidate quality markers（Q-Marker）. Then the disease-drug-component-target network related to antidepressant effect of BP was constructed by network pharmacology， and the antidepressant Q-Marker of raw and vinegar-processed products of BP was determined. Rats were randomly divided into blank group， model group， fluoxetine group（2.67 mg·kg-1） and total saponin group（0.72 mg·kg-1）， except the blank group， rats in the other groups were subjected to chronic unpredictable mild stress（CUMS）. Three weeks after the start of modeling， rats in each administration group were given the corresponding dose of drugs once a day for 4 weeks， and rats in the blank and model groups were given normal saline with dose of 10 mL·kg-1. At 1 day before modeling， 21 days and 28 days after administration， body mass weighing， sucrose preference test and open field test were performed on each group . After 28 days of administration， real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） was used to detect the mRNA expression levels of phosphatidylinositol 3-kinase（PI3K）， protein kinase B（Akt）， mammalian target of rapamycin（mTOR）， glycogen synthase kinase-3β（GSK-3β）， forkhead box transcription factor O3a（FoxO3a） and β-catenin in hippocampal tissues of rats in each group， while protein expression levels of PI3K， Akt， mTOR and FoxO3a in hippocampal tissues of rats in each group were detected by Western blot. ResultThere were 19 components in BP showed significant changes before and after vinegar-processing， and 9 components such as saikosaponin A， saikosaponin B1， saikosaponin B2， saikosaponin C and saikosaponin D were identified as potential Q-Marker through S-plot differential marker screening. Combined with the disease-drug-component-target network， saikosaponin A， saikosaponin B1， saikosaponin B2 and saikosaponin D were identified as antidepressant Q-Marker of raw and vinegar-processed products of BP. According to the results of pharmacodynamic tests， after 28 d of administration， compared with the blank group， the body mass， sucrose preference index and open field total score of rats in model group， fluoxetine group and total saponin group decreased significantly（P<0.01）. Compared with the model group， the body mass， sucrose preference index and open field total score in total saponin group increased significantly（P<0.01）. Compared with the blank group， mRNA expression levels of PI3K， Akt， mTOR and β-catenin in hippocampus of rats in the model group decreased significantly（P<0.05）， while mRNA expression levels of GSK-3β and FoxO3a increased significantly（P<0.05）. Compared with the model group， mRNA expression levels of PI3K， Akt， mTOR and β-catenin in hippocampus of rats in the total saponin group were increased significantly（P<0.05）， while mRNA expression levels of GSK-3β and FoxO3a decreased significantly（P<0.05）. Compared with the blank group， the protein expression levels of Akt and mTOR in hippocampus of the model group decreased significantly（P<0.01）， while the protein expression levels of PI3K and FoxO3a increased significantly（P<0.01）. Compared with the model group， the expression level of Akt in hippocampus of the total saponin group increased significantly（P<0.01）， the mTOR expression level was increased but not statistically significant， while the protein expression levels of PI3K and FoxO3a decreased significantly（P<0.01）. ConclusionThe chemical constituents of BP changed greatly after vinegar-processing， and the antidepressant Q-Marker of raw and vinegar-processed products of BP was determined by chemical basis， pharmacodynamics， network pharmacology and signaling pathway， which provided a reference for further research on quality control， pharmacodynamic substance basis and processing mechanism of BP.

A new suberin from roots of Ephedra sinica Stapf / 药学学报

Six compounds were isolated from the roots of Ephedra sinica Stapf using various chromatographic techniques such as silica gel column chromatography, thin layer chromatography and semi-preparative HPLC. Their chemical structures were identified by analysis of physicochemical properties and spectral data, and determined as (Z)-docosanylferulate (1), (E)-docosanylferulate (2), bis (2-ethylheptyl) phythalate (3), 2,2′-oxybis (1,4-di-tert-butylbenzene) (4), diisobutyl phthalate (5), bis (2-ethylhexyl) phthalate (6). Among them, compound 1 is a new compound, compounds 2-4 were first isolated from Ephedra. A corticosterone-induced PC-12 cell injury model was used for compound activity screening. The results showed that compounds 1 and 5 significantly improved corticosterone-induced PC-12 cell injury and significantly increased 5-HT7 receptor protein expression in the cells, indicating potential antidepressant activity.

Targeting cAMP in D1-MSNs in the nucleus accumbens, a new rapid antidepressant strategy

Studies have suggested that the nucleus accumbens (NAc) is implicated in the pathophysiology of major depression; however, the regulatory strategy that targets the NAc to achieve an exclusive and outstanding anti-depression benefit has not been elucidated. Here, we identified a specific reduction of cyclic adenosine monophosphate (cAMP) in the subset of dopamine D1 receptor medium spiny neurons (D1-MSNs) in the NAc that promoted stress susceptibility, while the stimulation of cAMP production in NAc D1-MSNs efficiently rescued depression-like behaviors. Ketamine treatment enhanced cAMP both in D1-MSNs and dopamine D2 receptor medium spiny neurons (D2-MSNs) of depressed mice, however, the rapid antidepressant effect of ketamine solely depended on elevating cAMP in NAc D1-MSNs. We discovered that a higher dose of crocin markedly increased cAMP in the NAc and consistently relieved depression 24 h after oral administration, but not a lower dose. The fast onset property of crocin was verified through multicenter studies. Moreover, crocin specifically targeted at D1-MSN cAMP signaling in the NAc to relieve depression and had no effect on D2-MSN. These findings characterize a new strategy to achieve an exclusive and outstanding anti-depression benefit by elevating cAMP in D1-MSNs in the NAc, and provide a potential rapid antidepressant drug candidate, crocin.

Genotoxic and cytotoxic evaluation of venlafaxine in an acute and a subchronic assay in mouse

Abstract The present research was made to determine the micronuclei and cytotoxic capacity of the antidepressant venlafaxine in an in vivo acute and subchronic assays in mouse. In the first study, we administered once 5, 50, and 250 mg/kg of the drug, and included a negative and a daunorubicin treated group. Observations were daily made during four days. The subchronic assay lasted 5 weeks with daily administration of venlafaxine (1, 5, and 10 mg/kg) plus a negative and an imipramine administered groups. Observations were made each week. In the first assay results showed no micronucleated polychromatic erythrocytes (MNPE) increase, except with the high dose at 72 h. The strongest cytotoxic effect was found with 250 mg/kg at 72 h (a 51% cytotoxic effect in comparison with the mean control level). In the subchronic assay no MNPE increase was found; however, with the highest dose a significant increase of micronucleated normochromatic erythrocytes was observed in the last three weeks (a mean of 51% respect to the mean control value). A cytotoxic effect with the two high doses in the last two weeks was observed (a polychromatic erythrocyte mean decrease of 52% respect to the mean control value). Results suggest caution with venlafaxine.

Resumo A presente pesquisa foi feita para determinar a capacidade micronuclei e citotóxica do antidepressivo venlafaxina em ensaios agudos e subcrônicos in vivo em camundongos. No primeiro estudo, administramos uma vez 5, 50 e 250 mg/kg do medicamento e incluímos um grupo negativo e um grupo tratado com daunorubicina. As observações foram feitas diariamente durante quatro dias. O ensaio subcrônico durou cinco semanas com administração diária de venlafaxina (1, 5, e 10 mg/kg) mais um grupo negativo e um grupo administrado de imipramina. As observações foram feitas a cada semana. No primeiro ensaio, os resultados não mostraram aumento de eritrócitos policromáticos micronucleados (MNPE), exceto com a dose elevada a 72 h. O efeito citotóxico mais forte foi encontrado com 250 mg/kg a 72 h (um efeito citotóxico de 51% em comparação com o nível médio de controle). No ensaio subcrônico não foi encontrado aumento de MNPE; entretanto, com a dose mais alta, um aumento significativo de eritrócitos normocromáticos micronucleados foi observado nas últimas três semanas (média de 51% em relação ao valor médio de controle). Foi observado um efeito citotóxico com as duas altas doses nas últimas duas semanas (uma diminuição média de 52% em relação ao valor médio de controle dos eritrócitos policromáticos). Os resultados sugerem cautela com a venlafaxina.

Genotoxic and cytotoxic evaluation of venlafaxine in an acute and a subchronic assay in mouse / Avaliação genotóxica e citotóxica da venlafaxina em ensaio agudo e subcrônico em camundongos

Abstract The present research was made to determine the micronuclei and cytotoxic capacity of the antidepressant venlafaxine in an in vivo acute and subchronic assays in mouse. In the first study, we administered once 5, 50, and 250 mg/kg of the drug, and included a negative and a daunorubicin treated group. Observations were daily made during four days. The subchronic assay lasted 5 weeks with daily administration of venlafaxine (1, 5, and 10 mg/kg) plus a negative and an imipramine administered groups. Observations were made each week. In the first assay results showed no micronucleated polychromatic erythrocytes (MNPE) increase, except with the high dose at 72 h. The strongest cytotoxic effect was found with 250 mg/kg at 72 h (a 51% cytotoxic effect in comparison with the mean control level). In the subchronic assay no MNPE increase was found; however, with the highest dose a significant increase of micronucleated normochromatic erythrocytes was observed in the last three weeks (a mean of 51% respect to the mean control value). A cytotoxic effect with the two high doses in the last two weeks was observed (a polychromatic erythrocyte mean decrease of 52% respect to the mean control value). Results suggest caution with venlafaxine.

Resumo A presente pesquisa foi feita para determinar a capacidade micronuclei e citotóxica do antidepressivo venlafaxina em ensaios agudos e subcrônicos in vivo em camundongos. No primeiro estudo, administramos uma vez 5, 50 e 250 mg/kg do medicamento e incluímos um grupo negativo e um grupo tratado com daunorubicina. As observações foram feitas diariamente durante quatro dias. O ensaio subcrônico durou cinco semanas com administração diária de venlafaxina (1, 5, e 10 mg/kg) mais um grupo negativo e um grupo administrado de imipramina. As observações foram feitas a cada semana. No primeiro ensaio, os resultados não mostraram aumento de eritrócitos policromáticos micronucleados (MNPE), exceto com a dose elevada a 72 h. O efeito citotóxico mais forte foi encontrado com 250 mg/kg a 72 h (um efeito citotóxico de 51% em comparação com o nível médio de controle). No ensaio subcrônico não foi encontrado aumento de MNPE; entretanto, com a dose mais alta, um aumento significativo de eritrócitos normocromáticos micronucleados foi observado nas últimas três semanas (média de 51% em relação ao valor médio de controle). Foi observado um efeito citotóxico com as duas altas doses nas últimas duas semanas (uma diminuição média de 52% em relação ao valor médio de controle dos eritrócitos policromáticos). Os resultados sugerem cautela com a venlafaxina.

Improvement of hedonic perception of odors as a marker of treatment response to escitalopram: olfactory changes through an open-label antidepressant trial

Objectives: To assess olfactory functions (threshold, identification, and hedonic valence) of depressed subjects before and after an 8-week trial of escitalopram and compare the results of responders and nonresponders. Methods: Fifty-two depressed subjects were recruited. Participants received escitalopram and were evaluated at two visits: baseline (V0) and week 8 (V8). They were categorized as responders (Montgomery-Åsberg Depression Rating Scale [MADRS] score reduction of > 50%) or nonresponders to treatment. Participants were evaluated with the Mini International Neuropsychiatric Interview (MINI) at V0 and, at V0 and V8, completed psychometric and olfactory assessments, including MADRS and the State-Trait Anxiety Inventory (STAI), as well as the Sniffin' Sticks® test (threshold and identification tasks). The hedonic valence of smell was assessed on a 10-cm linear scale after presenting two pleasant and two unpleasant odors. Forty-three participants completed the study (24 responders and 19 nonresponders). The Mann-Whitney, chi-square, and Fisher's exact tests were used to compare olfactory, clinical, and demographic variables between groups and within the same group at V0 and V8. The Spearman coefficient was used to calculate the correlation between clinical characteristics and olfactory variables. Results: The hedonic score of pleasant odors increased significantly between V0 and V8 only for responders (V = 61.5, p = 0.018), with no significant change in nonresponders (V = 90.5, p = 0.879). Comparison of olfactory performances between groups at V0 and V8 separately did not show a significant difference between responders and nonresponders to escitalopram. Olfactory threshold and identification scores were not different between V0 and V8 for responders or nonresponders. Conclusion: Depressed subjects have olfactory anhedonia, which appears to regress following a positive antidepressant response. Hedonic valence may be an indicator of cognitive changes associated with depression; improvement of this valence may indicate a clinical response to antidepressants.

Medicamentos antidepressivos estão associados a um risco aumentado de infecção hospitalar por Clostridioides difficile: um estudo populacional / Antidepressant medications are associated with increased risk of hospital-acquired clostridioides difficile infection: a population-based study

ABSTRACT Background: During the past decade, Clostridioides difficile infection (CDI) has become the most common cause of antibiotic-associated diarrhea. Several risk factors have been implicated. Scattered evidence about the association of CDI with antidepressant medications use exists in the literature so far. Therefore, we aim to investigate whether the risk of developing CDI is increased in hospitalized patients using antidepressant medications. Methods: Patients who were hospitalized were included in our cohort. We excluded individuals aged less than 18 years. A multivariate regression analysis was performed to calculate the risk of CDI accounting for potential confounders. Results: The risk of CDI in hospitalized patients was increased in individuals diagnosed with inflammatory bowel disease (OR: 4.44; 95%CI: 4.35-4.52), and in patients using clindamycin (OR: 1.55; 95%CI: 1.53-1.57), beta-lactam antibiotics (OR: 1.62; 95%CI: 1.60-1.64), PPI (OR: 3.27; 95%CI: 3.23-3.30), trazodone (OR: 1.31; 95%CI: 1.29-1.33), nortriptyline (OR: 1.25; 95%CI: 1.21-1.28), and mirtazapine (OR: 2.50; 95%CI: 2.46-2.54). After controlling for covariates, the risk of CDI was not increased in patients who were taking fluoxetine (OR: 0.94; 95%CI: 0.92-0.96). Conclusion: In contrary to fluoxetine; mirtazapine, nortriptyline, and trazodone were associated with increased risk of CDI in hospitalized patients.

RESUMO Contexto: Na última década, a infecção por Clostridioides difficile (ICD) tornou-se a causa mais comum de diarreia associada a antibióticos. Vários fatores de risco foram implicados. Existem evidências dispersas na literatura sobre a associação da ICD com o uso de medicamentos antidepressivos. Portanto, pretendemos investigar se o risco de desenvolver infecção adquirida na comunidade por Clostridioides difficile aumenta em pacientes que usam medicamentos antidepressivos. Métodos: Pacientes que foram hospitalizados foram incluídos em nossa coorte. Indivíduos com menos de 18 anos foram excluídos. Uma análise de regressão multivariada foi realizada para calcular o risco de ICD, considerando possíveis confusões. Resultados: O risco de ICD em pacientes hospitalizados foi maior em indivíduos diagnosticados com doença inflamatória intestinal (OR: 4,44; IC95%: 4,35-4,52) e em pacientes que usavam clindamicina (OR: 1,55; IC95%: 1,53-1,57), antibióticos beta-lactâmicos (OR: 1,62; IC95%: 1,60-1,64), PPI (OR: 3,27; IC95%: 3,23-3,30), trazodona (OR: 1,31; IC95%: 1,29-1,33), nortriptilina (OR: 1,25; IC95%: 1,21-1,28) e mirtazapina (OR: 2,50; IC95%: 2,46-2,54). Depois de controlar as covariáveis, o risco de ICD não aumentou em pacientes que estavam tomando fluoxetina (OR: 0,94; IC95%: 0,92-0,96). Conclusão: Em contrário à fluoxetina; mirtazapina, nortriptilina e trazodona foram associados a um risco aumentado de ICD em pacientes hospitalizados.

The Resurgence of Hallucinogen Drugs in Clinical Research

ABSTRACT Since the dawn of civilization, ancient cultures have utilized hallucinogens from plants and fungi in the context of religious and healing practices. Recently, their use has expanded to other cultures. Hallucinogens are natural or synthetic substances that alter the perception of reality at nontoxic doses, producing intense psychological and physiological effects. The initial research on hallucinogens began in the 1950s. However, their non-medical use, studies without proper controls, and negative social opinion resulted in legal restrictions that limited their use for clinical and preclinical research for more than two decades. A renewed interest in studying hallucinogens as potential therapeutic agents for treating different psychiatric conditions has recently re-emerged. This review summarizes the effects of main hallucinogen drugs and their therapeutic potential. Classic hallucinogens such as LSD, dimethyltryptamine, psilocin, and mescaline have chemical structures similar to serotonin and directly activate 5-hydroxy-tryptamine (5-HT2A) receptors. Ketamine is a dissociative anesthetic with antagonist effects at the glutamatergic N-methyl-D-aspartate receptor, indirectly activating 5-HT2A receptors. Ketamine has rapid antidepressant effects and reduces suicidal ideation, but its effects are short-lasting. Other hallucinogens are under study. It is necessary to continue this research with a more rigorous methodology and include studying the long-term effects of psychedelics use.

Intoxicación por antidepresivos tricíclicos / Tricyclic antidepressant poisoning

Introducción: el paciente intoxicado sigue siendo un desafío para el personal de salud. La intoxicación por antidepresivos tricíclicos (ATC) es un diagnóstico frecuente y una patología que puede llegar a ser muy grave. A pesar de que ha cambiado el objetivo terapéutico de estos fármacos a lo largo de los años, la alta disponibilidad de estos hace que su uso para intento de autolisis siga presentándose. Su presentación clínica es variada y dado el riesgo de mortalidad asociada, es importante que esta patología sea rápidamente reconocida por los médicos que los reciben para iniciar un manejo oportuno y eficaz. Objetivo: presentar el enfrentamiento inicial y manejo terapéutico de la intoxicación por ATC desde la perspectiva de la medicina de urgencia. Método: se realizó una revisión bibliográfica de la literatura científica sobre el manejo de un paciente intoxicado por ATC. Se presenta la evidencia actual de las intervenciones terapéuticas más utilizadas. respecto al manejo inicial y enfrentamiento de la intoxicación por antidepresivos tricíclicos, en el contexto de la atención en un servicio de urgencia. Conclusión: la intoxicación por ATC puede presentarse con síntomas leves y signos precoces, así como con síntomas graves e incluso fatales, dados principalmente por complicaciones cardiovasculres y neurológicas. Su manejo se basa en el reconocimiento precoz, medidas de soporte y terapias específicas según la clínica que presente.

Managing poisoned patients continues to be a challenge for health personnel. Tricyclic antidepressant are a frequent diagnosis, and a pathology their can be very serious. Although the therapeutic indications for these drugs have changed over the years, their high availability means that their use for suicidal attempts continues to be present. Its clinical presentation is varied and given the mortality risk, it is crucial that this entity must be rapidly recognized by the physicians who care for them to initiate timely and effective treatment. Objective: Present the initial management and therapeutic strategies for tricyclic antidepressant intoxication, from emergency medicine perspective. Method: Bibliographic review of the scientific literature on this subject. Current evidence of the most widely used therapeutic interventions is described regarding the initial management and disposition of tricyclic antidepressant intoxication in the emergency department.

Evaluation of the Anticonvulsant and Antidepressant Effects of the Aqueous Extract of the Leaves of Ascotheca paucinervia (T. Anderson ex C.B. Clarke) Heine in Mice

The present study was undertaken to evaluate the anticonvulsant and antidepressant effects of Ascotheca paucinervia leaves on mice by using strychnine at 2.5mg/kg to induce convulsions and the forced swimming test to create a stressful situation, respectively. Concerning convulsions, only the 500mg/kg extract significantly increases (p<0.001) the time to onset of convulsions and it non-significantly reduces the duration of convulsions induced by strychnine. In addition, the extract reduces very significantly in a dose-dependent manner the time of immobility and it significantly increases the swimming time as well as the climbing time at both doses. At the same time, the estimation of the acute toxicity of the extract from the leaves of Ascotheca paucinervia according to guideline No. 425 of the OECD (2022) shows that the latter is weakly toxic and its LD50 is greater than 5000mg/kg. In addition, the evaluation of the sedative effect of this extract shows that it produces a dose-dependent sedative effects and at doses of 250m/kg and 500mg/kg, the extract significantly potentiates the sleep induced by phenobarbital. In summary, the results obtained suggest that Ascotheca paucineervia leaves extract possesses anticonvulsant and antidepressant effects.

Effect of antidepressants on thyroid hormone level in adolescent depression with suicidal ideation / 上海预防医学

ObjectiveTo compare the differences in thyroid hormone levels between adolescents with and without suicidal ideation， and to explore the association between thyroid hormone/suicidal ideation and the antidepressant treatment. MethodsA total of 100 patients were divided into non-suicidal ideation group and suicidal ideation group according to the SIOSS. The levels of thyroid-stimulating hormone （TSH）， triiodothyronine （T3）， thyroxine （T4）， free triiodothyronine （FT3） and free thyroxine （FT4） were compared between the two groups as well as their changes after 6 weeks of antidepressant treatment. ResultsThe levels of FT3， FT4 and T4 in the non-suicidal ideation group were higher than those in the suicidal ideation group. After 6 weeks of antidepressant treatment， the levels of FT3， FT4 and T4 in the suicide ideation group were higher than those before the treatment. The FT3 level in the male non-suicidal ideation group was higher than that in the suicidal ideation group. The levels of FT4 and T4 in the female non-suicidal ideation group were higher than those in the suicidal ideation group （all P<0.05） ConclusionThere are differences in thyroid hormone levels between adolescents with and without suicidal ideation （both with first-episode depression）， and patients with suicidal ideation have significant changes after treatment with antidepressants.

A novel NMDA receptor modulator:antidepressant ef-fect and mechanism of GW043 / 中国药理学与毒理学杂志

OBJECTIVE The N-methyl-D-aspartate(NMDA)receptor has been shown to be strongly associ-ated with rapid antidepressant effects.GW043 is a com-pound with a novel structure that we designed and syn-thesized to act on the NMDA receptor(NMDAR).METH-ODS In this study,we first confirmed the target of GW043 using a receptor binding assay.We observed the effect of GW043 on NMDAR currents in vivo and in vitro assays using a membrane clamp technique with a view to characterizing the function of GW043.We investi-gated the antidepressant effect of GW043 in rodent behavioral models such as FST,TST and CUMS.Fur-thermore,we explored the mechanism of GW043 onset using Western blotting,BrdU staining,Golgi staining and electrophysiological techniques.RESULTS GW043 interacts with high affinity only at the NMDAR.Electro-physiological studies have indicated that GW043 is a par-tial agonist of NMDAR.Meanwhile,behavioral experi-ments were conducted to confirm the antidepressant effect of GW043 in rodents.The mechanism study found that GW043 regulate synaptic plasticity through LTP and BDNF/mTOR pathways and increase the number of new-born neurons to cause antidepressant effects.GW043,a partial agonist of NMDAR,reversed depression-like behav-ior in rats by modulating synaptic plasticity,suggesting an antidepressant effect.CONCLUSION The results suggest that GW043 is a partial agonist of NMDA recep-tors and has significant antidepressant effects.

A Comprehensive Overview of the Role of Visual Cortex Malfunction in Depressive Disorders: Opportunities and Challenges / 神经科学通报·英文版

Major depressive disorder (MDD) is a highly heterogeneous mental disorder, and its complex etiology and unclear mechanism are great obstacles to the diagnosis and treatment of the disease. Studies have shown that abnormal functions of the visual cortex have been reported in MDD patients, and the actions of several antidepressants coincide with improvements in the structure and synaptic functions of the visual cortex. In this review, we critically evaluate current evidence showing the involvement of the malfunctioning visual cortex in the pathophysiology and therapeutic process of depression. In addition, we discuss the molecular mechanisms of visual cortex dysfunction that may underlie the pathogenesis of MDD. Although the precise roles of visual cortex abnormalities in MDD remain uncertain, this undervalued brain region may become a novel area for the treatment of depressed patients.

Identification of the antidepressant fraction and its major chemical constituents of Radix Paeoniae Alba / 药学学报

The goal of this work was to investigate the antidepressant fraction from Radix Paeoniae Alba and identify its major chemical constituents. Corticosterone injured rat phaeochromocytoma (PC12) cells and behavioral despair depression models of mice were used to evaluate the antidepressant effects of Radix Paeoniae Alba (Bai-Shao) ethanol extract (BS-E) and its three fractions (BS-10E, BS-60E, BS-95E) isolated by macroporous resin column chromatography. Animal experimental procedures were approved by the Animal Ethics Committee of the Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College (approval No.: SLXD-20210618051). The results showed that BS-E, BS-10E and BS-60E had protective effects against PC12 cells injury induced by corticosterone, among which BS-60E had the strongest protective effect. BS-60E could significantly shorten the time of forced swimming and tail suspension in despair depression models of mice, and was identified as the antidepressant fraction of Radix Paeoniae Alba. The major chemical constituents in the antidepressant fraction were identified by ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS), and their proposed fragmentation pathways in MS spectra were deduced. A total of 79 chemical constituents were identified from BS-60E, including 36 monoterpenes, 34 polyphenols, 6 oligosaccharides, and 3 other constituents, and monoterpenes and polyphenols may be major effective constituents of BS-60E.

Expert consensus on comprehensive clinical evaluation of antidepressant drugs / 中国药房

At present， many antidepressant drug categories have been marketed in China， but still lack a scientific and standardized system for drug comprehensive clinical evaluation. To guide and promote medical institutions to standardize the comprehensive clinical evaluation of antidepressant drugs， 19 clinical， pharmacy and evidence-based medicine experts from China were organized by the China Population Welfare Foundation to evaluate 11 drugs in 5 categories， including sertraline/escitalopram/ paroxetine/fluvoxamine/citalopram/fluoxetine/venlafaxine/duloxetine/vortioxetine/agomelatine/mirtazapine， through seminars and interviews， concerning clinical real-world data and evidence-based medicine， and to form the first draft of Expert Consensus on Comprehensive Clinical Evaluation of Antidepressant drugs， which is finalized after peer review by 18 clinical and pharmacy experts. The evaluation system of this expert consensus adopts the quantitative evaluation system of percentile and carries out a systematic evaluation from 6 dimensions of effectiveness， safety， economy， suitability， accessibility and innovativeness， while the evaluation dimensions are more detailed， with the operability of the drug evaluation system and the characteristics of drugs in the field of antidepressants. It aims to provide a theoretical basis for the rational use of drugs in the field of psychiatric disorders in medical institutions and help improve the quality of pharmacy services to better meet the needs of the people for medication.

A Comprehensive Overview of the Role of Visual Cortex Malfunction in Depressive Disorders: Opportunities and Challenges / 神经科学通报·英文版

Major depressive disorder (MDD) is a highly heterogeneous mental disorder, and its complex etiology and unclear mechanism are great obstacles to the diagnosis and treatment of the disease. Studies have shown that abnormal functions of the visual cortex have been reported in MDD patients, and the actions of several antidepressants coincide with improvements in the structure and synaptic functions of the visual cortex. In this review, we critically evaluate current evidence showing the involvement of the malfunctioning visual cortex in the pathophysiology and therapeutic process of depression. In addition, we discuss the molecular mechanisms of visual cortex dysfunction that may underlie the pathogenesis of MDD. Although the precise roles of visual cortex abnormalities in MDD remain uncertain, this undervalued brain region may become a novel area for the treatment of depressed patients.

Anxiolytic and antidepressant effects of agarwood inhalation and its mechanism / 中国中药杂志

This study used m-chloropheniperazine(MCPP) and chronic unforeseeable mild stress(CUMS) to induce the rat models of anxiety and depression, respectively. The behaviors of rats were observed by the open field test(OFT), light-dark exploration test(LDE), tail suspension test(TST), and forced swimming test(FST), and the antidepressant and anxiolytic effects of agarwood essential oil(AEO), agarwood fragrant powder(AFP), and agarwood line incense(ALI) were explored. The enzyme-linked immunosorbent assay(ELISA) was used to determine the levels of 5-hydroxytryptamine(5-HT), glutamic acid(Glu), and γ-aminobutyric acid(GABA_A) in the hippocampal area. The Western blot assay was used to determine the protein expression levels of glutamate receptor 1(GluR1) and vesicular glutamate transporter type 1(VGluT1), exploring the anxiolytic and antidepressant mechanism of agarwood inhalation. The results showed that compared with the anxiety model group, the AEO, AFP, and ALI groups decreased the total distance(P<0.05), decreased the velocity of movements(P<0.05), prolonged the immobile time(P<0.05), and reduced the distance and velocity of the rat model of anxiety in the dark box(P<0.05). Compared with the depression model group, the AEO, AFP, and ALI groups increased the total distance and average velocity(P<0.05), reduced the immobile time(P<0.05), and reduced the forced swimming and tail suspension time(P<0.05). In terms of transmitter regulation, the AEO, AFP, and ALI groups decreased the level of Glu in the rat model of anxiety(P<0.05) and increased the levels of GABA_A and 5-HT(P<0.05), while the AEO, AFP, and ALI groups all increased the level of 5-HT in the rat model of depression(P<0.05) and decreased the levels of GABA_A and Glu(P<0.05). At the same time, the AEO, AFP, and ALI groups all increased the protein expression levels of GluR1 and VGluT1 in the hippocampus of the rat models of anxiety and depression(P<0.05). In conclusion, AEO, AFP, and ALI exert anxiolytic and antidepressant effects, and the mechanism might be related to the regulation of the neurotransmitter and the protein expression of GluR1 and VGluT1 in the hippocampus.

Improvement of cognitive function by escitalopram and paroxetine in patients with first-episode depressive disorder and its relationship with thyroid hormone levels / 四川精神卫生

BackgroundThe incidence of cognitive impairment in patients with depressive disorder is high， and the causes and mechanisms of which deserve more attention. It is usual that the thyroid hormone levels in patients with depressive disorder alter. Further research is needed to explore whether the cognitive function changes in patients with depressive disorder are related to thyroid hormone levels. ObjectiveTo explore the improvement of cognitive function in patients with first-episode depressive disorder after escitalopram and paroxetine treatment， and to analyse its correlation with thyroid hormone levels， so as to look for potential biomarkers of cognitive function change in patients with depressive disorder. MethodsFrom March 2021 to March 2022， 120 patients who met the diagnostic criteria of the International Classification of Diseases， tenth edition （ICD-10） for depression and were hospitalized at Shandong Mental Health Center were selected as the research objects. They were randomly divided into two groups by random number table method with 60 patients in each group. The two groups were treated with escitalopram （starting dose 5 mg/d） and paroxetine （starting dose 20 mg/d） for 6 weeks. Before and 6 weeks after the treatment， levels of thyroid stimulating hormone （TSH）， free thyroxine （FT4） and free triiodothyronine （FT3） were tested respectively. Depression degree and cognitive function level were assessed using the Hamilton Depression Scale-17 item （HAMD-17） and Montreal Cognitive Assessment （MoCA）， respectively. Pearson or Spearman correlation analysis was used to examine the correlation between the MoCA score difference before and after the treatment and the post-treatment level of thyroid hormone. ResultsBefore and 6 weeks after the treatment， the time effect of HAMD-17 total score in both groups was statistically significant （F=1 236.568， P<0.01）. Also， the time effect， group effect as well as interaction effect of time and group of MoCA total score in both groups were statistically significant （F=79.186， 6.026， 20.417， P<0.05 or 0.01）. The time effect， group effect as well as the interaction effect of time and group for FT3 level and FT4 level were statistically significant in both groups （F=75.973， 20.287， 0.961， 84.194， 0.142， 8.299， P<0.05 or 0.01）. According to the simple effect analysis. After the treatment， the MoCA total score in both groups was higher than that before treatment， while FT3 and FT4 levels were lower than those before treatment （F=15.864， 5.421， 8.524， 6.443， 7.628， 3.639， P<0.01）. After the 6-week treatment， the MoCA total score as well as FT3 and FT4 level differences in escitalopram and paroxetine groups were of statistical significance （t=5.841， -0.705， -2.349， P<0.05 or 0.01）. The MoCA score difference before and after treatment in paroxetine group was positively correlated with FT3 and FT4 levels after treatment （r=0.276， 0.382， P<0.05 or 0.01）. ConclusionBoth escitalopram and paroxetine can improve cognitive function in patients with first-episode depressive disorder. The improvement may be related to the changes in serum FT3 and FT4 levels.

Gender differences in antidepressant effect of raw Rehmanniae Radix / 中国中药杂志

For the first time, this study evaluated the gender differences and mechanisms of the antidepressant effects of raw Rehmanniae Radix(RRR) based on the classic depression model with traditional Chinese medicine syndrome of Yin deficiency and internal heat. The depression model with Yin deficiency and internal heat was established by the widely recognized and applied method of thyroxine induction of the classic depression model with Yin deficiency and internal heat(chronic unpredictable mild stress). Male and female mice were simultaneously treated with RRR. The study analyzed indicators of nourishing Yin and clearing heat, conventional antidepressant efficacy test indicators, and important biomolecules reflecting the pathogenesis and prevention and treatment mechanisms of depression, and conducted a correlation analysis of antidepressant efficacy, Yin-nourishing and heat-clearing efficacy, and biological mechanism in different genders, thereby comprehensively assessing the antidepressant effects of RRR on depression of Yin deficiency and internal heat, as well as its gender differences and mechanisms. RRR exhibited antidepressant effects in both male and female mouse models, and its antidepressant efficacy showed gender differences, with a superior effect observed in females. Moreover, the effects of RRR on enhancing or improving hippocampal neuronal pathology, nucleus-positive areas, postsynaptic dense area protein 95, and synaptophysin protein expression were more significant in females than in males. In addition, RRR significantly reversed the abnormal upregulation of nuclear factor(NF)-κB/cyclooxygenase 2(COX2)/NOD-like receptor thermal protein domain associated protein 3(NLRP3) pathway proteins in the hippocampus of both male and female mouse models. The antidepressant effects of RRR were more pronounced in depression female mice with Yin deficiency and internal heat syndrome, possibly due to the improvement of neuronal damage and enhancement of neuroplasticity. The antidepressant mechanisms of RRR for depression with Yin deficiency and internal heat syndrome may be associated with the downregulation of the NF-κB/COX2/NLRP3 pathway to reduce neuronal damage and enhance neuroplasticity.

Adverse Psychological and Therapeutic Effects of Kratom (Mitragyna speciosa) Use: A Systematic Review

@#Aims: This review aimed to comprehensively examine kratom’s therapeutic potential for treatment of mental health-related issues as well as any related benefits and risks. Design: Systematic review. Data sources: Google Scholar, Web of Science, PubMed, Scopus, PsycINFO, EMBASE, Cochrane Library, and Medline. Review methods: Three authors carried out electronic search of articles published between 1950 to September 2022 through major databases for a duration of three months (from July to September 2022). Each author independently screened the literature for inclusion and exclusion criteria, the findings were then compared, discrepancies between authors were resolved, and the final selection of articles were reviewed. Results: A total of 46 articles were included in this review. A total of three in vitro and animal studies and five cross-sectional online surveys reported the therapeutic potential of kratom in opioid replacement therapy. In addition, a total of two animal studies and three cross-sectional online surveys highlighted the role of kratom as a potential antidepressant and anxiolytic. Contrastingly, two animal studies, 11 studies in human subjects, and 16 case reports documented the risk of kratom dependence, cravings, tolerance, and kratom-related substance use disorder as the major safety concern of implementing kratom use as a therapeutic agent. Conclusion and impact: In the absence of human clinical trial, coupled with various considerable adverse events of kratom (not limited to psychological side effects), evidence to support kratom as potential therapeutic use remains inconclusive.