The Antidepressant-Like Effects of <i>Punica granatum</i>(Pomegranate) Extract in Mice

The aim of the present work is to evaluate the putative antidepressant-like effects of pomegranate fruit extract including seeds (PFE) on the performance of male mice in the forced swimming test (FST), after acute administration, after short-term treatment (7 days) and, after repeated administration in a 24-h period (24, 12 and 1 h before swimming test). A single dose (20 ml/kg p.o.) of PFE, in male mice provoked a significant reduction of the immobility time. Such effect was also observed with short-term treatment (7 days) with doses of 1 and 10 ml/kg/day of PFE. Moreover, it was noted that there were important differences in the onset of the antidepressant-like effect in the FST, depending on the modality of treatment with PFE. Both efficacy and potency were higher when repeated administration of PFE was used, and surprisingly the dose of 10 ml/kg (24, 12 and 1 h before swimming test) was as effective as Fluoxetine. In the same way, the short term administration (7 days) improved significantly efficacy and potency of the PFE in comparison to a single dose treatment. These results indicate an antidepressant-like profile of action for PFE which deserves further research.

Antidepressant Effects of Ginsenosides from Panax notoginseng

Ginsenosides Rg 1,Rb 1,R 1,Rd,and Re are major constituents of Panax notoginseng,a famous traditional Chinese medicinal herb,which has both stimulative and inhibitory effects on the central nervous system (CNS).The monoamine hypothesis proposes that depression is a result of the depletion of 5-hydroxytryptamine (5-HT),norepinephrine (NE) and dopamine (DA) in addition to the activation of monoamine oxidase in the CNS.The purpose of this study was to determine whether P.notoginseng Saponin (PNS) has an antidepressant activity.We investigated the antidepressant-like activities of Rg 1,Rb 1,R 1,Rd,and Re in mice,using two animal models of depression.In addition,we analyzed the neurochemicals by the chronic unpredictable mild stress test.Our results showed that Rb 1,Rd,and Re treatment at 10 mg kg-1 significantly reduced the duration of immobility in both the tail suspension and forced swimming tests.Rb 1,Rd,and Re increases in 5HT and NE levels at 10 mg kg-1 in both the frontal cortex and hippocampus.Dopamine levels increased in the hippocampus and the striatum.Moreover,5-hydroxyindoleacetic acid (5-HIAA) levels were found increased in the hippocampus.These findings suggest that the antidepressant effects of Rb 1,Rd,and Re may be related to the increase in 5-HT and NE in the CNS,and through the alterations in the synthesis or metabolism of dopamine.

Novel antidepressants targeting TREK1 channel

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.

Misunderstanding of a New Approach to Drug-Placebo Difference Calculation in Short Term Antidepressant-Drug Trials

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.

Single Exposure to Antidepressants during Infancy Is Associated with Delayed Behavioral Changes in C57BL/6 Mice

As serotoninergic transmission plays a crucial role in higher brain function in mammals, the disturbance of this system will likely have significant effects on emotion and cognition. Previous studies have reported that chronic treatment with Specific Serotonin Reuptake Inhibitors (SSRIs) during both late pregnancy and lactation was associated with abnormal behavior in adult rats. These data imply that disturbances in serotoninergic transmission during neurodevelopment may have negative effects on both the structure and function of the resultant adult brain. Therefore, the effect of a single exposure to an SSRI or a tricyclic antidepressant that preferentially inhibits serotonin reuptake during the pre-weaning period was examined in adult mice. An oral infusion of paroxetine (70 mg/kg), fluvoxamine (250 mg/kg), clomipramine (180 mg/kg), or saline was administered on postnatal day 14. Starting at 11 weeks of age, mice were assessed using a comprehensive behavioral test battery. Mice treated with paroxetine demonstrated altered behavior on the open field and hole-board tasks;those treated with fluvoxamine had behavioral changes on the light-dark box, hole-board, and sucrose preference tasks, while alteration in forced swimming and cued fear behavior were noted in mice treated with clomipramine. These results suggest that even a single administration of an antidepressant could have profound effects on behavior in adulthood, although the effects might differ dependent on the specific drug that was administered.

Pharmacological Effects and Molecular Mechanism of Synephrine Hydrochloride

Synephrine hydrochloride,an alkaloid compound extracted from immature bitter orange,has many pharmacological effects such as anticancer effect,antioxidant effect and antidepression effect.In this paper,the pharmacological effects and mechanism of synephrine hydrochloride were reviewed in order to provide a theoretical basis for the development and application of synephrine hydrochloride.

酸枣仁皂苷A对抑郁小鼠行为及突触可塑性相关蛋白的作用

该文探究了酸枣仁皂苷A(Jujuboside A,JuA)对抑郁模型小鼠行为及神经突触可塑性相关蛋白表达的作用。通过悬尾实验、强迫游泳实验、旷场实验、Morris水迷宫实验评价小鼠的抑郁状态,免疫组织化学染色法检测小鼠海马组织中脑源性神经营养因子(Brain Derived Neurotrophic Factor,BDNF)的表达水平,Western blot实验检测小鼠海马组织酪氨酸激酶受体B(Tyrosine Kinase Receptor B,TrkB)、cAMP反应元件结合蛋白(cAMP Responsive Element Binding,CREB)、突触后密度蛋白95(Postsynaptic Density Protein 95,PSD95)、自噬效应蛋白Beclin1(Autophagy Effector Protein Beclin1,Beclin1)的表达水平。结果表明,JuA显著改善抑郁模型小鼠的抑郁状态。同时,JuA作用后海马组织BDNF、TrkB、CREB、PSD95、Beclin1的表达水平较模型组分别上调了190.23%、137.24%、76.29%、169.32%、82.53%。综上所述,JuA对抑郁模型小鼠具有显著的抗抑郁作用,并能明上调BDNF、TrkB、CREB、PSD95、Beclin1等神经突触可塑性相关蛋白的表达。实验结果为JuA在抑郁症临床治疗方面的应用提供理论依据,并为探究抑郁症药物治疗靶点提供参考。

青少年抑郁症使用抗抑郁药物的临床进展

青少年抑郁症患者相较于成年抑郁症患者,具有更高的发病率、较差的生活质量和治疗效果。国际指南普遍推荐轻度青少年抑郁症优先考虑心理治疗,对于中重度患者,抗抑郁药物联合心理治疗是1种可行的选择,如何选择适合的抗抑郁药物仍然是待解决的难题。抗抑郁药物存在一系列副作用,包括睡眠障碍、锥体外系反应和消化道反应等,为了减轻这些副作用并提高临床疗效,个体化的治疗方案至关重要。总结了青少年抑郁症的发病机制、抗抑郁药物的药代动力学和副作用,以及2013~2023年针对青少年抑郁症患者的用药指南,并针对青少年抑郁症患者药物治疗方案提出科学建议。

钾离子通道在抑郁症治疗中的研究进展

抑郁症是一种由多种因素引起的情感障碍性疾病,其发病率呈现逐年上升趋势,严重危害人类的身心健康。当前抗抑郁药的治疗机制主要是以增加脑内5-羟色胺、去甲肾上腺素和多巴胺等单胺递质的浓度为主,但其存在抗抑郁响应率低、不良反应严重等缺点。因此,抑郁症治疗仍未满足临床需求。近年来越来越多的临床前研究和临床实验表明,钾离子通道开放剂或拮抗剂在抑郁症治疗中具有巨大潜力。该文重点综述了近年来钾离子通道中电压门控钾离子通道、双孔钾离子通道与抑郁症的相关研究进展,为新型抗抑郁药物的研发提供新的思路。

Combination of Geniposide and Eleutheroside B Exerts Antidepressant-like Effect on Lipopolysaccharide-Induced Depression Mice Model

Objective To study the antidepressant-like effect and action mechanism of geniposide and eleutheroside B combination treatment on the lipopolysaccharide(LPS)-induced depression mice model.Methods Depression mice model was established by lipopolysaccharide(LPS)injection.Totally 48 mice were randomly divided into 6 groups(8 rats per group)according to a random number table,including normal,model,fluoxetine(20 mg/kg),geniposide(100 mg/kg)+eleutheroside B(100 mg/kg),geniposide+eleutheroside B+WAY 100635(0.03 mg/kg),geniposide+eleutheroside B+N-methyl-D-aspartic acid receptor(NMDA,75 mg/kg)groups,respectively.After continuous administration for 10 days,autonomic activity tests after 30 min of administration were performed on the 10th day.On the 11th day,except for the normal group,the mice in the other groups were intraperitoneally injected with LPS(1 mg/kg),and the behavioral tests were performed 4 h later.Enzyme linked immunosorbent assay was used to detect tumor necrosis factor alpha(TNF-α)and interleukin-1β(IL-1β)levels in mice serum.The mRNA expression of indoleamine 2,3-dioxygenase(IDO)and nuclear transcription factor(NF-κB)were detected by real-time quantitative polymerase chain reaction.Western-blot analysis was used to detect IDO and NF-κB protein expressions in hippocampus tissue.Results Compared with the normal group,a single administration of LPS increased the immobility time in the forced swimming test(FST)and tail suspension test(TST,P<0.01),without affecting autonomous activity.Compared with the model group,fluoxetine and geniposide+eleutheroside B administration significantly improved the immobility time of depressed mice in the FST and TST,decreased serum IL-1βcontent,inhibited the expression levels of NF-κB gene and protein in hippocampus tissues(P<0.05 or P<0.01).Compared with the model group,geniposide+eleutheroside B treatment significantly reduced serum TNF-αcontent and inhibited IDO mRNA and protein expressions in hippocampus(P<0.05 or P<0.01).In addition,NMDA partly prevented the inhibition of IDO mRNA expression by geniposide+eleutheroside B;NMDA and WAY-100635 also partly prevented the reduction of IL-1ßcontent induced by geniposide+eleutheroside B treatment(P<0.05 or P<0.01).Conclusions The combination of geniposide and eleutheroside B showed a certain antidepression-like effect.Its main mechanism of action may be contributed to inhibiting the activation of NF-κB,decreasing the proinflammatory cytokines such as TNF-α,IL-1β,and inhibiting in the neuroinflammatory reaction.Additionally,it also affects tryptophan metabolism,reduces the expression of a key enzyme of tryptophan metabolism,IDO.And this antidepressant-like effect may be mediated by 5-hydroxytryptamine and glutamate systems.

Coherent effect of triple-resonant optical parametric amplification inside a cavity with injection of a squeezed vacuum field

In theory, we study the quantum tluctuatlons ot tlae suDllarmonlc renecteu nela Irom a ulplc-rc^ulltUtt IdU^ClIClatC optical parametric amplifier （OPA） inside an optical cavity. We discuss two cases, where the linewidth of the harmonic field is either much narrower or broader than the subharmonic field. Since an electromagnetically-induced-transparency （EIT）-like effect can be simulated in a triple-resonant OPA, the output spectra from a triple-resonant OPA with a squeezed vacuum input may simulate the phenomenon of the response of an EIT medium for squeezed states. This scheme can be implemented with present experimental setups.

Design of 8-like Non-planar Cavity

For eliminating the negative effects of lock-in region and optical elements in cavity,the non-planar structure is strongly needed in laser gyro. In this paper,the theoretical formula of rotatory effect in non-planar cavity is presented deducing from basic light propagating law. Based on the 8-like plane cavity,a novel non-planar structure is designed and numerically calculated. The results show that for obtaining the required rotatory angle,it just needs to adjust the structural parameters of the original 8-like plane cavity. The four-frequency-differential laser gyro which adopts the non-planar 8-like structure has the same advantages as those with the planar 8-like structure,such as the gain region locates at one leg,the position of Faraday rotator has better spatial symmetry and the coating films of the output mirror is easily designed.

油莎草须根油树脂成分及抗抑郁作用分析

揭示油莎草须根油树脂抗抑郁作用及成分。采用超高效液相色谱与串联四级杆飞行时间质谱联用技术分析油莎草须根油树脂化学成分;建立慢性不可预见温和应激(chronic unpredictable mild stress,CUMS)抑郁小鼠模型,从动物行为学、神经递质含量变化、海马组织病理学考察油莎草须根油树脂抗抑郁作用。结果表明:油莎草须根油树脂含有酮类(68.891%)、酯类(8.787%)、醇类(4.258%)、烯类(0.374%)及其他物质(12.879%),主要成分为α-香附酮(59.536%)、吉马酮(5.875%)。CUMS抑郁模型小鼠给药后,油莎草须根油树脂显著缩短了小鼠强迫游泳静止时间,悬尾静止时间;显著提高了中央总路程、平均速度、中央持续时间,油莎草须根油树脂高剂量组明显提升了小鼠血清中5-羟色胺(5-HT)含量、去甲肾上腺素(NE)含量,油莎草须根油树脂高剂量组小鼠海马细胞排列整齐,神经元细胞膜基本完整。油莎草须根油树脂可能通过参与调节CUMS抑郁模型小鼠血清中5-HT和NE的表达,修复小鼠海马组织损伤来改善抑郁样行为。

抗抑郁药物对生殖功能影响的研究进展

随着社会压力增大,青中年人群抑郁症患病率日益增高。《2022国民抑郁症蓝皮书》显示,19~40岁的抑郁症患者比例为65.14%,处于育龄期内的人群长期使用抗抑郁药物是否会对其生殖功能造成影响尚无明确结论。本文列举了目前临床常用的抗抑郁药物[包括三环/四环类抗抑郁药物、选择性五羟色胺(5-HT)再摄取抑制剂、5-HT与去甲肾上腺素(NE)再摄取抑制剂、褪黑素类及中药制剂等],系统总结了不同类型药物对生殖功能的影响,以期为育龄期抑郁症患者的用药选择提供一定参考。

淡豆豉化学成分及抗抑郁作用研究进展

淡豆豉是以豆科植物大豆的干燥成熟种子(黑豆)为原料,经微生物发酵得到的中国传统发酵类药物,味苦、辛,性凉,归肺、胃经;有解表、除烦躁、疏泄郁结之功效。越来越多研究表明淡豆豉对抑郁症有明显的疗效,且与其所含化学成分有关。因此,本文对淡豆豉所含化学成分现状及抗抑郁作用研究进展进行系统总结和分析,并明确淡豆豉抗抑郁作用与成分的关系,为今后淡豆豉抗抑郁产品开发利用提供依据和参考。

心理疗法联合抗抑郁药物治疗心脏神经官能症的效果分析

目的探究心理疗法联合抗抑郁药物治疗心脏神经官能症的临床效果。方法150例心脏神经官能症患者,采用随机数字表法分为参比组和实验组,每组75例。参比组患者给予常规抗抑郁药物治疗,实验组患者在参比组基础上配合心理疗法治疗。比较两组患者治疗前后的抑郁、焦虑、心脏症状评分及治疗效果、治疗满意度。结果治疗后,实验组患者的抑郁、焦虑及心脏症状评分分别为(48.82±4.98)、(43.14±3.28)、(42.11±2.32)分,明显低于参比组的(56.71±5.12)、(51.68±4.56)、(53.12±3.12)分,差异具有统计学意义(P<0.05)。治疗后,实验组患者的与人相处、日常生活、生理状态及心理状态评分分别为(68.28±5.28)、(69.21±5.42)、(70.12±3.22)、(60.52±5.52)分,明显高于参比组的(59.61±4.56)、(59.88±4.29)、(60.02±2.34)、(51.11±4.36)分,差异具有统计学意义(P<0.05)。实验组患者的治疗总有效率96.00%明显高于参比组的82.67%,差异具有统计学意义(P<0.05)。实验组患者的治疗满意度93.33%明显高于参比组的80.00%,差异具有统计学意义(P<0.05)。结论在临床中对心脏神经官能症患者同时应用心理疗法和抗抑郁药物治疗,可有效减轻其抑郁和焦虑程度,并提升患者的治疗总有效率、生活质量及满意程度,可广泛应用在临床中。

Can acupuncture enhance therapeutic effectiveness of antidepressants and reduce adverse drug reactions in patients with depression? A systematic review and meta-analysis

Background: Some depressed patients receive acupuncture as an adjunct to their conventional medications.Objective: This review aims to provide evidence on whether acupuncture can enhance the therapeutic effectiveness of antidepressants for treating depression, and explore whether acupuncture can reduce the adverse reactions associated with antidepressants.Search strategy: English and Chinese databases were searched for randomized controlled trials(RCTs)published until December 1, 2021.Inclusion criteria: RCTs with a modified Jadad scale score ≥ 4 were included if they compared a group of participants with depression that received acupuncture combined with antidepressants with a control group that received antidepressants alone.Data extraction and analysis: Meta-analysis was performed, and statistical heterogeneity was assessed based on Cochran’s Q statistic and its related P-value. Primary outcomes were the reduction in the severity of depression and adverse reactions associated with antidepressants, while secondary outcomes included remission rate, treatment response, social functioning, and change in antidepressant dose.The Grading of Recommendations Assessment, Development and Evaluation(GRADE) framework was used to evaluate the overall quality of evidence in the included studies.Results: This review included 16 studies(with a total of 1958 participants). Most studies were at high risk of performance bias and at low or unclear risk of selection bias, detection bias, attrition bias, reporting bias, and other bias. Analysis of the 16 RCTs showed that, compared with antidepressants alone, acupuncture along with antidepressants reduced the Hamilton Depression Rating Scale-17(HAMD-17) scores(standard mean difference [SMD]-0.44, 95% confidence interval [CI]-0.55 to-0.33, P < 0.01;I^(2)= 14%), Self-rating Depression Scale(SDS) scores(SMD-0.53, 95% CI-0.84 to-0.23, P < 0.01;I^(2)= 79%), and the Side Effect Rating Scale(SERS) scores(SMD-1.11, 95% CI-1.56 to-0.66, P < 0.01;I^(2)= 89%). Compared with antidepressants alone, acupuncture along with antidepressants improved World Health Organization Quality of Life-BREF scores(SMD 0.31, 95% CI 0.18 to 0.44, P < 0.01;I^(2)= 15%), decreased the number of participants who increased their antidepressant dosages(relative risk[RR] 0.32, 95% CI 0.22 to 0.48, P < 0.01;I^(2)= 0%), and resulted in significantly higher remission rates(RR1.52, 95% CI 1.26 to 1.83, P < 0.01;I^(2)= 0%) and treatment responses(RR 1.35, 95% CI 1.24 to 1.47, P < 0.01;I^(2)= 19%) in terms of HAMD-17 scores. The HAMD-17, SDS and SERS scores were assessed as low quality by GRADE and the other indices as being of moderate quality.Conclusion: Acupuncture as an adjunct to antidepressants may enhance the therapeutic effectiveness and reduce the adverse drug reactions in patients receiving antidepressants. These findings must be interpreted with caution, as the evidence was of low or moderate quality and there was a lack of comparative data with a placebo control.Systematic review registration: INPLASY202150008.

基于QuEChERS净化-高效液相色谱-串联质谱法测定水产品中8种抗抑郁类药物残留量

抗抑郁类药物的污染可导致水产品中残留量超标,从而对食品卫生安全构成威胁。采用QuEChERS净化-高效液相色谱-串联质谱法测定,以鱼、虾、蟹、贝等常见水产品作为样品基质,建立西酞普兰、文拉法辛、帕罗西汀、氟西汀、阿米替林、曲米帕明、舍曲林、氯丙咪嗪8种抗抑郁类药物残留量的检测方法。结果表明:8种抗抑郁类药物在0.1~5.0μg/L质量浓度范围内线性良好,相关系数均大于0.999,检出限为0.04~0.06μg/kg,加标回收率为80.0%~110.0%,相对标准偏差为0.23%~5.50%。该方法简单快速、干扰小、线性范围良好,同时具有较好的精密度和准确度。

中医定向透药治疗联合抗抑郁药对抑郁症患者的疗效和安全性观察

目的 研究分析中医定向透药治疗联合抗抑郁药对抑郁症患者的临床疗效及安全性。方法 选取2020年1月-2021年6月在苏州市广济医院治疗的100例抑郁症患者为研究对象,根据患者治疗方式不同分成对照组和观察组,每组50例。其中,对照组单纯应用抗抑郁药治疗,观察组联合应用抗抑郁药与中医定向透药治疗,持续治疗4周,对两组患者临床疗效、心理状态、应对方式、治疗安全性采用t检验,并进行统计比较。结果观察组明显高于对照组(P<0.05)。治疗前两组汉密尔顿焦虑量表(hamilton anxiety scale,HAMA)、汉密尔顿抑郁量表(hamilton depression scale,HAMD)分值差异比较不明显(P>0.05);治疗2周后、4周后,观察组在HAMA、HAMD分值方面均显著低于对照组(P<0.05)。两组治疗前SCSQ调查评分结果比较差异无统计学意义(P>0.05);经治疗2周后、4周后,观察组积极应对得分显著高于对照组,消极应对评分明显低于对照组(P<0.05)。对于安全性来说,两组对比差异无统计学意义(P>0.05)。结论 抑郁症患者应用抗抑郁药联合中医定向透药治疗的效果更好,不仅可以调节患者心理状态,还可以改善患者应对方式,且不会明显增加不良反应的发生概率,具有安全、可靠的特点,值得临床深入研究与推荐应用。

巴戟天寡糖对获得性无助抑郁模型大鼠行为的影响

目的建立大鼠获得性无助模型口服给药途径评价药物抗抑郁作用的方法,并观察口服巴戟天寡糖在该模型上的抗抑郁效应.方法采用微机程序控制的大鼠穿梭箱反应仪,给予不可逃避的足底电击建立获得性无助模型,进行条件性回避反应训练,测定大鼠的逃避失败次数. 结果模型对照组动物的逃避失败次数比正常组动物显著增加(P <0.01),丙咪嗪90 mg/kg在获得性无助后第2天～第4天均显著减少动物逃避失败次数,与模型对照组比较差异显著(P <0.01或P <0.05),表明模型复制成功.在获得性无助后第3天和第4天,巴戟天寡糖100 mg/kg可以显著减少动物逃避失败次数(第3天:6.4±2.6 vs 18.3±3.2;第4天:7.0±3.1 vs 20.1±3.1,P <0.05),巴戟天寡糖50 mg/kg在第4天显著减少逃避失败次数(8.1±2.8 vs 20.1±3.1, P <0.05).结论在大鼠获得性无助模型上,可采用口服给药途径评价药物的抗抑郁作用,并且巴戟天寡糖在此模型上口服给药时具有抗抑郁活性.