巴戟天寡糖对海马神经细胞再生及神经元生长的影响

目的:考察巴戟天寡糖对海马神经细胞再生及神经元生长的影响。方法:成年ICR小鼠随机分为生理盐水对照组、氟西汀对照组(18 mg.kg-1)和巴戟天寡糖高、低剂量组(50,25 mg.kg-1),各组连续腹腔注射14 d。采用免疫组化法测定小鼠海马齿状回新增殖神经细胞的数目;通过原代细胞培养观察不同剂量巴戟天寡糖(1.25,2.5,5,10 mg.mL-1)对大鼠海马神经元树突生长的影响。结果:巴戟天寡糖50mg.kg-1能够显著促进成年小鼠海马神经细胞的再生;10 mg.mL-1巴戟天寡糖能够增加原代培养的海马神经元树突及分支数目(P<0.05)。结论:巴戟天寡糖对海马神经可塑性具有调节作用,该作用是否是其抗抑郁作用机制之一仍需进一步证实。     

巴戟天中菊淀粉型低聚糖类单体成分对小鼠的抗抑郁作用

应用小鼠悬尾法，５－羟色胺酸诱发小鼠甩头法，阿扑吗啡诱导小鼠刻板行为法以及小鼠全脑单胺递质含量测量法等，综合评价巴戟天中的菊淀粉型低聚糖类四种单体成分的抗抑郁药理作用．实验结果表明它们在不影响小鼠自发活动的剂量下，显著缩短小鼠悬尾抑郁模型的不动时间，并兴奋５－羟色胺能神经系统，对多巴胺系统也有一定影响．其中两个单体，可使小鼠脑内的去甲肾上腺素和５－羟色胺及其代谢物羟５－吲哚乙酸显著升高，但羟色胺５－羟吲哚乙酸比值无明显变化．这一结果初步表明这些寡糖的抗抑郁作用可能主要通过５－羟色胺能神经系统起作用     

巴戟天寡糖胶囊联合阿戈美拉汀治疗老年抑郁症的临床研究

目的探讨巴戟天寡糖胶囊联合阿戈美拉汀片治疗老年抑郁症的临床疗效。方法选取2015年7月—2018年7月内蒙古自治区人民医院收治的187例老年抑郁症患者作为研究对象,所有患者根据入院顺序随机分成巴戟天寡糖胶囊组(62例)、阿戈美拉汀组(62例)和联合治疗组(63例)。巴戟天寡糖胶囊组患者口服巴戟天寡糖胶囊,1粒/次,2次/d;阿戈美拉汀组患者于睡前口服阿戈美拉汀片,1片/次,1次/d;联合治疗组采用巴戟天寡糖胶囊联合阿戈美拉汀片进行治疗,剂量与巴戟天寡糖胶囊组、阿戈美拉汀组相同。3组患者均连续治疗6周。观察3组的临床疗效,比较3组的汉密尔顿焦虑评分、汉密尔顿抑郁评分、血清肿瘤坏死因子-α(TNF-α)和白细胞介素1β(IL-1β)水平。结果治疗后,巴戟天寡糖胶囊组、阿戈美拉汀组和联合治疗组的总有效率分别为83.87%、85.48%、96.83%,组间比较差异具有统计学意义(P0.05)。治疗后,3组患者汉密尔顿焦虑评分和汉密尔顿抑郁评分均显著降低,同组治疗前后比较差异具有统计学意义(P0.05);且联合治疗组汉密尔顿焦虑评分和汉密尔顿抑郁评分显著低于巴戟天寡糖胶囊组和阿戈美拉汀组,组间比较差异具有统计学意义(P0.05)。治疗后,3组患者血清TNF-α和IL-1β水平均显著降低,同组治疗前后比较差异具有统计学意义(P0.05);且联合治疗组血清TNF-α和IL-1β水平均显著低于巴戟天寡糖胶囊组和阿戈美拉汀组,组间比较差异具具有显著性(P0.05)。结论巴戟天寡糖胶囊联合阿戈美拉汀片治疗老年抑郁症具有较好的临床疗效,能改善临床症状,调整血清因子水平,安全性较好,具有一定的临床推广应用价值。     

“助阳舒心方”及其拆方抗抑郁作用

目的:研究助阳舒心方及其拆方的抗抑郁作用。方法:运用小鼠悬尾试验(TST)、强迫游泳试验(FST),观察口服助阳舒心方及其拆方后对小鼠行为的影响。结果:助阳舒心方能显著缩短TST和FST;方中巴戟天、石菖蒲、肉桂也能缩短TST和FST。结论:助阳舒心方具有一定抗抑郁作用,方中巴戟天、石菖蒲、肉桂单用也有抗抑郁作用。     

2010-2020年巴戟天研究进展

目的:对2010-2020年期间巴戟天的研究进行整理归纳,了解其发展现状并对其发展前景进行展望。方法:通过文献研究,总结其在品种考证和资源分布、化学成分、质量标准、DNA分子条形码、炮制方法、提取工艺、含量测定等方面的研究进展。结果与结论:总结发现近10年巴戟天的研究取得了较大进展:确定了巴戟天的基原问题,探索部分化学成分的药理作用,完善巴戟天的药典标准;发现巴戟天在目前研究存在的一些难点问题,例如巴戟天的混伪品较多,建议构建巴戟天及其混伪品的基因库,有助于将其正本清源。通过对巴戟天的研究进行整理归纳为后续巴戟天的研究及开发利用提供参考,也为巴戟天药材的质量控制和药效物质基础研究奠定基础。     

巴戟天寡糖对成肌细胞增殖及分化的影响

目的：观察了巴戟天寡糖对成肌细胞增殖分化的作用，并初步探讨其机制。方法：采用离体纯化培养的乳鼠双侧后肢骨骼肌成肌细胞的方法，以常规细胞培养为正常对照、5-氮杂胞苷（10μmol／L）为阳性对照，以①成肌细胞形态学变化。②免疫组化法鉴定结蛋白（Desmin）。③免疫组化法测定转化生长因子β1（TGF-β1）和增殖细胞核抗原（PCNA）。④生长曲线的绘制。⑤MTT（Methyl Thiazolyl Tetrazolium）法检测巴戟天寡糖对成肌细胞增殖的影响为指标，观察巴戟天寡糖100μg／ml、300μg／ml、500μg／ml三种浓度对其增殖及分化的影响。结果：1．成肌细胞培养24h后可见大量折光率强的圆形细胞贴壁；48h后见大量梭形或纺锤形的单个核细胞出现；72h后梭形细胞的数量逐渐增加，成肌细胞细长，并相互拉网，细胞从单个核期进入合体细胞阶段；培养第5天后，在镜下可观察到分化状态较好的肌管有自发性搏动的收缩现象。2．成肌细胞desmin胞浆呈阳性反应，细胞核外周及胞浆呈棕黄色。3．巴戟天寡糖两组单核成肌细胞及多核初生肌管内胞浆中TGF-β1均呈阳性反应。结果表明在一定剂量范围内，巴戟天寡糖对成肌细胞内TGF-β1的表达有增强作用，过大剂量时反而抑制其表达。4．巴戟天寡糖各剂量组单核成肌细胞及初生肌管内细胞核的PCNA阳性反应均较对照组强，且随剂量递增而显强阳性反应。5．原代成肌细胞生长培养48h后开始增生，早期增殖较快，倍增时间为5d，6、7d进入平稳期。6．巴戟天寡糖以剂量方式促进成肌细胞增殖，且各组与对照组相比均有显著差异，在500μg／m剂量达到最大效应（P〈0．05）。结论：巴戟天寡糖具有明显促进成肌细胞增殖及分化的作用，可在一定剂量范围内增加成肌细胞的TGF-β1表达，但是剂量过高反而抑制其表达,其原因还需进一步深入探讨。PCNA可作为成肌细胞增殖的一种标志物。     

巴戟天寡糖胶囊在中国健康志愿者中的耐受性研究

目的：观察健康志愿者对巴戟天寡糖胶囊的耐受性,为II期临床研究提供安全有效的给药剂量及方案。方法：根据改良Black well法,起始剂量为50 mg。共入选健康受试者42例,其中单剂量组的32例受试者分别接受了6个剂量组（50 mg组2例、150 mg组4例、300 mg组6例、600 mg组6例、800 mg组8例和1 000 mg组6例）的单剂量巴戟天寡糖胶囊治疗;连续给药剂量组的10例受试者接受800 mg&#8226;d-1,qd,连续服药7 d的巴戟天寡糖胶囊治疗。分别比较了单次给药和连续给药前后受试者的生命体征、心电图和实验室检查结果的变化,单次服药和连续服药后观察到的不良事件和受试者报告的不良反应。结果：42例受试者全部完成研究,且未出现具有临床意义异常的生命体征、心电图和实验室检查结果,主要的不良反应为口干、疲乏、困倦,与剂量相关,程度轻微。结论：本研究中的中国健康受试者对50~1 000 mg&#8226;d-1的巴戟天寡糖胶囊具有良好的耐受性。     

巴戟天属植物中环烯醚萜类化合物研究进展

摘要：环烯醚萜类化合物广泛存在于巴戟天属植物中,具有抗抑郁、镇痛抗炎、骨保护、抗衰老、抗肿瘤、保护心血管和抗菌等作用。本文总结了巴戟天属植物中环烯醚萜类化合物的种类、结构、药理活性及含量检测方法,对分析巴戟天属植物中环烯醚萜类成分的物质基础和作用机制具有重要的意义。     

巴戟天寡糖胶囊用于轻、中度抑郁症患者巩固期治疗的临床研究

目的 观察巴戟天寡糖胶囊用于治疗轻、中度抑郁症患者的24周巩固期的疗效和安全性。方法 本研究采用开放、单臂、多中心设计,纳入已完成巴戟天寡糖急性期治疗的成人轻、中度抑郁症患者,继续给予巴戟天寡糖胶囊24周,巩固期维持治疗剂量不变,用汉密尔顿抑郁量表(HAMD-17)、汉密尔顿焦虑量表(HAMA)、临床总体印象量表-严重度(CGI-S)和亚利桑那性体验量表(ASEX)评估治疗前后的变化,评估患者的缓解率、复燃率及复燃时间,观察患者治疗相关不良事件的发生情况。结果 治疗前后患者的HAMD-17评分分别为(6.60±1.87)和(5.85±4.18)分,HAMA评分分别为(6.36±3.02)和(4.93±3.09)分,CGI-S评分分别为(1.49±0.56)和(1.29±0.81)分,ASEX评分分别为(15.92±4.72)和(15.57±5.26)分,在统计学上差异均有统计学意义(均P<0.05)。用药24周末,患者的缓解率为54.59%(202例/370例),复燃率为6.49%(24例/370例),复燃时间为(64.67±42.47) d。巴戟天寡糖胶囊药物不良反应发生率为1...     

巴戟天寡糖对鼠强迫性游泳和获得性无助抑郁模型的影响

为了深入和全面地评价巴戟天寡糖 (MOs)的抗抑郁作用 ,本研究观察了不同批次的MOs对大鼠 ,小鼠强迫性游泳和大鼠获得性无助抑郁模型的影响 .结果显示 ,3批MOs在 2 0～ 5 0mg·kg- 1(ip或po)剂量范围内显著缩短大鼠和小鼠强迫性游泳期间的不动时间 ,其剂量效应均显示行为药理学所特有的U型曲线 .不同批次的MOs有效剂量均非常接近 .在大鼠获得性无助抑郁模型 ,MOs 6 0～ 10 0mg·kg- 1(ip ,每天 2次 ,连续 8次 )显著减少大鼠的逃避失败次数 ,6 0mg·kg- 1还明显减少逃避失败动物数 .这些结果进一步表明MOs具有抗抑郁作用     

巴戟天对骨代谢相关作用的实验研究进展

综述巴戟天对骨代谢的作用研究进展，为进一步研究提供新的思路。巴戟天中有效成分可促进骨髓基质细胞增殖、促进成骨细胞增殖并抑制其凋亡、抑制破骨细胞骨吸收作用。并且巴戟天中含有多种骨代谢所必需的微量元素。应加强巴戟天体内作用试验的研究。     

栀子厚朴汤抗抑郁活性成分的研究

目的：研究经典方剂栀子厚朴汤中具有抗抑郁作用的活性成分。方法：在栀子厚朴汤原方基础上,采用正交设计获得药味数及各味药的用量不同的16个组方,分别给随机分组的16组小鼠灌胃使用,测定小鼠在悬尾实验和强迫游泳实验中的不动时间,并据此计算正交表中栀子、厚朴和枳实的极差,确定栀子厚朴汤中具有抗抑郁作用的主要药材;对各组方进行HPLC分析,选出20个特征色谱峰,通过相关分析,得出各特征峰峰面积与不动时间的皮尔森相关系数,寻找与药效相关性较大的色谱峰,探讨栀子厚朴汤抗抑郁活性成分。结果：确定厚朴为栀子厚朴汤发挥抗抑郁作用的关键药材;发现6个来自厚朴的色谱峰（即4、5、7、18、19、20号峰）的峰面积与药效相关性较强,其对应的成分为栀子厚朴汤抗抑郁活性成分。结论：采用将HPLC分析、药理学实验及化学计量学方法,如极差分析、相关分析相结合的研究方法,可发现栀子厚朴汤的活性成分,并对其他中药复方活性成分的确认具有一定的参考价值。     

巴戟天寡糖联合帕罗西汀治疗抑郁症临床评价

目的 探讨巴戟天寡糖胶囊联合帕罗西汀治疗抑郁症的疗效及对神经递质和炎性因子水平的影响。方法 选取青岛市市立医院2015年2月至2018年12月收治的抑郁症患者143例,按随机数字表法分为对照组(71例)和研究组(72例)。两组患者均予帕罗西汀治疗,研究组患者加用巴戟天寡糖胶囊,均治疗8周。结果 研究组总有效率为70.83%,明显高于对照组的54.93%(P<0.05);治疗后,两组患者的去甲肾上腺素(NE)、5-羟色胺(5-HT)、脑源性神经营养因子(BDNF)水平均明显升高(P<0.05),神经生长因子(NGF)及白细胞介素6(IL-6)、白细胞介素12(IL-12)、肿瘤坏死因子-α(TNF-α)水平均明显降低(P<0.05),且研究组均明显优于对照组(P<0.05);研究组不良反应发生率与对照组相当(20.83%比15.49%,P>0.05)。结论 巴戟天寡糖胶囊联合帕罗西汀治疗抑郁症,可有效改善患者神经内分泌功能和炎性状况。     

Brain Functional Effects of Psychopharmacological Treatment in Major Depression: A Focus on Neural Circuitry of Affective Processing

In the last two decades, neuroimaging research has reached a much deeper understanding of the neurobiological underpinnings of major depression (MD) and has converged on functional alterations in limbic and prefrontal neural networks, which are mainly linked to altered emotional processing observed in MD patients. To date, a considerable number of studies have sought to investigate how these neural networks change with pharmacological antidepressant treatment. In the current review, we therefore discuss results from a) pharmacological functional magnetic resonance imaging (fMRI) studies investigating the effects of selective serotonin or noradrenalin reuptake inhibitors on neural activation patterns in relation to emotional processing in healthy individuals, b) treatment studies in patients with unipolar depression assessing changes in neural activation patterns before and after antidepressant pharmacotherapy, and c) predictive neural biomarkers of clinical response in depression. Comparing results from pharmacological fMRI studies in healthy individuals and treatment studies in depressed patients nicely showed parallel findings, mainly for a reduction of limbic activation in response to negative stimuli. A thorough investigation of the empirical findings highlights the importance of the specific paradigm employed in every study which may account for some of the discrepant findings reported in treatment studies in depressed patients.     

正交试验优选巴戟天低聚糖提取工艺

目的：优选巴戟天中低聚糖提取工艺。方法：采用紫外-可见分光光度法,以低聚糖含量和总固体得率为指标,以醇浓度、提取时间、提取次数、加液量为考察因素,采用正交试验优选巴戟天中低聚糖提取工艺。结果：最佳提取工艺为50%乙醇加热回流提取2次,分别加13倍、11倍药材量,每次2h。结论：优选工艺合理、可行,提取率高,可用于巴戟天中低聚糖的提取。     

Recent progress in pharmacological and non-pharmacological treatment options of major depression

In spite of recent progress in the pharmacotherapy of depression major issues are still unresolved. These include the non-response rate of approximately 30% to conventional antidepressant pharmacotherapy, side effects of available antidepressants and the latency of several weeks until clinical improvement. The only non-pharmacological biological treatment options available so far which exert more rapid antidepressant efficacy are electroconvulsive therapy and, as an augmentation strategy, sleep deprivation. Current pharmacological treatments aim to enhance serotonergic and/or noradrenergic neurotransmission. In spite of emerging knowledge, the crucial mechanisms underlying both non-pharmacological treatments, which are responsible for antidepressant efficacy, are not yet clear so far. In the meantime several new pharmacological principles are under investigation with regard to their putative antidepressant potency. These include 5-HT1A receptor agonists, tachykinin receptor antagonists and various interventions within the hypothalamic-pituitary-adrenal system. While there is evidence for antidepressant properties of these new treatments in animal studies, in case series, in open studies and to some degree also in placebo controlled studies, no definite proof for the antidepressant efficacy of these new pharmacological strategies according to the requirements for evaluation of antidepressant drugs has been furnished so far. In contrast, for the established non-pharmacological treatment strategies including bright light therapy the clinical efficacy has been proven at least in subgroups of depression, but more knowledge of the main mechanisms underlying their antidepressant efficacy is still necessary. In addition new non-pharmacological treatments like repetitive transcranial magnetic stimulation, magnetic seizure therapy and Vagus nerve stimulation are currently under development. Nevertheless, a follow-up of both the new pharmacological strategies and non-pharmacological treatment options is of major importance to provide even better strategies for the clinical management of depression, which also is of great socio-economic impact.     

Pyrrolobenzodiazepines and related systems. 2. Synthesis and biological properties of isonoraptazepine derivatives.

The synthesis of some derivatives and analogues of 12,13,14,14a-tetrahydro-9H,11H-pyrazino-[2,1-c]pyrrolo[1,2- a][1,4]benzodiazepine (isonoraptazepine) is reported. The new derivatives have been subjected to pharmacological tests for evaluation of antidepressant effects. Neurobehavioral assays were also carried out to acquire data on neurotoxicity and sedative action. Isonoraptazepine analogues and derivatives lacked the pharmacological activity of mianserin and aptazepine and showed properties similar to imipramine. Molecular modeling studies revealed structural similarities between isonoraptazepine derivatives and imipramine, thus explaining the similar pharmacological profile found in some of the tests employed. Based on pharmacological data the title compounds cannot be regarded as alpha 2 presynaptic adrenoceptors antagonists. In vitro studies for receptor binding gave support to this observation. The above studies lead us to conclude that isonoraptazepine derivatives are conformationally restricted analogues of imipramine, but their antidepressant activity cannot be correlated to inhibition of 5HT uptake. Among the derivatives tested, 7b and 8e show some affinity for the d-fenfluramine receptor site, a serotonin presynaptic site connected with anorectic activity.     

VEGF regulates antidepressant effects of lamotrigine

The anticonvulsant drug lamotrigine has been shown to produce strong antidepressant effects in the treatment of bipolar disorder patients. Our previous studies have demonstrated that brain derived neurotrophic factor (BDNF) signaling plays an important role in regulating its behavioral actions in several rodent models of depression. The current study extends earlier work on BDNF and explores the role of another important neurotrophin vascular endothelial growth factor (VEGF) in regulating the antidepressant actions of lamotrigine. The results showed that chronic administration of 30 mg/kg lamotrigine (14 days) normalized the down-regulated frontal and hippocampal VEGF protein expression as well as the behavioral deficits induced by chronic unpredictable stress. In addition, pharmacological inhibition of VEGF signaling by infusion of SU5416, a selective Flk-1 receptor inhibitor, blocks the antidepressant effects of lamotrigine in all behavioral paradigms. Taken together, this study provides further evidence that VEGF is also an essential regulator for the antidepressant effects of lamotrigine.     

Efficacy and tolerance profile of agomelatine and practical use in depressed patients

Agomelatine is a new agent with a unique pharmacological profile, as the first melatonergic antidepressant. Its antidepressant efficacy has been demonstrated in the treatment of major depressive disorder (MDD) at a dose of 25 mg/day. Expectations from antidepressant therapies now go beyond efficacy alone, to include advantages in tolerability and safety. Due to its pharmacological profile, agomelatine does not induce the side-effects typical of other therapies, such as selective serotonin reuptake inhibitors (i.e. gastrointestinal disorders, weight gain, serotonergic syndrome and insomnia). Moreover, a placebo-controlled trial in MDD comparing the effects of agomelatine and venlafaxine on sexual dysfunction (another significant side-effect with current antidepressant medications) indicated the very favourable profile of agomelatine; in the same study, there was similar antidepressant efficacy in the same two groups. A double-blind, placebo-controlled trial investigating the effect of abrupt cessation of treatment demonstrated the absence of discontinuation symptoms with agomelatine, which was in contrast with the results observed with paroxetine. The ability of an antidepressant to relieve sleep complaints with no sedative effects is a key advantage because sleep complaints are a major presenting feature of depression. Again due to its unique pharmacological profile, agomelatine has been shown to positively influence disturbed circadian rhythms in depressed patients by significantly improving all phases of disturbed sleep and the overall quality of sleep, with a favourable impact on daytime alertness. In conclusion, experience with agomelatine across a range of clinical studies suggests that this compound offers a novel approach to the treatment of depression combining efficacy, even in severe depression, with an extremely favourable side-effect profile and sleep regulation. These properties give agomelatine a definite clinical advantage in the treatment of depression.     

The inhibitory effects of aqueous extract of Magnolia officinalis on human mesangial cell proliferation by regulation of platelet-derived growth factor-BB and transforming growth factor-beta1 expression

Mesangial cell (MC) proliferation, mediated by platelet-derived growth factor (PDGF)-BB, transforming growth factor (TGF)-beta1, and cyclin-dependent kinases (CDK), is the common feature of glomerulosclerosis. Magnolia officinalis, stem bark of Machilus thunbergii S., has multiple pharmacological effects. In this study, we investigated the influence of aqueous extract of Magnolia officinalis on MC proliferation, DNA synthesis, and expression of PDGF-BB, TGF-beta1, CDK1, CDK2, and CDK4 in fetal bovine serum (FBS)-activated human MC. Magnolia officinalis inhibited the MC proliferation, DNA synthesis, and the expression of PDGF-BB, CDK1, and CDK2 gene and CDK1, CDK2, and TGF-beta1 protein. These results suggest that the inhibitory effect of Magnolia officinalis on MC proliferation may be mediated by regulation of PDGF-BB and TGF-beta1expressions and by modulation of CDK1 and CDK2 expression.