小柴胡汤化学成分及其在抑郁模型大鼠体内代谢成分的分析

目的采用UPLC-MS/MS技术分析小柴胡汤提取液化学成分及其在抑郁模型大鼠体内的代谢产物,为其抗抑郁作用药效物质研究奠定基础。方法采用Acquity UPLCTMBEH C18柱进行色谱分离,以乙腈-0.1%甲酸水溶液为流动相进行梯度洗脱,以电喷雾质谱检测,扫描范围为m/z 150～1 500,在正负离子同时扫描的模式下,通过获得一、二级质谱信息,参照对照品及相关文献信息,确定小柴胡汤的化学成分及其在抑郁模型大鼠体内的代谢产物的可能结构。结果小柴胡汤样品中共检测到44个化学成分。抑郁模型大鼠ig给予小柴胡汤后,在血清样品中共检测出7个原形成分和8个代谢产物;在尿液样品中共检测出12个原形成分和19个代谢产物。结论建立的UPLC-MS/MS法能较全面地分析小柴胡汤的化学成分及其在抑郁模型大鼠体内的代谢产物,为进一步研究小柴胡汤抗抑郁作用药效物质基础提供依据。     

基于网络药理学的香附抗抑郁作用机制研究

目的 基于网络药理学方法研究香附多成分-多靶点-多途径的抗抑郁潜在作用机制。方法 通过中药系统药理学分析平台（TCMSP）数据库、文献挖掘和本实验室已有研究收集香附化学成分，并依据类药原则进行筛选。使用PhamMapper和DrugBank数据库进行靶点预测和筛选，通过MAS 3.0及KEGG通路注释分析香附抗抑郁效应化学成分的作用通路，采用Cytoscape 3.6.1软件构建"化合物-核心靶点-通路"网络，预测其抗抑郁药效成分及相关作用靶点。结果 香附中的69个化合物作用于103个靶点，29个核心靶点。构建的"化合物-核心靶点-代谢通路"网络预测发现，香附中48个化学成分直接或间接作用于15个核心靶点，8条抑郁相关代谢通路，主要涉及细胞过程、对应激的应答等生物过程，通过调节黏附斑、神经营养因子、血管内皮生长因子（VEGF）、促性腺激素释放激素（GnRH）、NOD样受体、胰岛素、趋化因子、ErbB信号通路发挥抗抑郁作用。结论 网络药理学分析结果初步揭示了香附以多成分、多靶点、多通路的协同作用方式发挥抗抑郁效应机制。     

躯体形式障碍的诊断和治疗

Patientswithsomaticdisorderoftencomplaintsindisposition,whereasphysicalandassistexaminationshowednoorganiclesion.Evensomephysicalabnormalitycannotexplainsymptomsanddistress.1Subjectsandmethod1.1SubjectsDuring1999～2000,68outpatientsandinpa-tientscomplainedofindispositionwithoutorganiclesionafterphysicalexaminationorthosewithpooreffectaftervarioustherapywereadoptedinpsychiatricoutpatientdepartment.Thesepatientsincluded27menand41womenaged8-73years,meanage:(36.5±7.2).Educationtimelastedform1-17…     

绿萼梅总黄酮对小鼠抑郁的改善作用

目的研究绿萼梅总黄酮对小鼠的抗抑郁作用。方法采用昆明种小鼠随机分为对照组、阿米替林或氟西汀(20 mg/kg)组、绿萼梅总黄酮(120、240、360 mg/kg)组,每小组各12只,每天ig给药1次。通过小鼠强迫游泳实验、悬尾实验、利血平诱导眼睑下垂和体温降低模型、5-羟基色氨酸(5-HTP)诱导小鼠甩头模型,考察绿萼梅总黄酮的影响。结果绿萼梅总黄酮各剂量均能显著缩短小鼠强迫游泳、悬尾不动时间(P0.05、0.01);绿萼梅总黄酮240、360 mg/kg能显著抑制利血平诱导的小鼠眼睑下垂和体温降低(P0.05、0.01),同时能显著增强5-HTP诱导的小鼠甩头次数(P0.05、0.01)。结论绿萼梅总黄酮对小鼠各模型有抗抑郁的作用。     

百合的化学成分及药理作用研究进展

百合是一种药食同源的中药,在我国资源丰富,分布广泛,具有较高的开发利用价值。目前研究发现,百合含有甾体皂苷、多糖、酚酸甘油酯、生物碱、黄酮、氨基酸、磷脂及其他烷烃等成分,主要为多糖及甾体皂苷。药理研究表明,其具有抗肿瘤、抗抑郁、抗氧化、降血糖、抗疲劳与耐缺氧、免疫调节,抗炎,抑制Na+/K+ATP酶等作用。百合可抑制多种癌细胞增殖,并促进其凋亡,主要活性成分为多糖、甾体皂苷及生物碱。其中甾体皂苷还是百合抗抑郁的活性成分。笔者通过检索中国知网,万方,Science Direct,Pub Med,Web of Science等数据库,对近30年有关百合的化学成分及药理作用的文献,进行整理,分析和总结,系统地综述了百合化学成分及药理作用的研究进展,旨在为百合的深入研究和开发利用提供理论参考。     

基于LC-MS技术的柴胡石油醚部位对抑郁症模型大鼠海马组织的代谢组学研究

目的柴胡石油醚部位具有显著的抗抑郁活性,研究抑郁症模型大鼠给予柴胡石油醚部位后海马组织的代谢物谱,明确其发挥药效的代谢调控通路。方法采用基于UHPLC-Q Exactive Orbitrap-MS代谢组学方法研究海马组织的整体代谢轮廓,分析柴胡石油醚部位抗抑郁作用的代谢调控机制。结果柴胡石油醚部位通过调节氨基酸代谢和能量代谢改善抑郁状态,但对正常机体海马组织的代谢轮廓并未产生显著影响。结论为柴胡石油醚部位抗抑郁作用潜在分子机制的研究提供了借鉴。     

逍遥散中当归的抗抑郁活性成分的研究

目的指认逍遥散中君药当归对复方抗抑郁有效部位的贡献成分,并筛选其中潜在的抗抑郁活性成分。方法采用UPLC-PDA技术对逍遥散抗抑郁有效部位及当归相应部位的指纹图谱进行匹配,通过对比色谱峰的保留时间及全波长紫外光谱图,归属当归对逍遥散抗抑郁有效部位的贡献成分。运用多种色谱方法对贡献成分进行导向分离,采用现代谱学技术鉴定化合物的结构,并对分离得到的化合物进行体外活性验证。结果共归属并鉴定出当归对逍遥散抗抑郁有效部位的贡献成分5个,分别为阿魏酸松柏醇酯(1)、E-丁烯基苯酞(2)、藁本内酯(3)、Z-丁烯基苯酞(4)、12-异戊烯酰基-14-乙酰基-2E,8E,10E-三烯-4,6-二炔-1-醇(5),其中化合物5为首次从伞形科植物中分离得到。化合物1、3、4能有效保护谷氨酸损伤的SH-SY5Y和PC12细胞。结论 UPLC-PDA导向分离技术可快速、准确指认复方来源于其单味药材的贡献成分。阿魏酸松柏酯、藁本内酯、Z-丁烯基苯酞可能为当归贡献逍遥散抗抑郁作用的活性成分。     

An Investigation of the Antidepressant Action of Xiaoyaosan in Rats Using Ultra performance Liquid Chromatography–Mass Spectrometry Combined with Metabonomics

A rapid, highly sensitive, and selective method was applied in a non‐invasive way to investigate the antidepressant action of Xiaoyaosan (XYS) using ultra performance liquid chromatography–mass spectrometry (UPLC‐MS) and chemometrics. Many significantly altered metabolites were used to explain the mechanism. Venlafaxine HCl and fluoxetine HCl were used as chemical positive control drugs with a relatively clear mechanism of action to evaluate the efficiency and to predict the mechanism of action of XYS. Urine obtained from rats subjected to chronic unpredictable mild stress (CUMS) was analyzed by UPLC‐MS. Distinct changes in the pattern of metabolites in the rat urine after CUMS production and drug intervention were observed using partial least squares–discriminant analysis. The results of behavioral tests and multivariate analysis showed that CUMS was successfully reproduced, and a moderate‐dose XYS produced significant therapeutic effects in the rodent model, equivalent to those of the positive control drugs, venlafaxine HCl and fluoxetine HCl. Metabolites with significant changes induced by CUMS were identified, and 17 biomarker candidates for stress and drug intervention were identified. The therapeutic effect of XYS on depression may involve regulation of the dysfunctions of energy metabolism, amino acid metabolism, and gut microflora changes. Metabonomic methods are valuable tools for measuring efficacy and mechanisms of action in the study of traditional Chinese medicines. Copyright © 2012 John Wiley & Sons, Ltd.     

Effects of Mulberry on The Central Nervous System: A Literature Review

Background Mulberry, including several species belonging to genus Morus, has been widely used as a traditional medicine for a long time. Extracts and active components of mulberry have many positive neurological and biological effects and can become potential candidates in the search for new drugs for neurological disorders.Objectives We aimed to systematically review the medical literature for evidence of mulberry effects on the central nervous system.Methods We conducted a systematic search in nine databases. We included all in vivo studies investigating the effect of mulberry on the central nervous system with no restrictions.Results We finally included 47 articles for quality synthesis. Our findings showed that mulberry and its components possessed an antioxidant effect, showed a reduction in the cerebral infarct volume after stroke. They also improved the cognitive function, learning process, and reduced memory impairment in many animal models. M. alba and its extracts ameliorated Parkinson''s disease-like behaviors, limited the complications of diabetes mellitus on the central nervous system, possessed anti-convulsant, anti-depressive, and anxiolytic effects.Conclusion Mulberry species proved beneficial to many neurological functions in animal models. The active ingredients of each species, especially M. alba, should be deeper studied for screening potential candidates for future treatments.     

南柴胡和北柴胡组成的逍遥散抗抑郁作用的1H-NMR代谢组学研究

目的 比较不同品种柴胡（南柴胡和北柴胡）组成的逍遥散的抗抑郁功效,探寻其对大鼠内源性代谢产物变化规律的影响。方法 采用慢性温和不可预知应激程序对大鼠进行为期4周的抑郁造模,在造模2周后分别ig给予由南柴胡或北柴胡组成的逍遥散（生药）46 g/kg水提取液、文拉法辛0.05 g/kg干预,每天1次,连续给药2周,观测动物行为学症状。应用核磁共振（¹H-NMR）方法分析大鼠血清内源性代谢产物的变化规律。结果 2种逍遥散和文拉法辛对抑郁大鼠行为学指标均有显著影响,与模型组比较差异显著（P＜0.05、0.01）。代谢组学研究结果显示,2种逍遥散和文拉法辛干预后,大鼠血清中异亮氨酸、氧化三甲胺、胆碱水平升高,而乳酸、N-乙酰糖蛋白、肌酸、苏氨酸及β-葡萄糖等水平降低,与模型组比较差异显著（P＜0.05、0.01）。2个逍遥散组对抑郁大鼠行为学指标的影响组间比较未显示统计学差异。结论 不同品种柴胡组成的逍遥散均具有明显的抗抑郁作用,但功效有所差别,即南柴胡组成逍遥散的抗抑郁效果及起效时间略优于北柴胡。应用行为学与代谢组学相结合的方法评价逍遥散抗抑郁功效具有准确性好、灵敏度高等特点。