Comprehensive metabolic profiling of Alismatis Rhizoma triterpenes in rats based on characteristic ions and a triterpene database

Alismatis Rhizoma(AR)is widely used in Chinese medicine,and its major bioactive components,triterpenes,reportedly possess various pharmacological activities.Therefore,it is very important to study the metabolism of triterpenes in vivo.However,the metabolism of AR triterpene extract has not been comprehensively elucidated due to its complex chemical components and metabolic pathways.In this study,an ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry method,which was based on the characteristic ions from an established database of known triterpenes,was used to analyze the major metabolites in rats following the oral administration of Alismatis Rhizoma extracts(ARE).As a result,a total of 233 constituents,with 85 prototype compounds and 148 metabolites,were identified for the first time.Hydrogenation,oxidation,sulfate and glucuronidation conjugation were the major metabolic pathways for triterpenes in AR.In addition,the mutual in vivo transformation of known ARE triterpenes was discovered and confirmed for the first time.Those results provide comprehensive insights into the metabolism of AR in vivo,which will be useful for future studies on its pharmacodynamics and pharmacokinetics.Moreover,this established strategy may be useful in metabolic studies of similar compounds.

Research Status of Chinese Medicinal Herbs Zexie (Rhizoma Alismatis) and Its Enlightenment to TCM Development in Guangxi

In this paper,the scientific research status of Zexie(Rhizoma Alismatis)was comprehensively expounded from the aspects of plant characteristics,source,chemical composition,pharmacological research and quality control methods,etc.The market situation of Rhizoma Alismatis was systematically analyzed from historical and current perspectives;aiming at the problems of poor quality and irregular processing of Chinese medicinal herbs Rhizoma Alismatis,some ideas were put forward to improve the quality and market value of medicinal materials of Rhizoma Alismatis,so as to make the Chinese herbal medicine industry develop towards a healthy and efficient direction.

Towards a better understanding of the therapeutic potential of Rhizoma Alismatis: A phytochemical and pharmacological review

Rhizoma Alismatis(RA),the dried rhizome of Alisma orientalis(Sam.)Juzep,isa widely used traditional herbal medicine popularly known as″Ze Xie″in Chinese.RA is an important crude herb component of several famous Chinese preparations including Zexie decoction,Liu Wei Di Huang pills,Wu Ling power and so on.It has been used to treat various ailments such as dysuria,edema,nephropathy,hypertension,hyperlipidemia and diabetes,etc.A wide range of chemical compounds mainly triterpenes,diterpenes and sesquiterpenes have been isolated from RA,among which the protostane-type triterpenes termed alisols attract the most attention owing to their unique chemical structure and various biological activity.The extract and active compounds of RAhave been demonstrated to possess a wide spectrum of pharmacological effects which support its clinical use,e.g.diuretic,hypoglycemic,hypolipidemic,hepatoprotective,preventing bone loss,anti-inflammatory andantivirus activities.In our previous studies,we have investigatedthe anti-proliferative activities of terpenoids isolated from RA and their structure-activity relationships.Alisol B 23-acetate was demonstrated to induce G1 phase cell cycle arrest and apoptosis,and inhibit migration and invasion of ovarian cancer cells.The present paper reviews the up-to-date information concerning the ethnopharmacology,phytochemistry,pharmacology and toxicology of RA.This information will be helpful for a better understanding of therapeutic potential of RA as wel as the further explorations.

《神农本草经》与经方应用之泽泻篇

《神农本草经》记载泽泻“:味甘,寒。主风寒湿痹,乳难,消水,养五脏,益气力,肥健。久服耳目聪明,不饥,延年,轻身,面生光,能行水上。”以《神农本草经》中泽泻的主治作用为线索,分析《伤寒杂病论》中泽泻的应用。泽泻主治消水,消心下之水,常与白术配伍,以泽泻汤为代表方;消膀胱之水,常与茯苓、白术、桂枝等药配伍,以五苓散为代表方;消腰下之水,常与牡蛎、栝楼根、葶苈子等药配伍,以牡蛎泽泻散为代表方;消肾脏之水,常与生地黄、山茱萸等药配伍,以肾气丸为代表方;消血中之水,常与当归、芍药等药配伍,以当归芍药散为代表方。泽泻可调养五脏,培补正气,“养五脏,益气力,耳目聪明”,常与生地黄、山药等配伍,以肾气丸为代表方;“轻身,面生光,能行水上”,常与茯苓、甘草、桂枝等药配伍,以茯苓泽泻汤为代表方。

基于高分辨液质联用技术与网络药理学探讨泽苓定眩汤物质基础

目的:采用高分辨液质联用技术结合网络药理学分析泽苓定眩汤作用靶点,同时与基于药材饮片的网络药理学预测作用靶点比较。方法:采用Q-Orbitrap高分辨液质联用技术对苓定眩汤复方制剂进行天然产物成分鉴定,并对其结构进行解析,使用pharmmapper数据库和Uniprot数据库对具有3D结构的化合物进行检索,获取对应的蛋白质及靶点信息。将上述数据库所得靶点信息进行合并,从而得到基于天然产物成分鉴定所筛选出化合物所对应的靶点集合(集合A)。使用中药系统药理学数据库与分析平台(Traditional Chinese Medicine Systems Pharmacology Database and A-nalysis Platform,TCMSP)数据库收集泽苓定眩汤组方中各药材已报道有效成分及对应靶点信息,并采用上述相同方法获取组方药材对应的已知靶点集合(集合B)。将集合A和集合B取交并集,采用蛋白相互作用分析数据库STRING绘制蛋白质-蛋白质相互作用(protein-protein interaction,PPI)网络图,利用Metascape平台对基因进行富集分析。结果:采用高分辨液质联用技术对泽苓定眩汤复方制剂进行天然产物成分鉴定,共得到582个化合物,其中与数据库比对匹配程度得分≥80分的化合物共计93个,在Pubchem中可检索到64个化合物的3D结构,基于天然产物筛选出的化合物所对应的靶点共计550个。将泽苓定眩汤中七味药材使用TCMSP数据库可得到157个靶点,其预测出的靶点数量明显少于基于天然产物成分鉴定所得靶点数量,两者交集靶点共计55个。基因本体(gene ontology,GO)功能富集分析共得到519条富集结果,其中包含55个经典通路,京都基因与基因组百科全书(kyoto ency-clopedia of genes and genomes,KEGG)富集结果得到140条代谢通路。结论:采用高分辨液质联用技术结合网络药理学所得到的泽苓定眩汤靶点和富集结果更加全面。

泽泻主要化学成分及药理作用研究进展

泽泻是我国的传统中药材,其药用历史悠久,临床应用十分广泛,具有利水渗湿、化浊降脂等作用。泽泻的化学成分主要包括三萜类、倍半萜类、苯丙素类、二萜类、糖类和挥发油等多种成分。泽泻的药理作用主要包括利尿、抗肿瘤、抗炎和调脂,对糖尿病、肝病及骨质疏松等疾病具有良好的治疗作用。本文对泽泻的主要化学成分和药理作用的相关研究进展进行综述,旨在为泽泻的深入研究开发和临床应用提供一定的参考。

泽泻活性成分改善非酒精性脂肪性肝病的作用机制进展

目的为临床应用泽泻活性成分防治非酒精性脂肪性肝病(NAFLD)提供参考。方法采用计算机检索中国知网(CNKI)和PubMed数据库中泽泻活性成分改善NAFLD的相关研究及临床应用的相关文献,检索时限为自建库起至2023年8月,从药理学作用总结泽泻活性成分改善NAFLD的作用机制,并探讨其临床应用的可行性。结果泽泻活性成分Alisol A 24-acetate,Alisol B 23-acetate,Alisol F,Alismol,Alisol A,Alisol B可通过改善胰岛素抵抗、改善脂质代谢、调控胆固醇稳态、抗氧化应激反应、抗炎、调节肠道菌群等方面来改善NAFLD。泽泻复方制剂用于治疗NAFLD的疗效良好,尤其联用其他中药可进一步增强疗效。结论泽泻及其活性成分有防治NAFLD的潜力,但需要更多临床研究证实其安全性、有效性及作用机制。

基于网络药理学探讨茯苓-泽泻药对治疗慢性肾炎的作用机制

目的 基于网络药理学方法探讨茯苓-泽泻药对治疗慢性肾炎的物质基础及作用机制。方法 通过TCMSP获取茯苓-泽泻药对的活性成分,并在PharmMapper平台预测活性成分的作用靶点;运用Cytoscape3.8.2软件构建“活性成分-靶点”网络;检索GeneCards、OMIM数据库获取慢性肾炎相关靶点;采用Venny2.1在线作图工具平台构建韦恩图,得到药物与疾病交集靶点;采用STRING数据库构建交集靶点蛋白质-蛋白质相互作用网络,利用Cytoscape3.8.2软件及CytoNCA插件筛选关键靶点;借助DAVID数据库对关键靶点进行GO功能和KEGG通路富集分析。结果 获得茯苓-泽泻药对活性成分25个,作用靶点89个,慢性肾炎相关靶点1 240个,交集靶点31个,关键靶点15个。主要活性成有茯苓新酸A、泽泻醇C、茯苓新酸B、去氢茯苓酸等,关键靶点包括ALB、EGFR、SRC、CASP3等。关键靶点GO功能富集分析得到106个相关条目,生物过程主要富集于脂质和动脉粥样硬化、内分泌抵抗、肺癌蛋白多糖等;KEGG通路富集得到81条信号通路,主要涉及血管内皮生长因子(VEGF)信号通路、肿瘤坏死因子(TNF)信号通路、白细胞介素-17(IL-17)信号通路等。结论 茯苓-泽泻药对可能通过ALB、EGFR、SRC等靶点,调控VEGF信号通路、TNF信号通路、IL-17信号通路等,发挥抗炎、抗氧化、调节细胞凋亡、抑制肾小球系膜细胞增生、延缓肾纤维化进展等药理作用治疗慢性肾炎。

多指标综合评价泽泻的炮制工艺

目的:多指标综合评价泽泻的炮制工艺。方法:采用HPLC法测定不同炮制工艺盐泽泻中23-乙酰泽泻醇B、23-乙酰泽泻醇C含量,结合外观性状、显微观察评价泽泻的炮制工艺。结果:盐泽泻的最佳炮制工艺为生泽泻片先拌盐水后炒药,盐水比2%,渗入均匀后,闷润2h, 150~160℃下炒制20min。结论:该盐炙工艺可为保障我院盐泽泻饮片的质量及制剂稳定提供参考。

探讨原发性高血压运用泽泻中药汤辅助西药治疗的疗效

目的 分析原发性高血压运用泽泻中药汤辅助西药治疗的疗效。方法 选取2022年6月—2023年6月本院收治的60例原发性高血压患者进行研究,将其随机分为观察组(30例,泽泻中药汤辅助西药治疗)与对照组(30例,西药治疗)。分析患者临床疗效、血压水平变化、中医症状积分。结果 观察组患者临床疗效显著高于对照组,组间差异有统计学意义(P<0.05);观察组患者DBP、SBP、中医症状积分显著低于对照组,组间差异有统计学意义(P<0.05)。结论 原发性高血压患者采用泽泻中药汤辅助西药治疗可显著提高临床疗效,改善患者血压水平,降低患者中医症状积分,对改善患者预后具有重要的影响,值得广泛推广。

基于响应面法结合总评归一法优化泽泻趁鲜切制加工工艺

基于响应面法结合总评归一法优选泽泻趁鲜切制加工工艺。以外观性状和加工能耗为评价指标,采用单因素实验筛选出影响泽泻趁鲜切制加工工艺因素的中心点。在单因素实验基础上,以醇溶性浸出物、总三萜、总多糖、23-乙酰泽泻醇B、23-乙酰泽泻醇C、24-乙酰泽泻醇A和泽泻醇B含量的总评归一值为评价指标,以水分含量(30%、40%、50%)、切片厚度(3、4、5 mm)、干燥温度(40、50、60℃)为考察因素,根据响应面实验原理,设计三因素三水平响应面实验优化泽泻趁鲜切制加工工艺。最终获得泽泻趁鲜切制加工最佳工艺条件为水分含量40%,切片厚度4 mm,干燥温度50℃。响应面法优选泽泻趁鲜切制加工工艺切实可行,具有较强的实际意义,优选的趁鲜切制加工工艺简便、稳定,为泽泻趁鲜切制加工生产提供了科学依据。

PMP柱前衍生反相高效液相色谱—紫外检测法结合离子色谱—脉冲安倍法测定不同产地泽泻多糖的单糖组成

本文建立了1-苯基-3-甲基-5-吡唑啉酮(PMP)柱前衍生高效液相色谱-紫外检测法结合离子色谱-脉冲安倍法测定泽泻中10种单糖含量的测定方法,并比较了不同产地泽泻多糖中的单糖组成差异。经测定泽泻多糖中含有葡萄糖、半乳糖、半乳糖醛酸和阿拉伯糖,其中葡萄糖含量最高,说明泽泻多糖是以葡聚糖为主的杂多糖。不同产地泽泻多糖中葡萄糖、半乳糖、半乳糖醛酸含量差异显著(P<0.05),葡萄糖含量由高到低依次为广泽泻(166.940~264.724 mg/g)、川泽泻(82.647~155.019 mg/g)和建泽泻(51.148~97.746 mg/g);广泽泻多糖中半乳糖含量(3.511~3.840 mg/g)显著高于川泽泻(1.193~1.797 mg/g,P<0.01)和建泽泻(低于定量限);仅有广泽泻中半乳糖醛酸含量(1.342~1.823 mg/g)高于方法定量限。广泽泻中葡萄糖、半乳糖、半乳糖醛酸摩尔比为60.13∶1∶0.40,川泽泻中葡萄糖、半乳糖摩尔比为1545.05∶1,建泽泻多糖中几乎都是葡萄糖,葡萄糖占比在上述产地多糖中依次增加,三种单糖的杂合程度依次减弱。研究结果将为泽泻多糖的结构研究和质量控制奠定基础。

基于网络药理学及分子对接技术探讨泽泻治疗动脉粥样硬化作用机制

目的:利用网络药理学及分子对接技术探讨泽泻治疗动脉粥样硬化的作用机制。方法:通过中药系统药理学数据库与分析平台(TCMSP)、Swiss Target Prediction数据库筛选泽泻的活性成分及相关靶点。利用Gene Cards、OMIM、TTD等数据库检索动脉粥样硬化疾病相关靶点,最后得到泽泻与动脉粥样硬化的共同靶点,并进行GO生物进程及KEGG通路富集分析,应用AutoDock Vina软件进行分子对接验证。结果:泽泻的10个主要活性成分和327个潜在靶点,可能通过调节磷脂酰肌醇-3-激酶(PI3K)、白细胞介素(IL)、表皮生长因子等相关蛋白及PI3K-Akt、IL-17、AGE-RAGE等信号通路影响脂质代谢、类固醇代谢、炎症反应,分子对接验证结果提示泽泻醇B、泽泻醇C、泽泻醇A与核心靶点蛋白结合活性更显著。结论:泽泻通过调节脂质代谢、抗炎、抗氧化应激、调节内皮功能等反应发挥抗动脉粥样硬化的作用,为临床应用提供了药理依据。

基于网络药理学-分子对接技术探讨泽泻抗炎作用的分子机制

目的:应用网络药理学方法及分子对接技术,探讨泽泻发挥抗炎作用的活性成分及其对应靶点和相关通路。方法:通过TCMSP筛选出泽泻的活性成分,运用Swiss Target Prediction数据库预测活性成分相关靶标,同时采用GeneCards数据库得到炎症相关靶点,再将所得的活性成分靶点和炎症靶点导入VENNY2.1得到药物治疗疾病的潜在靶点;再运用STRING数据库、Cytoscape3.7.1软件构建简化后的药物治疗疾病的靶蛋白互作图(PPI)并筛选关键靶点;利用DAVID数据库对关键靶点进行GO功能富集分析和KEGG信号通路分析,再用Cytoscape3.7.1软件构建“化合物-靶点-通路”图并筛选核心成分与核心靶点;最后运用Auto Dock Vina和Pymol将核心成分与核心靶点进行分子对接。结果:获得10个药物活性成分,得到相关潜在靶点284个,疾病潜在靶点11414个,药物治疗疾病的相关靶点260个;有SRC、HSP90AA1、PIK3CA、MAPK1、AKT1、LCK、FYN、JAK1、PLCG1、JAK1等关键靶点58个;涉及PI3K-AKT信号通路、ErbB信号通路、FoxO信号通路等133条通路。结论:泽泻发挥抗炎的作用机制可能是一方面通过调控PIK3、AKT、m-TOR等相关蛋白,激活PI3K-AKT信号通路,从而抑制细胞凋亡;另一方面可能通过调控EGFR相关蛋白,介导ErbB信号通路,从而干预炎症细胞生长。本研究基于网络药理学方法和分子对接技术,阐释泽泻通过多种成分、多靶点、多信号通路发挥抗炎作用与机制,为该药的进一步研究提供有益参考和科学依据。

基于多元计量法的川泽泻药材商品等级评价标准研究

随着我国泽泻药材主流商品的重大变化,亟待建立川泽泻药材商品规格等级标准。本文将42批川泽泻药材商品初步划分为73组,量化测定其潜在分级指标,包括单个重、长度、直径、粉末色度值(L^(*)、a^(*)、b^(*))等外观性状指标,及浸出物、3种三萜类药效成分(23-乙酰泽泻醇B、23-乙酰泽泻醇C和泽泻醇B)、总三萜、总多糖的含量等内在物质基础指标。综合运用描述统计法、方差分析法、熵权法、灰色关联度法、相关性分析法对测定数据开展多元计量学分析,筛选出单个重、长度、3种三萜类成分总含量作为川泽泻药材商品的等级划分指标。以K-均值聚类分析法初步拟定川泽泻商品等级标准为:一等品单个重≥25 g,长度5.5~7.0 cm,3种三萜类成分总含量≥0.6%;二等品单个重15~25 g,长度4.0~5.5 cm,3种三萜类成分总含量0.4%~0.6%;统货单个重≥10 g,长度2.0~7.0 cm,3种三萜类成分总含量≥0.2%。综上所述,本研究筛选出川泽泻商品等级划分的科学指标,并拟订川泽泻药材商品等级标准(草案),有利于促进商品市场泽泻药材实现“优质优价”。

常见中药在治疗血脂异常中的研究新进展

血脂异常是由多种复杂原因导致的人体代谢性疾病,山楂、银杏叶、绞股蓝、泽泻、虎杖作为常见中药,在治疗血脂异常中具有一定的作用。本文总结了国内外最新研究进展,综述了常见中药山楂、银杏叶、绞股蓝、泽泻、虎杖等在治疗血脂异常中的作用,提示这些中药在防治血脂异常相关疾病如动脉粥样硬化中具有十分重要的意义。

气质联用检测不同提取方法对泽泻挥发性成分的影响研究

[目的]分析和比较不同提取方式下的泽泻挥发性成分,为研究泽泻挥发物的药理活性及完善泽泻药材质量评价提供依据。[方法]采用水蒸气蒸馏法与顶空进样法提取泽泻挥发物,利用气相色谱-质谱(GC-MS)分别对两种提取方式下的挥发性化学成分进行定性分析。[结果]水蒸气蒸馏法的泽泻挥发物中鉴定出56个化学成分,占挥发性成分总含量的36.89%,以倍半萜烯类、酮类、醛类化合物为主,主要为愈创木烯(5.98%)、γ-古芸烯(3.04%)、α-紫穗槐烯(2.94%)等;顶空进样法的泽泻挥发物中共鉴定出71个化学成分,占挥发性成分总含量的84.5%,以醛类、杂环类、萜烯类为主,主要为正己醛(38.39%)、2-戊基呋喃(6.91%)、α-紫穗槐烯(3.36%)等。[结论]两种方法提取得到的泽泻挥发油的化学成分种和相对含量均有所差异,综合利用两种方法可建立更全面的泽泻挥发性成分的GC-MS信息。

Correlation analysis between the chemical contents and bioactivity for the quality control of Alismatis Rhizoma

In order to clarify regions of production and to discriminate processing methods, quantitative and qualitative analyses for saccharides and terpenes in 35 batches of Alismatis Rhizoma were performed.Methodologies included HPLC–PDA, HPLC–VWD and UHPLC–MSn, combined with principal component analysis(PCA) and partial least squares regression techniques(PLSR). The inhibitory effects of triterpenes and Alismatis Rhizoma extracts on lipase activity were evaluated in vitro. PLSR analysis revealed significant positive correlations(R2= 0.5795) between the contents of triterpenes 10, 14, 15, 18 and 22 and the inhibitory effects of Alismatis Rhizoma. The present study establishes an effective method for simultaneous determination of multiple components, and identifies key bioactive triterpenes. These results can be used for systematic and novel analytical strategies for the quality control of Alismatis Rhizoma production.

Hypolipidemic effects of Alismatis Rhizoma decoction on the lipid profile in hyperlipidemia rats by RNA-sequencing

As a disorder of lipid metabolism,hyperlipidemia(HLP)is characterized by elevated levels of lipids in the blood circulation.It is consistently related to the development of cardiovascular events and diseases associated with metabolic syndrome.Alismatis Rhizoma decoction(ARD),a well-known traditional Chinese medicine prescription,has long been used for treating vertigo,which is a symptom experienced by HLP patients.In this study,we aimed to investigate the hyperlipidemic activity and the potential molecular mechanisms of ARD in HLP rats at the transcriptional level.RNA sequencing and transcriptome analysis were performed collaboratively,including analysis of differentially expressed genes(DEGs),GO functions,and KEGG pathway analysis.The results showed that 1981 DEGs(1370 upregulated and 611 downregulated)were identified in the HFD group compared with the CON group.Moreover,474 DEGs(350 upregulated and 124 downregulated)were detected in the ARD group compared with the HFD group.Furthermore,GO analysis revealed that DEGs were mainly involved in the following functions:developmental process,response to an external stimulus,ion transport,alcohol binding,and plasma membrane part.Pathway analysis suggested that these DEGs were significantly enriched in bile secretion,malaria,cell adhesion molecules,retinol metabolism,the sphingolipid signaling pathway,chemical carcinogenesis,and the T cell receptor signaling pathway.In conclusion,our study demonstrated that ARD alleviated the lipid metabolism disorder caused by HLP through multiple mechanisms,which provided vital scientific evidence for further pharmacological studies of ARD.

中药化学融入中医类专业的三维教学实践——以大黄为例

随着现代医药技术的迅速发展,人们对于疾病原因和药物作用机理认识日益深刻,单纯宏观思维模式已难以适应新时代下中医的教学与发展需求,亟须引入新的教学方法或模式。中医药防治疾病有赖于其药效物质基础——中药化学成分,本文在中医药理论指导下,以大黄为例,围绕蒽醌类化学成分,将化学引入中医的教学实践。通过理论、实践及拓展这三个维度的课堂教学,有效提升了学生对中医药的认知和应用能力,为中医复合型人才培养提供了参考。