TongMai Granules is a Chinese medicine patent drug to treat cardiovascular diseases.It is prepared from the water extract of Dan-shen,Chuan-xiong and Ge-gen.The main compounds of TongMai Granules are isoflavone glycos...TongMai Granules is a Chinese medicine patent drug to treat cardiovascular diseases.It is prepared from the water extract of Dan-shen,Chuan-xiong and Ge-gen.The main compounds of TongMai Granules are isoflavone glycosides,isoflavones,and phenolic acids.However,it is difficult to detect low-polar compounds such as tanshinones and phthalides though they may also contribute to the therapeutic effect.In this work,an off-line two-dimensional chromatography method was developed to enrich the minor constituents in TongMai Granules.The extract was subjected to an SEP-PAK silica SPE column and eluted with petroleum ether,ethyl acetate–methanol(6:1,v/v),and methanol,successively.The three fractions were then analyzed using ultra-high performance liquid chromatography coupled with orbitrap mass spectrometry(UHPLC/orbitrap-MS).The isoflavones from Ge-gen,phenolic acids from Dan-shen and phthalides from Chuan-xiong were distributed in different fractions.A total of 131 compounds,including 59 from Ge-gen,26 from Dan-shen,43 from Chuan-xiong,and 3 common ones from Dan-shen and Chuan-xiong were tentatively identified.Among them,26 compounds were identified by comparing with reference standards.This study set a good example for comprehensive analysis of the constituents in traditional Chinese medicine formula.展开更多
Ziziphi Spinosae Semen(ZSS),a traditional Chinese medicine,is used in clinics for the treatment of insomnia in China and other Asian countries.Herein,we described for the first time a comparative pharmacokinetics stud...Ziziphi Spinosae Semen(ZSS),a traditional Chinese medicine,is used in clinics for the treatment of insomnia in China and other Asian countries.Herein,we described for the first time a comparative pharmacokinetics study of the six major compounds of ZSS in normal control(NC)and para-chlorophenylalanine(PCPA)-induced insomnia model(IM)rats that were orally administered the aqueous extract of ZSS.An ultra-high-performance liquid chromatography coupled with quadrupole orbitrap mass(UHPLC-Q-Orbitrap-MS)method was developed and validated for the simultaneous determination of coclaurine,magnoflorine,spinosin,6000-feruloylspinosin,jujuboside A(JuA),and jujuboside B(JuB)in ZSS in rat plasma.The established approach was successfully applied to a comparative pharmacokinetic study.The systemic exposures of spinosin and 6000-feruloylspinosin were decreased in the IM group compared to the NC group,while plasma clearance(CL)was significantly increased.The Tmax values of JuA and JuB in IM rats were significantly lower than those in NC rats.The T1/2 of JuA in the IM group was significantly accelerated.The pharmacokinetic parameters of coclaurine and magnoflorine were not evidently affected between the two groups.These results indicate that the pathological state of insomnia altered the plasma pharmacokinetics of spinosin,6000-feruloylspinosin,JuA,and JuB in the ZSS aqueous extract,providing an experimental basis for the role of ZSS in insomnia treatment.The comparative pharmacokinetics-based UHPLC-Q-Orbitrap-MS using full-scan mode can therefore provide a reliable and suitable means for the screening of potentially effective substances applied as quality markers of ZSS.展开更多
目的基于多元统计分析和网络药理学分析预测炒酸枣仁饮片潜在的质量标志物(Q-Marker)。方法利用超高效液相色谱-四极杆-静电场轨道阱质谱联用(ultra performance liquid chromatography-quadrupole-electrostatic field orbital trap ma...目的基于多元统计分析和网络药理学分析预测炒酸枣仁饮片潜在的质量标志物(Q-Marker)。方法利用超高效液相色谱-四极杆-静电场轨道阱质谱联用(ultra performance liquid chromatography-quadrupole-electrostatic field orbital trap mass spectrometry,UHPLC-Q-Orbitrap-MS)解析生、炒酸枣仁饮片的主要成分,运用多元统计分析结合VIP>1和P<0.05筛选出炮制前后潜在的差异化学成分。结合网络药理学筛选核心靶点构建"成分-靶点-通路"网络关系,预测炒酸枣仁潜在的Q-Marker,以潜在Q-Marker为指标对市售样品进行含量测定,验证Q-Marker的科学性。结果生、炒酸枣仁共鉴定54个化学成分,包括斯皮诺素、当药黄素等黄酮类成分,酸枣仁皂苷A、酸枣仁皂苷B等皂苷类成分,以及木兰花碱、乌药碱等生物碱类成分;结合多元统计分析共找到木兰花碱、6"’-阿魏酰斯皮诺素、酸枣仁皂苷A、白桦脂酸等28个差异性成分;经网络药理学分析筛选出包括17个差异成分的Q-Marker库,分别为酸枣仁皂苷A、酸枣仁皂苷B、美洲茶酸、白桦脂酸、木兰花碱、乌药碱、去甲荷叶碱、巴婆碱、斯皮诺素、当药黄素、维采宁Ⅱ、6"’-对-香豆酰斯皮诺素、6"’-阿魏酰斯皮诺素、芹菜素、桦木酮酸、牡荆素、异牡荆素;结合课题组前期研究及市售样品测定结果,最终确定木兰花碱、乌药碱、斯皮诺素、6"’-阿魏酰斯皮诺素、酸枣仁皂苷A和B作为炒酸枣仁的Q-Marker。结论分析预测的Q-Marker为炒酸枣仁的整体质量控制及临床应用提供科学依据,同时也为其功效关联物质的研究及作用机制的阐释奠定基础。展开更多
目的探究黄芪的3个重要产地(山西浑源与朔州、甘肃渭源与岷县、陕西子洲)所产黄芪饮片的成分差异,为其基原鉴定与质量研究提供参考依据。方法用超高效液相色谱-四级杆/静电场轨道阱高分辨质谱技术(UHPLC-Q-Orbitrap-MS)测定3个不同产地...目的探究黄芪的3个重要产地(山西浑源与朔州、甘肃渭源与岷县、陕西子洲)所产黄芪饮片的成分差异,为其基原鉴定与质量研究提供参考依据。方法用超高效液相色谱-四级杆/静电场轨道阱高分辨质谱技术(UHPLC-Q-Orbitrap-MS)测定3个不同产地黄芪饮片的化学成分。以变量投影重要性(VIP)>1、P<0.05为标准,筛选获得其显著差异成分,用SIMCA软件对所得化合物及差异化合物进行聚类分析、偏最小二乘法判别分析(partial least squares discriminant analysis,PLS-DA)。结果4-羟基肉桂酸、胱氨酸、刺芒柄花素等21个化合物在甘肃、陕西、山西3个产地黄芪之间存在显著差异,其中甘肃与山西产地的黄芪差异性成分有1个,山西与陕西产地的黄芪差异成分有11个,甘肃与陕西产地的黄芪差异成分有18个。结论基于UHPLC-QOrbitrap-MS液质联用技术及聚类分析、PLS-DA等成分分析方法所得21个差异性成分,可为不同产地及品种黄芪饮片的来源鉴定及质量控制提供理论依据。展开更多
目的:探讨茵栀黄颗粒主要化学成分及其药理作用机制。方法:色谱柱选用Waters公司ACQUITY PRM UPLC BEH C;Column with Van Guard FIT色谱柱(2.1 mm×100 mm, 1.7μm),梯度洗脱的流动相为0.1%甲酸溶液-乙腈;采用高分辨液质联用质谱(U...目的:探讨茵栀黄颗粒主要化学成分及其药理作用机制。方法:色谱柱选用Waters公司ACQUITY PRM UPLC BEH C;Column with Van Guard FIT色谱柱(2.1 mm×100 mm, 1.7μm),梯度洗脱的流动相为0.1%甲酸溶液-乙腈;采用高分辨液质联用质谱(UHPLC-LTQ-Orbitrap-MS)正负离子扫描模式。并利用中药系统药理学数据库与分析平台和Swiss Target Prediction数据库对检测得到的化合物成分进行靶点预测,结合Cytoscape 3.8.2绘制关联网络图,对核心靶基因进行基因本体功能富集分析和京都基因与基因组百科全书通路富集分析,构建成分-靶点-通路网络图。利用Autodock vina软件对疾病靶点和茵栀黄颗粒的主要化学成分进行分子对接验证。结果:依据从精确相对分子质量数据和多级质谱碎片离子数据获得的结果,结合对照品比对以及文献报道,共从茵栀黄颗粒中分析鉴定了68个化学成分,其中有14个化合物经对照品比对完全确定,主要包括苯丙素类化合物如绿原酸,香豆素类化合物如滨蒿内酯,黄酮类化合物如黄芩素、黄芩苷。网络药理学分析得到31个茵栀黄颗粒治疗黄疸的主要靶点,经过度值筛选得到排序居前5位的主要靶点及重要的相关信号通路。推断茵栀黄颗粒可能通过脂质与动脉粥样硬化方式,影响类固醇激素生物合成,从而治疗黄疸的前期病变等。结论:本研究初探了茵栀黄颗粒的主要化学成分及相关药理作用机制,为茵栀黄颗粒的进一步深入研究提供了参考。展开更多
基金National Key Research and Development Program of China(Grant No.2018YFC1707301,2018YFC1707304)。
文摘TongMai Granules is a Chinese medicine patent drug to treat cardiovascular diseases.It is prepared from the water extract of Dan-shen,Chuan-xiong and Ge-gen.The main compounds of TongMai Granules are isoflavone glycosides,isoflavones,and phenolic acids.However,it is difficult to detect low-polar compounds such as tanshinones and phthalides though they may also contribute to the therapeutic effect.In this work,an off-line two-dimensional chromatography method was developed to enrich the minor constituents in TongMai Granules.The extract was subjected to an SEP-PAK silica SPE column and eluted with petroleum ether,ethyl acetate–methanol(6:1,v/v),and methanol,successively.The three fractions were then analyzed using ultra-high performance liquid chromatography coupled with orbitrap mass spectrometry(UHPLC/orbitrap-MS).The isoflavones from Ge-gen,phenolic acids from Dan-shen and phthalides from Chuan-xiong were distributed in different fractions.A total of 131 compounds,including 59 from Ge-gen,26 from Dan-shen,43 from Chuan-xiong,and 3 common ones from Dan-shen and Chuan-xiong were tentatively identified.Among them,26 compounds were identified by comparing with reference standards.This study set a good example for comprehensive analysis of the constituents in traditional Chinese medicine formula.
基金This work was supported by grants from the National Natural Science Foundation of China(No:81603289,81603251)Key Laboratory of Effective Substances Research and Utilization in TCM of Shanxi province(No:201605D111004)and Key Technology Research Zhen Dong Special Project from Shanxi Science and Technology Department(No:2016ZD0105).
文摘Ziziphi Spinosae Semen(ZSS),a traditional Chinese medicine,is used in clinics for the treatment of insomnia in China and other Asian countries.Herein,we described for the first time a comparative pharmacokinetics study of the six major compounds of ZSS in normal control(NC)and para-chlorophenylalanine(PCPA)-induced insomnia model(IM)rats that were orally administered the aqueous extract of ZSS.An ultra-high-performance liquid chromatography coupled with quadrupole orbitrap mass(UHPLC-Q-Orbitrap-MS)method was developed and validated for the simultaneous determination of coclaurine,magnoflorine,spinosin,6000-feruloylspinosin,jujuboside A(JuA),and jujuboside B(JuB)in ZSS in rat plasma.The established approach was successfully applied to a comparative pharmacokinetic study.The systemic exposures of spinosin and 6000-feruloylspinosin were decreased in the IM group compared to the NC group,while plasma clearance(CL)was significantly increased.The Tmax values of JuA and JuB in IM rats were significantly lower than those in NC rats.The T1/2 of JuA in the IM group was significantly accelerated.The pharmacokinetic parameters of coclaurine and magnoflorine were not evidently affected between the two groups.These results indicate that the pathological state of insomnia altered the plasma pharmacokinetics of spinosin,6000-feruloylspinosin,JuA,and JuB in the ZSS aqueous extract,providing an experimental basis for the role of ZSS in insomnia treatment.The comparative pharmacokinetics-based UHPLC-Q-Orbitrap-MS using full-scan mode can therefore provide a reliable and suitable means for the screening of potentially effective substances applied as quality markers of ZSS.
文摘目的基于多元统计分析和网络药理学分析预测炒酸枣仁饮片潜在的质量标志物(Q-Marker)。方法利用超高效液相色谱-四极杆-静电场轨道阱质谱联用(ultra performance liquid chromatography-quadrupole-electrostatic field orbital trap mass spectrometry,UHPLC-Q-Orbitrap-MS)解析生、炒酸枣仁饮片的主要成分,运用多元统计分析结合VIP>1和P<0.05筛选出炮制前后潜在的差异化学成分。结合网络药理学筛选核心靶点构建"成分-靶点-通路"网络关系,预测炒酸枣仁潜在的Q-Marker,以潜在Q-Marker为指标对市售样品进行含量测定,验证Q-Marker的科学性。结果生、炒酸枣仁共鉴定54个化学成分,包括斯皮诺素、当药黄素等黄酮类成分,酸枣仁皂苷A、酸枣仁皂苷B等皂苷类成分,以及木兰花碱、乌药碱等生物碱类成分;结合多元统计分析共找到木兰花碱、6"’-阿魏酰斯皮诺素、酸枣仁皂苷A、白桦脂酸等28个差异性成分;经网络药理学分析筛选出包括17个差异成分的Q-Marker库,分别为酸枣仁皂苷A、酸枣仁皂苷B、美洲茶酸、白桦脂酸、木兰花碱、乌药碱、去甲荷叶碱、巴婆碱、斯皮诺素、当药黄素、维采宁Ⅱ、6"’-对-香豆酰斯皮诺素、6"’-阿魏酰斯皮诺素、芹菜素、桦木酮酸、牡荆素、异牡荆素;结合课题组前期研究及市售样品测定结果,最终确定木兰花碱、乌药碱、斯皮诺素、6"’-阿魏酰斯皮诺素、酸枣仁皂苷A和B作为炒酸枣仁的Q-Marker。结论分析预测的Q-Marker为炒酸枣仁的整体质量控制及临床应用提供科学依据,同时也为其功效关联物质的研究及作用机制的阐释奠定基础。
文摘目的探究黄芪的3个重要产地(山西浑源与朔州、甘肃渭源与岷县、陕西子洲)所产黄芪饮片的成分差异,为其基原鉴定与质量研究提供参考依据。方法用超高效液相色谱-四级杆/静电场轨道阱高分辨质谱技术(UHPLC-Q-Orbitrap-MS)测定3个不同产地黄芪饮片的化学成分。以变量投影重要性(VIP)>1、P<0.05为标准,筛选获得其显著差异成分,用SIMCA软件对所得化合物及差异化合物进行聚类分析、偏最小二乘法判别分析(partial least squares discriminant analysis,PLS-DA)。结果4-羟基肉桂酸、胱氨酸、刺芒柄花素等21个化合物在甘肃、陕西、山西3个产地黄芪之间存在显著差异,其中甘肃与山西产地的黄芪差异性成分有1个,山西与陕西产地的黄芪差异成分有11个,甘肃与陕西产地的黄芪差异成分有18个。结论基于UHPLC-QOrbitrap-MS液质联用技术及聚类分析、PLS-DA等成分分析方法所得21个差异性成分,可为不同产地及品种黄芪饮片的来源鉴定及质量控制提供理论依据。
