采用网络药理学方法及分子对接技术探析良附丸治疗功能性消化不良(functional dyspepsia, FD)潜在的作用机制,并通过动物实验研究良附丸对FD大鼠的干预作用及机制。利用TCMSP数据库(Traditional Chinese Medicine Systems Pharmacology ...采用网络药理学方法及分子对接技术探析良附丸治疗功能性消化不良(functional dyspepsia, FD)潜在的作用机制,并通过动物实验研究良附丸对FD大鼠的干预作用及机制。利用TCMSP数据库(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform)获取和筛选良附丸的活性成分,利用SwissTargetPrediction数据库预测药物的作用靶点,通过GeneCards数据库检索FD相关靶点;药物与疾病靶点相交集后,导入STRING数据库检索蛋白互作关系,筛选关键靶点,利用DAVID数据库进行GO(Gene Oncology)生物过程分析和KEGG(Kyoto Encyclopedia of Genes and Genomes)通路富集分析,最后借助AutoDock Tools软件进行分子对接,预测良附丸有效成分与关键靶点的结合度。网络药理学筛选出良附丸的活性成分19个及与FD相关的靶点591个,其中交集靶点253个;GO和KEGG富集分析发现良附丸主要与药物反应、转录的负调控、细胞凋亡的正调控、细胞表面受体信号通路等生物过程有关,富集在HIF-1信号通路、5-羟色胺能突触、TNF信号通路、cAMP信号通路、钙信号通路、TRP通道的炎症介质调节等。分子对接结果显示良附丸关键有效成分与靶点MAPK1、AKT1、TRPV1、HTR1A、HTR2A均有一定的结合活性。动物实验构建FD大鼠模型,造模成功后给予良附丸治疗7 d,检测结果显示,良附丸组能显著缓解FD大鼠的症状,且明显升高5-HT的表达水平,下调TRPV1的表达。通过网络药理学、分子对接分析和实验验证,证明良附丸对功能性消化不良的改善具有多成分、多靶点的特点,为进一步的良附丸治疗功能性消化不良机制研究及临床应用提供了依据。展开更多
In the present study, two new compounds from Ipomoea cairica were identified and demonstrated to have a-glucosidase inhibitory activity. They were isolated by column chromatography on silica gel and sephadex LH-20 and...In the present study, two new compounds from Ipomoea cairica were identified and demonstrated to have a-glucosidase inhibitory activity. They were isolated by column chromatography on silica gel and sephadex LH-20 and finally purified by prep-HPLC, with their structures being elucidated by spectroscopic methods, such as 1D- and 2D-NMR and HR-TOF-MS, and chemical methods. Compounds 1 and 2, named cairicoside A and cairicoside B, were evaluated for a-glucosidase inhibitory activity by the MTT method, with the ICs0 values being 25.3 ± 1.6 and 28.5± 3.3 μmol·L-1, respectively.展开更多
In the present study, three compounds were isolated from Argyreia acuta, among them, compounds 1 and 2 were new and Compounds 1 and 3 were isomers. They were separated by several types of columns, such as normal phase...In the present study, three compounds were isolated from Argyreia acuta, among them, compounds 1 and 2 were new and Compounds 1 and 3 were isomers. They were separated by several types of columns, such as normal phase, RP, size exclusion and preparative HPLC, and their structures were elucidated by several spectroscopic methods, such as 1D-and 2D-NMR and HR-TOF-MS.展开更多
文摘采用网络药理学方法及分子对接技术探析良附丸治疗功能性消化不良(functional dyspepsia, FD)潜在的作用机制,并通过动物实验研究良附丸对FD大鼠的干预作用及机制。利用TCMSP数据库(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform)获取和筛选良附丸的活性成分,利用SwissTargetPrediction数据库预测药物的作用靶点,通过GeneCards数据库检索FD相关靶点;药物与疾病靶点相交集后,导入STRING数据库检索蛋白互作关系,筛选关键靶点,利用DAVID数据库进行GO(Gene Oncology)生物过程分析和KEGG(Kyoto Encyclopedia of Genes and Genomes)通路富集分析,最后借助AutoDock Tools软件进行分子对接,预测良附丸有效成分与关键靶点的结合度。网络药理学筛选出良附丸的活性成分19个及与FD相关的靶点591个,其中交集靶点253个;GO和KEGG富集分析发现良附丸主要与药物反应、转录的负调控、细胞凋亡的正调控、细胞表面受体信号通路等生物过程有关,富集在HIF-1信号通路、5-羟色胺能突触、TNF信号通路、cAMP信号通路、钙信号通路、TRP通道的炎症介质调节等。分子对接结果显示良附丸关键有效成分与靶点MAPK1、AKT1、TRPV1、HTR1A、HTR2A均有一定的结合活性。动物实验构建FD大鼠模型,造模成功后给予良附丸治疗7 d,检测结果显示,良附丸组能显著缓解FD大鼠的症状,且明显升高5-HT的表达水平,下调TRPV1的表达。通过网络药理学、分子对接分析和实验验证,证明良附丸对功能性消化不良的改善具有多成分、多靶点的特点,为进一步的良附丸治疗功能性消化不良机制研究及临床应用提供了依据。
基金supported by Chinese National Natural Science Fund(No.81202885)the Natural Science Foundation of Guangdong province of China(No.2015A030313585)
文摘In the present study, two new compounds from Ipomoea cairica were identified and demonstrated to have a-glucosidase inhibitory activity. They were isolated by column chromatography on silica gel and sephadex LH-20 and finally purified by prep-HPLC, with their structures being elucidated by spectroscopic methods, such as 1D- and 2D-NMR and HR-TOF-MS, and chemical methods. Compounds 1 and 2, named cairicoside A and cairicoside B, were evaluated for a-glucosidase inhibitory activity by the MTT method, with the ICs0 values being 25.3 ± 1.6 and 28.5± 3.3 μmol·L-1, respectively.
基金supported by National Natural Science Fundation of China(Nos.81202885,81373931,81573877,and 81403074)the Natural Science Foundation of Guangdong Province of China(No.2015A030313585)
文摘In the present study, three compounds were isolated from Argyreia acuta, among them, compounds 1 and 2 were new and Compounds 1 and 3 were isomers. They were separated by several types of columns, such as normal phase, RP, size exclusion and preparative HPLC, and their structures were elucidated by several spectroscopic methods, such as 1D-and 2D-NMR and HR-TOF-MS.