Objective:The aim of the present study was to determine the quality marker(Q-Markers)of Sparganii Rhizoma against thrombus through an integration of investigations on its antithrombotic effect,content determination an...Objective:The aim of the present study was to determine the quality marker(Q-Markers)of Sparganii Rhizoma against thrombus through an integration of investigations on its antithrombotic effect,content determination and spectrum-effect correlation analysis.Methods:Based on the concept of Q-Marker,Sparganii Rhizoma was investigated for the identification of chemical component.The pharmacological effects on arachidonic acid-induced thrombosis in zebrafish were also investigated.The material basis in ethanol extract was determined by HPLC-UV.Furthermore,the potential Q-Markers were analyzed and predicted according to the effect-chemical correlation analysis.Finally,the anti-thrombotic Q-Markers were verified through the anti-thrombotic test of monomer components.Results:The model of thrombosis zebrafish was established with larvae exposed to 100 mmol/L arachidonic acid for 1 h.Nine ingredients in Sparganii Rhizoma were identified as 5-hydroxymethylfurfural,vanillic acid,ferulic acid,p-hydroxybenzaldehyde,p-hydroxybenzoic acid,vanillin,protocatechuic acid,p-coumaric acid and isoferulic acid.According to the determination effect of zebrafish thrombosis model and HPLC content analysis results,all the other contents present positive correlation except 5-hydroxymethylfurfural,and the P values of three representative potential Q-Markers(ferulic acid,protocatechuic acid and p-coumaric acid)were 0.002,0.001 and 0.026,respectively.Conclusion:Sparganii Rhizoma showed a dose-dependent effect on the recovery of reducing cardiac red blood cell on zebrafish model.Three phenolic acids(ferulic acid,protocatechuic acid and p-coumaric acid)were proved to possess the anti-thrombotic effects which could be regarded as the potential QMarkers for quality assessment of Sparganii Rhizoma.展开更多
[目的]探讨活血祛瘀药对“三棱-莪术”治疗胃癌(gastric cancer,GC)的有效活性成分及作用机制。[方法]通过中药系统药理学数据库与分析平台(Tradrtional Chinese Medicine systems Pharmacology Database and Analysis Platform,TCMSP)...[目的]探讨活血祛瘀药对“三棱-莪术”治疗胃癌(gastric cancer,GC)的有效活性成分及作用机制。[方法]通过中药系统药理学数据库与分析平台(Tradrtional Chinese Medicine systems Pharmacology Database and Analysis Platform,TCMSP)选取三棱-莪术药对中含有的111个化合物,筛选其活性成分及潜在靶点;通过人类孟德尔遗传数据库、Gene Cards数据库挖掘GC疾病靶点;结合化合物及疾病靶点,构建化合物-靶点网络图,并进行基因本体(gene ontology,GO)功能富集及京都基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)通路富集分析。[结果]“三棱-莪术”药对中含有60个活性成分,对应GC 67个靶点;主要调控GC细胞的生长增殖周期,包括对细胞核、细胞质、DNA转录、RNA聚合酶Ⅱ启动子等的作用,及对类固醇激素受体活性、丝氨酸型内肽酶活性的调控;发挥作用的重要靶点为半胱天冬氨酸蛋白酶-3(caspase-3,CASP3)、c-Jun N-末端激酶(c-Jun N-terminal kinase,JNK)、雌激素受体1(estrogen receptor 1,ESR1)、热休克蛋白90AA1(heat shock protein90AA1,HSP90AA1)、前列素内环氧化物合成酶2(prostaglandin endoperoxide synthase 2,PTGS2);主要作用的信号通路有肿瘤信号通路、磷脂酰肌醇3-激酶-蛋白激酶B(phosphatidylinositol 3-kinases-protein kinase B/Akt,PI3K-PKB/Akt)信号通路、p53信号通路、血管内皮生长因子(vascular endothelial growth factor,VEGF)信号通路、肿瘤坏死因子(tumor necrosis factor,TNF)信号通路、钙信号通路、鞘脂类信号通路等。[结论]中医活血祛瘀之代表“三棱-莪术”药对治疗胃癌作用机制确切,主要通过对细胞周期、靶点蛋白及信号通路的调控发挥其治疗作用。展开更多
基金supported by the Shandong Provincial Chinese Medicine Science and Technology Development Project(2017165)Shandong Provincial Natural Science Fund Project(ZR2015HL117)。
文摘Objective:The aim of the present study was to determine the quality marker(Q-Markers)of Sparganii Rhizoma against thrombus through an integration of investigations on its antithrombotic effect,content determination and spectrum-effect correlation analysis.Methods:Based on the concept of Q-Marker,Sparganii Rhizoma was investigated for the identification of chemical component.The pharmacological effects on arachidonic acid-induced thrombosis in zebrafish were also investigated.The material basis in ethanol extract was determined by HPLC-UV.Furthermore,the potential Q-Markers were analyzed and predicted according to the effect-chemical correlation analysis.Finally,the anti-thrombotic Q-Markers were verified through the anti-thrombotic test of monomer components.Results:The model of thrombosis zebrafish was established with larvae exposed to 100 mmol/L arachidonic acid for 1 h.Nine ingredients in Sparganii Rhizoma were identified as 5-hydroxymethylfurfural,vanillic acid,ferulic acid,p-hydroxybenzaldehyde,p-hydroxybenzoic acid,vanillin,protocatechuic acid,p-coumaric acid and isoferulic acid.According to the determination effect of zebrafish thrombosis model and HPLC content analysis results,all the other contents present positive correlation except 5-hydroxymethylfurfural,and the P values of three representative potential Q-Markers(ferulic acid,protocatechuic acid and p-coumaric acid)were 0.002,0.001 and 0.026,respectively.Conclusion:Sparganii Rhizoma showed a dose-dependent effect on the recovery of reducing cardiac red blood cell on zebrafish model.Three phenolic acids(ferulic acid,protocatechuic acid and p-coumaric acid)were proved to possess the anti-thrombotic effects which could be regarded as the potential QMarkers for quality assessment of Sparganii Rhizoma.
