基于网络药理学的浙产栀子藏红花素类成分药理作用机制研究
|
摘要
目的运用网络药理学方法研究浙江产区栀子藏红花素类成分药理作用机制,为浙产栀子药材的合理使用与深度研发提供有价值的研究策略。方法课题组前期研究成果显示,浙江产区栀子中藏红花素类成分含量与其他产地比较有显著性差异,依据该结果,本研究联合使用Pubchem、Uniprot、STITCH、SWISS、TCMSP多个在线靶点筛选与预测数据库,运用Cytoscape软件构建化学成分-靶点-疾病(component-target-disease,C-T-D)相关作用网络模型。对浙产栀子特征性高含量化学成分群藏红花素类化合物相关靶点进行挖掘预测,借助CTD数据库对靶点进行基因本体(gene ontology,GO)富集与KEGG通路分析,进一步挖掘浙产栀子多维药理作用机制。结果浙产栀子中藏红花素类化合物藏红花素-二-β-D-龙胆二糖苷(crocin-1)、藏红花素-二-β-D-龙胆二糖-β-D-葡萄糖苷(crocin-2)通过成纤维细胞生长因子2(FGF2)、血管内皮生长因子A(VEGFA)、酪氨酸激酶受体(KDR)、血管内皮生长因子受体1(FLT1)等18个靶点作用于G蛋白偶联受体(GPCR)、Rap1、RAS等信号通路,从而参与细胞信号转导过程发挥多维药理作用,这些成分主要可治疗心血管疾病、肿瘤、消化系统等18种相关疾病。结论基于系统药理学的研究方法寻找不同产区药材特征性高含量化学成分群的关键靶点、信号通路和疾病网络,为深入研究我国不同产区中药资源的药理作用及机制提供信息和数据支撑。
Objective To investigate the pharmacological mechanism of the crocin compounds from Gardenia jasminoides in Zhejiang Province by using network pharmacology. To provide a valuable research strategy for the rational use and in-depth research and development of G. jasminoides from Zhejiang. Methods Our previous research results showed that the Zhejiang area of Gardenia crocin content and other areas have significant difference. Based on the results, the crocin compounds from G. jasminoides were used to predict the targets according to Pubchem, Uniprot, STITCH, SWISS, and TCMSP online databases. Cytoscape software was used to construct compound-target-disease network of the G. jasminoides crocin ingredients. The targets were analyzed by Gene ontology(GO) enrichment and KEGG pathway analysis using CTD online analysis platform to analyze main biological pathways for obtaining the deep mechanism of G. jasminoides in Zhejiang. Results The crocin compounds from G. jasminoides in Zhejiang Province were obtained through previous work and network pharmacology screening, such as crocin-1 and crocin-2, and 18 corresponding targets were acted, such as FGF2, VEGFA, KDR, and FLT1. These targets could joint in pathways, such as GPCR, Rap1, and Ras signaling pathway. These ingredients are mainly used to treat 18 related diseases such as cardiovascular diseases, tumors and digestive system. Conclusion The method based on system pharmacology could help to find the key targets of characteristic high-content chemical constituents of herb from different producing areas, signaling pathway and disease network of traditional Chinese medicine(TCM), and provide useful information and data support for giving a further study on TCM resources in different regions of China.
Objective To investigate the pharmacological mechanism of the crocin compounds from Gardenia jasminoides in Zhejiang Province by using network pharmacology. To provide a valuable research strategy for the rational use and in-depth research and development of G. jasminoides from Zhejiang. Methods Our previous research results showed that the Zhejiang area of Gardenia crocin content and other areas have significant difference. Based on the results, the crocin compounds from G. jasminoides were used to predict the targets according to Pubchem, Uniprot, STITCH, SWISS, and TCMSP online databases. Cytoscape software was used to construct compound-target-disease network of the G. jasminoides crocin ingredients. The targets were analyzed by Gene ontology(GO) enrichment and KEGG pathway analysis using CTD online analysis platform to analyze main biological pathways for obtaining the deep mechanism of G. jasminoides in Zhejiang. Results The crocin compounds from G. jasminoides in Zhejiang Province were obtained through previous work and network pharmacology screening, such as crocin-1 and crocin-2, and 18 corresponding targets were acted, such as FGF2, VEGFA, KDR, and FLT1. These targets could joint in pathways, such as GPCR, Rap1, and Ras signaling pathway. These ingredients are mainly used to treat 18 related diseases such as cardiovascular diseases, tumors and digestive system. Conclusion The method based on system pharmacology could help to find the key targets of characteristic high-content chemical constituents of herb from different producing areas, signaling pathway and disease network of traditional Chinese medicine(TCM), and provide useful information and data support for giving a further study on TCM resources in different regions of China.
引文
[1]邹立君.栀子黄色素的提取及抗氧化性研究[D].武汉:湖北工业大学,2017.
[2]Yorgun M A,Rahid K,Aslanids A,et al.Crocin,aplant-derived carotenoid,modulates microglial reactivity[J].Biochem Biophys Rep,2017,doi:10.1016/j.bbrep.2017.09.007.
[3]Chen Y,Zhang H,Li Y X,et al.Crocin and geniposide profiles and radical scavenging activity of gardenia fruits(Gardenia jasminoides Ellis)from different cultivars and at the various stages of maturation[J].Fitoterapia,2010,doi:10.1016/j.fitote.2009.09.011.
[4]于洋,高昊,戴毅,等.栀子属植物化学成分的研究进展[J].中草药,2010,41(1):148-153.
[5]中国科学院中国植物志编辑委员会.中国植物志[M].北京:科学出版社,1999.
[6]付小梅,赖学文,葛菲,等.中药栀子类药材资源调查和商品药材鉴定[J].中国野生植物资源,2002,21(5):23-25.
[7]吴亚超,刘佩文,李德坤,等.不同产地栀子的UPLC指纹图谱[J].中国实验方剂学杂志,2018,24(2):74-78.
[8]刘方舟,杨阳,张一颖,等.栀子药材道地性系统评价与分析[J].中国现代中药,2018,20(11):1330-1339.
[9]虞希冲,杨伟,吴波拉,等.网络药理学技术预测延胡索抗糖尿病作用及初步验证研究[J].中国药学杂志,2014,49(11):913-918.
[10]黄林芳,陈士林.中药品质生态学:一个新兴交叉学科[J].中国实验方剂学杂志,2017,23(1):1-11.
[11]梁飞,李健,张卫,等.谈“道地药材”的形成原因[J].中国中药杂志,2013,38(3):466-468.
[12]徐妍,杨华蕊,杨永寿,等.中药指纹图谱研究现状及展望[J].世界最新医学信息文摘,2018,18(76):91-94.
[13]顾静航.面向生物医学领域的实体关系抽取研究[D].苏州:苏州大学,2017.
[14]Raaijmakers J H,Bos J L.Specificity in Ras and Rap signaling[J].J Biol Chem,2009,284(17):10995-1099.
[2]Yorgun M A,Rahid K,Aslanids A,et al.Crocin,aplant-derived carotenoid,modulates microglial reactivity[J].Biochem Biophys Rep,2017,doi:10.1016/j.bbrep.2017.09.007.
[3]Chen Y,Zhang H,Li Y X,et al.Crocin and geniposide profiles and radical scavenging activity of gardenia fruits(Gardenia jasminoides Ellis)from different cultivars and at the various stages of maturation[J].Fitoterapia,2010,doi:10.1016/j.fitote.2009.09.011.
[4]于洋,高昊,戴毅,等.栀子属植物化学成分的研究进展[J].中草药,2010,41(1):148-153.
[5]中国科学院中国植物志编辑委员会.中国植物志[M].北京:科学出版社,1999.
[6]付小梅,赖学文,葛菲,等.中药栀子类药材资源调查和商品药材鉴定[J].中国野生植物资源,2002,21(5):23-25.
[7]吴亚超,刘佩文,李德坤,等.不同产地栀子的UPLC指纹图谱[J].中国实验方剂学杂志,2018,24(2):74-78.
[8]刘方舟,杨阳,张一颖,等.栀子药材道地性系统评价与分析[J].中国现代中药,2018,20(11):1330-1339.
[9]虞希冲,杨伟,吴波拉,等.网络药理学技术预测延胡索抗糖尿病作用及初步验证研究[J].中国药学杂志,2014,49(11):913-918.
[10]黄林芳,陈士林.中药品质生态学:一个新兴交叉学科[J].中国实验方剂学杂志,2017,23(1):1-11.
[11]梁飞,李健,张卫,等.谈“道地药材”的形成原因[J].中国中药杂志,2013,38(3):466-468.
[12]徐妍,杨华蕊,杨永寿,等.中药指纹图谱研究现状及展望[J].世界最新医学信息文摘,2018,18(76):91-94.
[13]顾静航.面向生物医学领域的实体关系抽取研究[D].苏州:苏州大学,2017.
[14]Raaijmakers J H,Bos J L.Specificity in Ras and Rap signaling[J].J Biol Chem,2009,284(17):10995-1099.