基于网络药理学研究钩藤治疗高血压的作用机制
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摘要
目的基于网络药理学方法研究钩藤治疗高血压的作用机制。方法利用TCMSP数据库筛选钩藤中口服生物利用度(OB)≥30%和类药性(DL)≥0.18的化学成分作为潜在药效成分,在TCMSP数据库中检索成分作用靶点。结合GeneCards、TTD、OMIM数据库检索高血压疾病相关靶点,提取成分和高血压疾病的共有靶点作为关键靶点。利用CluGO插件对关键靶点进行GO功能富集分析和KEGG通路富集分析,构建"成分-靶点-信号通路"网络。结果筛选得到11种潜在的药效成分,协同作用于PTGS1、PTGS12、CHRM1、ADRα1B等关键靶点,并参与调节神经活性配体-受体相互作用、钙信号通路、5-羟色胺能突触、唾液分泌、间隙连接和脂肪细胞中的脂肪分解6条信号通路。结论本文应用网络药理学方法预测钩藤治疗高血压的潜在药效成分、作用靶点及信号通路,为钩藤治疗高血压的临床应用提供依据。
Objective To determine the mechanism of uncaria rhynchophylla for hypertention based on network pharmacology. Methods Chemical compents with oral bioavailability greater than 30% and druglike properties greater than 0.18 in uncaria rhynchophylla were screened as potential effective ingredients,and targets were searched in the TCMSP database. GeneCards, TTD, and OMIM databases were combined to search for hypertension related targets, while common targets of components and hypertension were extracted as key targets. GO functional enrichment analysis and KEGG pathway enrichment analysis were performed for key targets with CluGO plug-in, and an "ingredient-target-signal pathway" network was constructed. Results Totally 11 components in uncaria rhynchophylla were screened, which acted synergistically on key targets such as PTGS1, PTGS12, CHRM1, ADRα1 B, etc, and participated in 6 signaling pathways of neuroactive ligandreceptor interaction, calcium signaling pathway, serotonergic synapse, salivary secretion, gap junction and regulation of lipolysis in adipocytes. Conclusion Potential effective components, targets and signaling pathways of uncaria rhynchophylla for hypertension are predicted based on network pharmacology, which provides a basis for clinical application of uncaria rhynchophylla for hypertension.
Objective To determine the mechanism of uncaria rhynchophylla for hypertention based on network pharmacology. Methods Chemical compents with oral bioavailability greater than 30% and druglike properties greater than 0.18 in uncaria rhynchophylla were screened as potential effective ingredients,and targets were searched in the TCMSP database. GeneCards, TTD, and OMIM databases were combined to search for hypertension related targets, while common targets of components and hypertension were extracted as key targets. GO functional enrichment analysis and KEGG pathway enrichment analysis were performed for key targets with CluGO plug-in, and an "ingredient-target-signal pathway" network was constructed. Results Totally 11 components in uncaria rhynchophylla were screened, which acted synergistically on key targets such as PTGS1, PTGS12, CHRM1, ADRα1 B, etc, and participated in 6 signaling pathways of neuroactive ligandreceptor interaction, calcium signaling pathway, serotonergic synapse, salivary secretion, gap junction and regulation of lipolysis in adipocytes. Conclusion Potential effective components, targets and signaling pathways of uncaria rhynchophylla for hypertension are predicted based on network pharmacology, which provides a basis for clinical application of uncaria rhynchophylla for hypertension.
引文
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[15]高鹏.炎症反应通路相关基因与脑卒中发病关系的研究[D].长春:吉林大学,2008.
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[18]王振平.大蓟、小蓟水煎剂治疗高血压的比较研究[D].济南:山东大学,2006.
[19]朱华超.针刺对应激性高血压前期大鼠心脏基因表达的影响[D].北京:北京中医药大学,2016.
[2]Carey RM,Whelton PK.Prevention,detection,evaluation,and management of high blood pressure in adults:Synopsis of the 2017 American College of Cardiology/American Heart Association Hypertension Guideline[J].Ann Intern Med,2018,168(5):351-358.
[3]王娟,曹洁,陈宝元.β-受体阻滞剂能否应用于慢性阻塞性肺疾病及支气管哮喘患者[J].中华结核和呼吸杂志,2011,34(4):314-315.
[4]袁千,王凌.中国药典2015年版收载治疗高血压的中成药用药特点研究[J].中国现代应用药学,2017,34(4):530-532.
[5]张振.山楂叶总黄酮对高脂高盐所致高血压大鼠降压及心脏保护作用的研究[J].环球中医药,2017,10(2):136-140.
[6]中国药典2015年版.一部[S].2015:257.
[7]高晓宇,丁茹,王道平,等.钩藤化学成分及药理作用研究进展[J].天津医科大学学报,2017,23(4):380-382.
[8]李泮霖,苏薇薇.网络药理学在中药研究中的最新应用进展[J].中草药,2016,47(16):2938-2942.
[9]Li S,Zhang B.Traditional Chinese medicine network pharmacology:theory,methodology and application[J].Chin J Nat Med,2013,11(2):110-120.
[10]李海燕.基于结构预测药物口服吸收/肝清除及生物利用度[D].沈阳:沈阳药科大学,2009.
[11]Walters JR.New advances in the molecular and cellular biology of the small intestine[J].Curr Opin Gastroen,2002,18(2):161-167.
[12]刘丹,朱靖博,王永华,等.基于网络药理学的银杏叶提取物治疗痛风潜在作用机制初探[J].中草药,2016,47(15):2693-2700.
[13]蔡菲菲,李晓燕,董姝,等.基于网络药理学的茵陈蒿汤“异病同治”研究[J].世界科学技术-中医药现代化,2016,18(9):1507-1514.
[14]龙红萍,蔺晓源,王宇红,等.基于网络药理学研究复方钩藤降压片治疗高血压的作用机制[J].中国中药杂志,2018,43(7):1360-1365.
[15]高鹏.炎症反应通路相关基因与脑卒中发病关系的研究[D].长春:吉林大学,2008.
[16]姜山,方传丰,刘汉文,等.SCN5A基因单核苷酸多态性位点H558R与慢型克山病合并高血压及其心电图特征的相关性研究[J].中华地方病学杂志,2012,31(4):377-380.
[17]刘雅炜.冠心病合并高血压1号染色体高密度扫描易感基因关联分析[D].济南:山东大学,2015.
[18]王振平.大蓟、小蓟水煎剂治疗高血压的比较研究[D].济南:山东大学,2006.
[19]朱华超.针刺对应激性高血压前期大鼠心脏基因表达的影响[D].北京:北京中医药大学,2016.