Objective:To explore the molecular biological mechanism of the"salvia chinensis and radix ranunculi ternati"drug pair in the treatment of lung cancer based on network pharmacology.Methods:Searching the TCMSP...Objective:To explore the molecular biological mechanism of the"salvia chinensis and radix ranunculi ternati"drug pair in the treatment of lung cancer based on network pharmacology.Methods:Searching the TCMSP database and previous literatures to screen the active compounds which resist lung cancer activity in salvia chinensis and radix ranunculi ternati.The candidate compounds were unified in the DrugBank to find the corresponding drug targets which were corrected to the standard gene names by the UniProt database.The Swiss Target Prediction platform was used to predict other targets.Searching GeneCards,OMIM and DrugBank to obtain genes related to lung cancer.After taking the intersection,the candidate gene target of drug pair in the treatment of lung cancer could be obtained.The"herbs-compounds-targets-disease"network was bulit with Cytoscape,and the PPI network was bulit on the STRING platform while the core network nodes were screened.GO and KEGG analysis on candidate genes was implemented through Metacape platform,and a"pathways-targets"network was bulit to further screen key genes.Results:A total of 16 active compounds in salvia chinensis,18 active compounds in radix ranunculi ternati,164 candidate targets,2443 GO functions and 170 KEGG pathways was obtained.Conclusion:The effective compounds of"salvia chinensis and radix ranunculi ternati"drug pair in the treatment of lung cancer are quercetin,ursolic acid,β-sitosterol and caffeic acid.The key targets are MAPK1,AKT1,PIK3R1,RAF1 and EGFR.GO functions mainly include cytokines,oxidative stress,plasma membrane transmission,protein kinase binding and activity,apoptosis.KEGG could directly regulate pathways in cancer,non-small cells lung cancer pathway and small cell lung cancer pathway.KEGG also involves EGFR tyrosine kinase inhibitor resistance,IL-17,TNF,PI3K-AKT signaling pathway and apoptosis.This study reveals the molecular biological mechanism of"salvia chinensis and radix ranunculi ternati"drug pair in the treatment of lung cancer.It is reasoned that its potential targets affect multiple signaling pathways and ultimately resist the proliferation,differentiation,invasion,metastasis and promote apoptosis of lung cancer cells.Evidence for further experimental study is provided by this study.展开更多
[目的]通过对浙江省裘氏妇科流派治疗子宫内膜异位症(endometriosis,EMs)的中医思辨特征、共性规律的研究,总结裘氏妇科诊疗EMs的群体共性规律,并且基于网络药理学研究共性规律中的常用药对的分子机制,以期传承浙派裘氏妇科临证用药经验...[目的]通过对浙江省裘氏妇科流派治疗子宫内膜异位症(endometriosis,EMs)的中医思辨特征、共性规律的研究,总结裘氏妇科诊疗EMs的群体共性规律,并且基于网络药理学研究共性规律中的常用药对的分子机制,以期传承浙派裘氏妇科临证用药经验,提高临床疗效。[方法]临床随诊在省内具有一定影响力的4位裘氏妇科传承人张萍青、吴燕平、王幸儿、张婷,规范采集和录入临床诊疗信息,建立名中医医案数据库,采用聚类分析、关联规则分析等技术,对各名中医的用药特点、辨证规律等进行数据分析挖掘,总结其共性规律。通过中药系统药理学数据库与分析平台(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,TCMSP)挖掘常用药对的活性成分及作用靶标,通过GeneCards数据库挖掘EMs的相关靶点,筛选出常用药对治疗EMs的靶标,利用Cytoscape软件构建活性成分-EMs靶标网络。利用生物学信息注释数据库进行基因本体(gene ontology,GO)生物过程与京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)代谢通路富集分析,预测常用药对治疗EMs的分子机制。[结果]EMs临床常见证型包括瘀热互结证、肾虚血瘀证、气滞血瘀证。针对不同证型,4位医家辨证论治,同中存异,治疗瘀热互结证均以苦寒类的清热药及活血化瘀药为主,治疗肾虚血瘀证使用最多的药物均为补虚药及活血化瘀药,针对气滞血瘀证使用最多的药物均为理气药及活血化瘀药。其中丹参-赤芍药对是裘氏妇科治疗EMs的常用药对,通过TCMSP数据库共筛选出该药对的67种活性成分及78个治疗EMs的靶标,丹参-赤芍药对通过影响信号转导和转录活化因子3(signal transducer and activator of transcription 3,STAT3)、蛋白激酶B1(protein kinase B1,PKB1)、转录因子激活蛋白-1(activator protein-1,AP-1/JUN)、丝裂原活化蛋白激酶1(mitogen activated protein kinase 1,MAPK1)、核转录因子-κB p65(nuclear factor-κB p65,NF-κB p65/RELA)等关键靶点,调控磷脂酰肌醇3-激酶-蛋白激酶B(phosphatidylinositol 3-kinase-protein kinases B,PI3K-PKB)信号通路、白细胞介素-17(interleukin-17,IL-17)信号通路、缺氧诱导因子-1(hypoxia inducible factor-1,HIF-1)信号通路等治疗EMs。[结论]4位裘氏妇科传承人治疗EMs,均以“肾虚”为本,“瘀”“热”互结为标,以苦寒、甘温之品补肾虚、化瘀血、清瘀热、行气滞,且善用药对。丹参-赤芍药对为裘氏妇科的常用药对,与裘笑梅先生清化逐瘀治疗EMs的学术思想相吻合。网络药理学揭示了该药对治疗EMs的分子机制,为进一步药效物质基础分析和分子机制研究提供了依据。展开更多
基金National Natural Science Foundation of China(No.1673961)Beijing Natural Science Foundation Project(No.7172186)Special Training Program for Outstanding Young Scientific and Technological Talents(innovation)of Chinese Academy of Traditional Chinese Medicine(No.ZZ13-YQ-028)。
文摘Objective:To explore the molecular biological mechanism of the"salvia chinensis and radix ranunculi ternati"drug pair in the treatment of lung cancer based on network pharmacology.Methods:Searching the TCMSP database and previous literatures to screen the active compounds which resist lung cancer activity in salvia chinensis and radix ranunculi ternati.The candidate compounds were unified in the DrugBank to find the corresponding drug targets which were corrected to the standard gene names by the UniProt database.The Swiss Target Prediction platform was used to predict other targets.Searching GeneCards,OMIM and DrugBank to obtain genes related to lung cancer.After taking the intersection,the candidate gene target of drug pair in the treatment of lung cancer could be obtained.The"herbs-compounds-targets-disease"network was bulit with Cytoscape,and the PPI network was bulit on the STRING platform while the core network nodes were screened.GO and KEGG analysis on candidate genes was implemented through Metacape platform,and a"pathways-targets"network was bulit to further screen key genes.Results:A total of 16 active compounds in salvia chinensis,18 active compounds in radix ranunculi ternati,164 candidate targets,2443 GO functions and 170 KEGG pathways was obtained.Conclusion:The effective compounds of"salvia chinensis and radix ranunculi ternati"drug pair in the treatment of lung cancer are quercetin,ursolic acid,β-sitosterol and caffeic acid.The key targets are MAPK1,AKT1,PIK3R1,RAF1 and EGFR.GO functions mainly include cytokines,oxidative stress,plasma membrane transmission,protein kinase binding and activity,apoptosis.KEGG could directly regulate pathways in cancer,non-small cells lung cancer pathway and small cell lung cancer pathway.KEGG also involves EGFR tyrosine kinase inhibitor resistance,IL-17,TNF,PI3K-AKT signaling pathway and apoptosis.This study reveals the molecular biological mechanism of"salvia chinensis and radix ranunculi ternati"drug pair in the treatment of lung cancer.It is reasoned that its potential targets affect multiple signaling pathways and ultimately resist the proliferation,differentiation,invasion,metastasis and promote apoptosis of lung cancer cells.Evidence for further experimental study is provided by this study.
文摘[目的]通过对浙江省裘氏妇科流派治疗子宫内膜异位症(endometriosis,EMs)的中医思辨特征、共性规律的研究,总结裘氏妇科诊疗EMs的群体共性规律,并且基于网络药理学研究共性规律中的常用药对的分子机制,以期传承浙派裘氏妇科临证用药经验,提高临床疗效。[方法]临床随诊在省内具有一定影响力的4位裘氏妇科传承人张萍青、吴燕平、王幸儿、张婷,规范采集和录入临床诊疗信息,建立名中医医案数据库,采用聚类分析、关联规则分析等技术,对各名中医的用药特点、辨证规律等进行数据分析挖掘,总结其共性规律。通过中药系统药理学数据库与分析平台(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,TCMSP)挖掘常用药对的活性成分及作用靶标,通过GeneCards数据库挖掘EMs的相关靶点,筛选出常用药对治疗EMs的靶标,利用Cytoscape软件构建活性成分-EMs靶标网络。利用生物学信息注释数据库进行基因本体(gene ontology,GO)生物过程与京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)代谢通路富集分析,预测常用药对治疗EMs的分子机制。[结果]EMs临床常见证型包括瘀热互结证、肾虚血瘀证、气滞血瘀证。针对不同证型,4位医家辨证论治,同中存异,治疗瘀热互结证均以苦寒类的清热药及活血化瘀药为主,治疗肾虚血瘀证使用最多的药物均为补虚药及活血化瘀药,针对气滞血瘀证使用最多的药物均为理气药及活血化瘀药。其中丹参-赤芍药对是裘氏妇科治疗EMs的常用药对,通过TCMSP数据库共筛选出该药对的67种活性成分及78个治疗EMs的靶标,丹参-赤芍药对通过影响信号转导和转录活化因子3(signal transducer and activator of transcription 3,STAT3)、蛋白激酶B1(protein kinase B1,PKB1)、转录因子激活蛋白-1(activator protein-1,AP-1/JUN)、丝裂原活化蛋白激酶1(mitogen activated protein kinase 1,MAPK1)、核转录因子-κB p65(nuclear factor-κB p65,NF-κB p65/RELA)等关键靶点,调控磷脂酰肌醇3-激酶-蛋白激酶B(phosphatidylinositol 3-kinase-protein kinases B,PI3K-PKB)信号通路、白细胞介素-17(interleukin-17,IL-17)信号通路、缺氧诱导因子-1(hypoxia inducible factor-1,HIF-1)信号通路等治疗EMs。[结论]4位裘氏妇科传承人治疗EMs,均以“肾虚”为本,“瘀”“热”互结为标,以苦寒、甘温之品补肾虚、化瘀血、清瘀热、行气滞,且善用药对。丹参-赤芍药对为裘氏妇科的常用药对,与裘笑梅先生清化逐瘀治疗EMs的学术思想相吻合。网络药理学揭示了该药对治疗EMs的分子机制,为进一步药效物质基础分析和分子机制研究提供了依据。
