目的运用网络药理学的分析方法,探讨小儿消积止咳口服液(Pediatric Xiaoji Zhike Oral Liquid,PXZOL)治疗小儿食积咳嗽的功效网络与作用机制。方法通过Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platfo...目的运用网络药理学的分析方法,探讨小儿消积止咳口服液(Pediatric Xiaoji Zhike Oral Liquid,PXZOL)治疗小儿食积咳嗽的功效网络与作用机制。方法通过Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)、Traditional Chinese Medicine Information Database(TCM-ID)等数据库并结合文献,分别搜集PXZOL中药味的主要成分及其作用靶点。利用Comparative Toxicogenomics Database(CTD)、PubMed、Drugbank等数据库并结合文献搜集功能性便秘相关靶点。通过Cytoscape 3.6.0软件构建PXZOL的药味-成分-靶点网络和药物-靶点-疾病的蛋白相互作用(protein-protein interaction network,PPI)网络。通过对PPI网络中靶点进行筛选,构建核心靶点网络。运用ClueGO插件对核心靶点网络进行Gene Ontology(GO)分析和Pathway分析。利用BioGPS数据库对核心靶点进行器官定位。结果GO分析结果显示,PXZOL发挥止咳作用主要是通过调节核转录因子-κB(nuclear transcription factor-κB,NF-κB)信号传导来实现。而发挥消积作用主要是通过相关蛋白质的合成和调节对刺激反应来实现。Pathway分析结果显示,PXZOL发挥止咳作用主要通过丝裂原活化蛋白激酶(mitogen-activatedproteinkinase,MAPK)信号通路、视黄酸(维甲酸)诱导基因蛋白Ⅰ(retinoic acid-inducible gene-Ⅰ,RIG-Ⅰ)样受体信号通路、白细胞介素17(interleukin 17,IL17)信号通路、肿瘤坏死因子受体相关因子6(TNF receptor associated factor 6,TRAF6)介导NF-κB激活等通路。发挥消积作用主要通过多种免疫和炎症信号传导通路来实现。器官定位方面,止咳作用靶点、消积作用靶点以及其共同靶点均有近50%靶点在肺和大肠上有较多表达。结论PXZOL是基于中医"肺与大肠相表里"的理论而组方潜药,现代药理学研究表明发挥"消积止咳"作用多集中在免疫和炎症方面,网络药理学研究发现止咳和消积的作用靶点以及其共同靶点在肺和大肠上有较多表达的数量近50%,从主治疾病和作用网络上提示,PXZOL的疗效发挥是通过黏膜免疫与炎症介导路径来体现中医"肺与大肠相表里"理论的科学性,也为后续在小儿食积咳嗽模型和临床进一步深入研究和验证奠定基础。展开更多
Angelicae Sinensis Radix(Danggui)and Ligusticum Chuanxiong Rhizoma(Chuan Xiong)herb-pair(DC)have been frequently used in Traditional Chinese medicine(TCM)prescriptions for hundreds of years to prevent vascular disease...Angelicae Sinensis Radix(Danggui)and Ligusticum Chuanxiong Rhizoma(Chuan Xiong)herb-pair(DC)have been frequently used in Traditional Chinese medicine(TCM)prescriptions for hundreds of years to prevent vascular diseases and alleviate pain.However,the mechanism of DC herb-pair in the prevention of liver fibrosis development was still unclear.In the present study,the effects and mechanisms of DC herb-pair on liver fibrosis were examined using network pharmacology and mouse fibrotic model.Based on the network pharmacological analysis of 13 bioactive ingredients found in DC,a total of 46 targets and 71 pathways related to anti-fibrosis effects were obtained,which was associated with mitogen-activated protein kinase(MAPK)signal pathway,hepatic inflammation and fibrotic response.Furthermore,this hypothesis was verified using carbon tetrachloride(CCl_4)-induced fibrosis model.Measurement of liver functional enzyme activities and histopathological examination showed that DC dramatically reduced bile acid levels,inflammatory cell infiltration and collagen deposition caused by CCl_4.The increased expression of liver fibrosis markers,such as collagen 1,fibronectin,α-smooth muscle actin(α-SMA)and transforming growth factor-β(TGF-β),and inflammatory factors,such as chemokine(C-C motif)ligand 2(MCP-1),interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α)and IL-6 in fibrotic mice were significantly downregulated by DC herb-pair through regulation of extracellular signal-regulated kinase 1/2(ERK1/2)-protein kinase B(AKT)signaling pathways.Collectively,these results suggest that DC prevents the development of liver fibrosis by inhibiting collagen deposition,decreasing inflammatory reactions and bile acid accumulation,which provides insights into the mechanisms of herbpair in improving liver fibrosis.展开更多
Digestive system cancers,including liver,gastric,colon,esophageal and pancreatic cancers,are the leading cause of cancers with high morbidity and mortality,and the question of their clinical treatment is still open.Pr...Digestive system cancers,including liver,gastric,colon,esophageal and pancreatic cancers,are the leading cause of cancers with high morbidity and mortality,and the question of their clinical treatment is still open.Previous studies have indicated that ZiyuglycosideⅡ(ZYGⅡ),the major bioactive ingredient extract from Sanguisorba officinalis L.,significantly inhibits the growth of various cancer cells.However,the selective anti-tumor effects of ZYGⅡagainst digestive system cancers are not systemically investigated.In this study,we reported the anti-cancer effect of ZYGⅡon esophageal cancer cells(OE21),cholangiocarcinoma cells(Hu CCT1),gastric cancer cells(BGC-823),liver cancer cells(Hep G2),human colonic cancer cells(HCT116),and pancreatic cancer cells(PANC-1).We also found that ZYGⅡinduced cell cycle arrest,oxidative stress and mitochondrial apoptosis.Network pharmacology analysis suggested that UBC,EGFR and IKBKG are predicted targets of ZYGⅡ.EGFR signaling was suggested as the critical pathway underlying the anti-cancer effects of ZYGⅡand both docking simulation and western blot analysis demonstrated that ZYGⅡwas a potential EGFR inhibitor.Furthermore,our results showed synergistic inhibitory effects of ZYGⅡand chemotherapy 5-FU on the growth of cancer cells.In summary,ZYGⅡare effective anti-tumor agents against digestive cancers.Further systemic evaluation of the anti-cancer activities in vitro and in vivo and characterization of underlying mechanism will promote the development of novel supplementary therapeutic strategies based on ZYGⅡfor the treatment of digestive system cancers.展开更多
文摘目的运用网络药理学的分析方法,探讨小儿消积止咳口服液(Pediatric Xiaoji Zhike Oral Liquid,PXZOL)治疗小儿食积咳嗽的功效网络与作用机制。方法通过Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)、Traditional Chinese Medicine Information Database(TCM-ID)等数据库并结合文献,分别搜集PXZOL中药味的主要成分及其作用靶点。利用Comparative Toxicogenomics Database(CTD)、PubMed、Drugbank等数据库并结合文献搜集功能性便秘相关靶点。通过Cytoscape 3.6.0软件构建PXZOL的药味-成分-靶点网络和药物-靶点-疾病的蛋白相互作用(protein-protein interaction network,PPI)网络。通过对PPI网络中靶点进行筛选,构建核心靶点网络。运用ClueGO插件对核心靶点网络进行Gene Ontology(GO)分析和Pathway分析。利用BioGPS数据库对核心靶点进行器官定位。结果GO分析结果显示,PXZOL发挥止咳作用主要是通过调节核转录因子-κB(nuclear transcription factor-κB,NF-κB)信号传导来实现。而发挥消积作用主要是通过相关蛋白质的合成和调节对刺激反应来实现。Pathway分析结果显示,PXZOL发挥止咳作用主要通过丝裂原活化蛋白激酶(mitogen-activatedproteinkinase,MAPK)信号通路、视黄酸(维甲酸)诱导基因蛋白Ⅰ(retinoic acid-inducible gene-Ⅰ,RIG-Ⅰ)样受体信号通路、白细胞介素17(interleukin 17,IL17)信号通路、肿瘤坏死因子受体相关因子6(TNF receptor associated factor 6,TRAF6)介导NF-κB激活等通路。发挥消积作用主要通过多种免疫和炎症信号传导通路来实现。器官定位方面,止咳作用靶点、消积作用靶点以及其共同靶点均有近50%靶点在肺和大肠上有较多表达。结论PXZOL是基于中医"肺与大肠相表里"的理论而组方潜药,现代药理学研究表明发挥"消积止咳"作用多集中在免疫和炎症方面,网络药理学研究发现止咳和消积的作用靶点以及其共同靶点在肺和大肠上有较多表达的数量近50%,从主治疾病和作用网络上提示,PXZOL的疗效发挥是通过黏膜免疫与炎症介导路径来体现中医"肺与大肠相表里"理论的科学性,也为后续在小儿食积咳嗽模型和临床进一步深入研究和验证奠定基础。
基金the National Natural Science Foundation of China(No.82004045)the Beijing Nova Program of Science and Technology(No.Z191100001119088)the Beijing University of Chinese Medicine Specific Grant for“Double Top Construction”(No.1000041510168)。
文摘Angelicae Sinensis Radix(Danggui)and Ligusticum Chuanxiong Rhizoma(Chuan Xiong)herb-pair(DC)have been frequently used in Traditional Chinese medicine(TCM)prescriptions for hundreds of years to prevent vascular diseases and alleviate pain.However,the mechanism of DC herb-pair in the prevention of liver fibrosis development was still unclear.In the present study,the effects and mechanisms of DC herb-pair on liver fibrosis were examined using network pharmacology and mouse fibrotic model.Based on the network pharmacological analysis of 13 bioactive ingredients found in DC,a total of 46 targets and 71 pathways related to anti-fibrosis effects were obtained,which was associated with mitogen-activated protein kinase(MAPK)signal pathway,hepatic inflammation and fibrotic response.Furthermore,this hypothesis was verified using carbon tetrachloride(CCl_4)-induced fibrosis model.Measurement of liver functional enzyme activities and histopathological examination showed that DC dramatically reduced bile acid levels,inflammatory cell infiltration and collagen deposition caused by CCl_4.The increased expression of liver fibrosis markers,such as collagen 1,fibronectin,α-smooth muscle actin(α-SMA)and transforming growth factor-β(TGF-β),and inflammatory factors,such as chemokine(C-C motif)ligand 2(MCP-1),interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α)and IL-6 in fibrotic mice were significantly downregulated by DC herb-pair through regulation of extracellular signal-regulated kinase 1/2(ERK1/2)-protein kinase B(AKT)signaling pathways.Collectively,these results suggest that DC prevents the development of liver fibrosis by inhibiting collagen deposition,decreasing inflammatory reactions and bile acid accumulation,which provides insights into the mechanisms of herbpair in improving liver fibrosis.
基金the grants from Beijing University of Chinese Medicine(Nos.1000041510166 and2020-JYB-ZDGG-038)the National Natural Science Foundation of China(No.81773997)+1 种基金the Shandong Province Key Research Program(2016ZDJS07A21 and 2017CXGC1301)supported by research fund"Traditional Chinese medicine pharmacology and toxicology expert(No.ts201511107)"from Taishan Scholar Project of Shandong Provinceince。
文摘Digestive system cancers,including liver,gastric,colon,esophageal and pancreatic cancers,are the leading cause of cancers with high morbidity and mortality,and the question of their clinical treatment is still open.Previous studies have indicated that ZiyuglycosideⅡ(ZYGⅡ),the major bioactive ingredient extract from Sanguisorba officinalis L.,significantly inhibits the growth of various cancer cells.However,the selective anti-tumor effects of ZYGⅡagainst digestive system cancers are not systemically investigated.In this study,we reported the anti-cancer effect of ZYGⅡon esophageal cancer cells(OE21),cholangiocarcinoma cells(Hu CCT1),gastric cancer cells(BGC-823),liver cancer cells(Hep G2),human colonic cancer cells(HCT116),and pancreatic cancer cells(PANC-1).We also found that ZYGⅡinduced cell cycle arrest,oxidative stress and mitochondrial apoptosis.Network pharmacology analysis suggested that UBC,EGFR and IKBKG are predicted targets of ZYGⅡ.EGFR signaling was suggested as the critical pathway underlying the anti-cancer effects of ZYGⅡand both docking simulation and western blot analysis demonstrated that ZYGⅡwas a potential EGFR inhibitor.Furthermore,our results showed synergistic inhibitory effects of ZYGⅡand chemotherapy 5-FU on the growth of cancer cells.In summary,ZYGⅡare effective anti-tumor agents against digestive cancers.Further systemic evaluation of the anti-cancer activities in vitro and in vivo and characterization of underlying mechanism will promote the development of novel supplementary therapeutic strategies based on ZYGⅡfor the treatment of digestive system cancers.
